Article

Hypofractionated, palliative radiotherapy for advanced head and neck cancer

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Abstract

A significant proportion of advanced stage head and neck cancer patients are incurable and have a limited life expectancy. This study reports a single institution experience with a hypofractionated radiotherapy regimen for palliation of loco-regionally advanced and incurable HNSCC. Between 2000 and 2005, 110 patients of unresectable HNSCC were treated with a palliative radiotherapy (40Gy in 16 fractions). Distressing symptoms were assessed before treatment. Patients with good objective regression with acceptable toxicity received further escalation of dose till 50Gy. We made three strata to compare symptomatic improvement namely percentage relief <50%, between 50-75% and >75% as compared to baseline. Most common baseline distressing complaints were pain in 109 (99%) patients and dysphagia in 97 (88%) patients. Eleven patients (10%) had complete response (CR) and 80 (73%) patients had complete and partial response (PR). At completion of radiotherapy 26%, 57%, and 17% of patients had <50%, 50-75%, and >75% symptomatic relief, respectively. The overall PFS (defined as either complete disappearance of the disease or non-progression in the irradiated field) at 12 months was 55.1% (95% CI, 40.3%-69.9%). On multivariate analysis weight >50kg (p=0.049) and radiotherapy dose of more than 40Gy (p=0.012) were found to be significant for PFS. Acute and late reactions were acceptable. The hypofractionated radiotherapy regimen evaluated is an effective treatment modality for sustained symptoms relief with good response rates and acceptable toxicity.

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... Palliative radiation therapy (RT) is often utilized for these patients to prevent local progression and alleviate symptoms caused by locoregional disease. Several palliative regimens have been studied, including conventional fractionation, hypo-and hyperfractionation, and stereotactic body RT [3][4][5][6][7][8][9][10][11][12][13]. ...
... All statistical analyses were performed using SPSS v23.0 (IBM Corp, Armonk, NY, USA) and R v4.2.2 (R Core Team, R Foundation for Statistical Computing, Vienna, Austria). A total of 70 patients were included for analysis with a median follow-up of 8 Median age at the time of RT was 65.5 years (IQR: 57.9-77.8). Most common primary tumor sites were oropharynx (32.9%), oral cavity (24.3%), and larynx (15.7%). ...
... Median CPS was 17.5 (range: 3-100) in patients with CPS ≥ 1. The median number of ICI cycles was eight (IQR: [4][5][6][7][8][9][10][11][12] in the QS + ICI group. Nineteen patients (27.1%) also received concurrent systemic therapy other than ICIs, which was significantly higher in patients who did not receive concurrent ICIs (50.0% vs. 10.0%, ...
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Simple Summary Immunotherapy represents the standard-of-care systemic therapy in patients with recurrent and metastatic head and neck cancer (HNC). However, these patients often present with local disease, which can affect quality of life, and local progression can lead to significant morbidity. Local response rates from immunotherapy alone are subpar. Thus, palliative radiation is often utilized in this scenario. ‘QuadShot’(QS), a hypofractionated palliative radiation regimen, can provide symptomatic relief and local control and may potentiate the effects of immunotherapy. There have been no previous studies evaluating the combination of immunotherapy with QS. We found that the combination of QS with concurrent immunotherapy was well tolerated and significantly improved local control compared to QS alone. The median survival of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation. Abstract Objectives: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. ‘QuadShot’ (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. Materials and Methods: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. Results: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9–77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60–70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073–0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. Conclusions: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.
... Locoregionally advanced (LA) HNSCC is treated by multimodality approaches combining surgery, radiotherapy and chemotherapy; radio therapy being the main modality for unresctable tumors [5]. Nevertheless, the outcome of conventional radiation was disappointing, especially in advanced stage (i.e., stage III or IV) with a 5-year survival less than 60% only [6,7]. ...
... The patients characteristics were comparable with other studies [5,19]. In this research by study design, PFS was the most common subsite followed by the RMT, Vallecula and BOT. ...
... PFS at the 6 th and 12 th month was 84.6% and 61.5%, respectively. This finding is almost similar with the study by Agarwal JP et al. [5] where 1-year PFS was 55%. Another study by Teckie et al. [21] demonstrated a locoregional PFS rate of 70% at the 6 th month, 43% at the 12 th month, and 29% at the 2 nd year with median follow up of 11.9 months. ...
Article
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Background. Locoregionally advanced head and neck cancers are more aggressive and locoregional failure rate after conventional radiotherapy is high. Objective. The aim of the study is to assess the tumor response and toxicities of hypofractionated radiation therapy with concurrent chemotherapy in treatment of four relatively radioresistent tumor sites of head and neck. Methods. A prospective randomised control trial was conducted in 27 head and neck cancer patients. All patients were treated with hypofractionated radiotherapy at 250cGy/fraction once daily to a maximum of 62.5Gy in 25 fractions with concurrent cisplatin 30 mg/m2. Data were evaluated with SPSS version 21.0 for Windows with p-value <0.05. Results. Complete and partial responses were achieved in 15 (57.7%) and 8 (30.8%) patients respectively with an overall response rate of 88.5% and three patients having stable disease. Grade 3 and 4 acute mucositis was experienced by 17 patients (65.4%) and seven patients (27%), respectively. Grade 3 dysphagia was found in 21 patients (80.7%) and grade 3 and 4 skin reactions – in 11 and 2 patients, respectively. Most patients had manageable acute toxicities. Most of the late complications were of grade 2 and 3. The median time to locoregional recurrence was 12 months and one year progression-free survival attained by 61.5% patients. Conclusion. Treatment with hypofractionated radiotherapy with concurrent cisplatin appears feasible and safe and is associated with a good response rate. Although grade 3 and 4 toxicities were comparatively high but it was manageable. Late toxicities were within tolerable levels.
... Several retrospective studies and prospective single-arm trials have evaluated various regimens of PRT for compromised patients with HNC, including several studies evaluating split-course regimens. [9][10][11] However, there is significant variability in opinions on the best therapeutic option for these patients with no universal consensus. This study examines one such split-course hypofractionated PRT (SPORT) regimen used for HNC patients, exploring its efficacy and tolerability in such clinical settings, and compares it to other regimens reported in the literature. ...
... The acute toxicity associated is usually minimal and easily manageable. [7][8][9][10][11]14 The risks of increased late toxicity due to larger doses per fraction and of increased chances of recurrence due to insufficient total dose can be neglected due to limited life expectancy in this patient group. ...
... 16 Over the last few decades, a myriad variety of dose fractionation schemes have been tried and reported in the literature, with tumour response rates ranging from 53% to 83%. [7][8][9][10][11][17][18][19][20][21][22][23][24][25][26][27][28][29] Table 2 compares some of these PRT schedules with the present study's results. With a tumour response rate of 73% and symptomatic relief in 72% cases, the results are comparable to those that have been reported in previous trials. ...
Article
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Introduction: Head and neck cancers (HNCs) are some of the commonest cases requiring palliative radiotherapy (PRT) in an Indian radiotherapy practice. A variety of PRT protocols have been explored with varying success. Methods: The study objective was to evaluate the efficacy and tolerability of a short-course hypofractionated PRT schedule in HNC patients in terms of symptom relief, tumour response, acute side effects and survival and to compare results with other PRT regimens. All patients received 30 Gy in 10 fractions over 2 weeks followed by another 20 Gy in 5 fractions after a 4 weeks gap. Results: Seventy-five percent of patients completed both phases of treatment. Symptom relief was seen in 71% (pain) to 76% (dysphagia) of patients. Tumour response was recorded in 73% of patients. At 12 months, the mean overall survival was 10·29 months for patients who responded to PRT compared to 7·87 months for those who did not. Results were comparable to other regimens reported in the literature, but no radiobiological advantage of a higher dose was discernible. Conclusions: Short-course hypofractionated PRT is effective in reducing tumour burden and relieving symptoms in HNC patients and possibly in lengthening survival. Selection of any schedule should be decided by treating oncologists based on clinical, logistic and socio-economic factors.
... Its' role in locally advanced head-and-neck carcinoma has been established already by a number of clinical studies. [4][5][6][7][8][9] It is common practice to offer patients curative anti-cancer therapy even in advanced malignancies in the hope that it would maximize local control and cure. However, a significant proportion of these patients default treatment and are noncompliant to such protracted schedules. ...
... [5] The Agarwal et al. study, which used 40 Gy in 16 fractions reported >50% pain improvement in 78% of patients. [6] We identified QOL as the most important endpoint in these group of patients as different schedules have shown little improvement in survival and local control over the years. Since buccal mucosa is the most common subsite of cancer of the oral cavity and forms the major subgroup of patients reporting to our OPD, our focus was on this subgroup of patients. ...
... The three trials closest to ours in terms of total dose and dose per fraction was the Christie trial, the Tata Memorial Hospital (TMH) study and the All India Institute of Medical Sciences (AIIMS) study and had grade 3 mucositis rates of 65%, 66%, and 62%, respectively. [4][5][6] The corresponding grade 3 skin toxicity was 45.14% and 56%, respectively in these three studies. The Christie group in the three arm randomized trial had 53% grade 3 acute mucosal toxicity and 40% grade 3 skin reactions. ...
Article
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Context: The study was designed to evaluate the effect of a hypofractionated, palliative conformal radiotherapy regimen of 5250 cGy in 15 fractions in inoperable/incurable oral cavity carcinoma. Aims: The primary objective was to assess the change in the quality of life (QOL) with respect to pain and mouth opening pre- and post-radiotherapy using standardized questionnaires. The secondary objective was to assess overall QOL using the same questionnaires and also to assess response rates, survival, compliance, early and late toxicity. Settings and design: This was a single-arm, prospective trial. Patients with incurable oral cavity cancer referred for palliative intent radiotherapy to the Department of Radiotherapy, RCC, JIPMER were recruited into the study. Subjects and methods: Forty-eight patients were recruited and twenty-five patients were given conformal radiotherapy to a dose of 52.5 Gy in 15 fractions. QOL was assessed using the European Organization of Research and Treatment of Cancer (EORTC) questionnaires before and 2 months after the completion of radiotherapy. The response assessment was made using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 2 months after radiotherapy. The early and late toxicities were assessed at 2 months and 6 months after radiotherapy completion, respectively. Statistical analysis used: Sample size was calculated to be 53. The Wilcoxon signed-rank test was used to compare QOL scores pre- and post-radiotherapy. Median survival was assessed using the Kaplan-Meier method. Results: There was a significant improvement in the pain, mouth opening, speech, social contact, social eating, felt ill items of the EORTC QLQ-H and N35 questionnaire and role functioning, emotional functioning, social functioning, fatigue, pain, insomnia, appetite loss, financial difficulties, and Global QOL subscales of the QLQ-C30 questionnaire. 72% of the patients had grade 3 acute radiation oral mucositis and 36% had grade 3 acute radiation dermatitis. There were no significant treatment breaks due to toxicity. There were no grade 3 late toxicities observed. Overall median survival was 5.1 months. The overall response rate was 47%. The median time to treatment completion was 24 days. Conclusions: The improvement in QOL parameters suggests that the regimen of 52.5 Gy in 15 fractions is suitable for palliative intent radiotherapy in late-stage oral cavity cancer for effective palliation for short periods.
... Given that there are multiple RT regimens utilized for patients with locally advanced and/or metastatic head and neck cancer ranging from the quad-shot regimen (14-14.8 Gy in 4 twice-daily fractions) (10-12) to moderate hypofractionation (e.g., 55 Gy in 2.5 Gy fractions) (13) to conventionally fractionated definitive-dose regimens, Rades and colleagues (14) developed a palliative scale to better determine their appropriateness based on expected survival. ...
... Based on these survival data, different PRT fractionation schemes were recommended. For patients with the lowest survival (8-9 points), short PRT schemes (e.g., quad-shot, 8 Gy in 1 fraction) should be considered, while for patients with moderate survival (11-13 points), intermediate regimens lasting 1-2 weeks (e.g., 20 Gy in 5 fractions with option to repeat in 2-4 weeks, 36 Gy in 12 fractions) can be considered (13). Patients with the longest expected OS (14-15 points), however, can be considered for a longer, more durable course of RT such as 40-55 Gy in 2-2.5 Gy fractions, or longer, more conventionally fractionated courses. ...
Article
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Background and objective: Palliative radiotherapy (PRT) practice patterns among radiation oncologists are heterogeneous. Appropriate selection of PRT regimen must balance symptom/disease control with patient quality of life. The aim of this review is to summarize prognostic scoring systems for PRT in order to help guide clinical decision making and selection of appropriate PRT regimens. Methods: A PubMed search was conducted for articles published between 01/2000 and 07/2023. Standardized search terms including "palliative", "radiotherapy" and "survival" were used. Only English-language, peerreviewed articles that presented a prognostic scoring system of PRT were included in this review. Key content and findings: In this study, we review the published literature on prognostic scoring systems for patients treated with PRT. Multiple models have been developed and each pertains to a specific patient population or primary tumor type. While they are specific to a particular patient population, all models incorporate patients' clinical characteristics such as primary site, performance status, location of metastatic disease, and indication for PRT to estimate overall survival (OS) after PRT. For each model, the salient points of the scoring system are described. Based on survival estimates from each prognostic system, different PRT regimens are recommended. Conclusions: PRT scoring systems can be used to help clinicians assess patient prognosis. With the information provided by the included studies, radiation oncologists will be better prepared to formulate an optimal, individualized treatment plan for patients to be treated with PRT.
... Survival rates are dismal, around 10 to 40% at 1 year across multiple studies. [8][9][10][11][12][13][14][15][16][17][18] Advanced T stage impairs the ability to attain complete surgical resection with pathologically negative margins in technically unresectable tumors. [19][20][21][22][23] Neoadjuvant chemotherapy (NACT) may cause reduction in the tumor volume, help achieve the balance between radical clearance and surgical morbidity, and may also provide a survival benefit. ...
... Survival rates for such advanced stage IV oral cancers vary widely across studies. [15][16][17][18] In a recent study, Belcher et al reported a 29% 5-year survival rate for this group. 14 Although the results were not widely replicable, a study by Liao et al reported 45% survival at five years in T4b oral cancer treated by surgery. ...
Article
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Background Oral cavity cancers require definitive surgical resection as the primary treatment, but with advanced T stage, complete resection with pathologically negative margins might be difficult to achieve. Induction chemotherapy helps achieve the balance between resection and morbidity in locally advanced technically unresectable tumors. Aim The aim of this study was to analyze the impact of surgery in locally advanced, technically unresectable oral cavity cancers after neoadjuvant chemotherapy (NACT). Materials and Methods A retrospective analysis of patients with borderline resectable, locally advanced oral cavity cancers who were given NACT between February 2017 and December 2021 was conducted. Data regarding clinical and pathological characteristics, NACT, surgery, adjuvant therapy, and recurrences was analyzed. Results Of the 69 patients in the study, 69.6% had tongue cancer, rest were gingivobuccal complex cancers. All tumors were resected based on the post-NACT tumor volume and clear margins were achieved in 42% of cases. About 85.4% of the tongue cancers required a lesser resection than anticipated, thereby following the concept of organ and functional preservation post-NACT as proposed by Licitra et al. About 30.4% had ypT0 and 17.4% had ypN0. Recurrence and survival rates noted in our study were comparable to those reported in literature. Lymph node density of more than or equal to 0.07 was found in all recurrent cases. Conclusions Induction chemotherapy offers a chance of achieving adequate surgical resection while reducing morbidity and improving functional outcomes for patients with technically unresectable oral cavity cancers. Nodal disease may not respond to chemotherapy as well as the primary tumor. There is a need for comprehensive evaluation of prognostic factors, which could help identify the patients who will most benefit with NACT.
... These patients are mostly treated with palliative intent with either radiation or chemotherapy alone or in a concurrent setting. [2,3] Due to the improved surgical expertise and improved outcomes, ITF clearance has become part of the standard treatment. Multiple patterns of spread and outcomes have been described with variable outcomes. ...
... Multiple patterns of spread and outcomes have been described with variable outcomes. [2][3][4][5] In this study, we have highlighted our surgical technique with the oncological outcome of enbloc resection of primary oral cancer involving ITF. ...
Preprint
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Purpose The oral cavity Squamous Cell Carcinoma (OCSCC) involving infratemporal fossa (ITF) is considered as cT4b stage per AJCC 8th classification. The treatment of these group of patients is challenging due to the difficulty in achieving negative resection margin status. In this study we have highlighted our surgical technique with oncological outcome of enbloc resection of primary oral cancer involving ITF. Methodology This was a single centre retrospective study which included only patients with OCSCC extending into ITF. Our surgical technique of systematic “out to in and top to bottom” approach was detailed. The perioperative outcomes, histopathological details, survival outcomes were measured. Results Over the period of 1 year a total of 340 patients with OCSCC reported to our outpatient department, out of which 120 patients belonged to cT4 category and 32 patients were cT4b stage with involvement of ITF. Amongst 32 patients, 2 patients had distant metastasis and were excluded from the study. The 5 patients received neoadjuvant chemotherapy followed by surgery and rest all patients were taken up for upfront curative surgery. There were no significant intraoperative and postoperative complications. None of the margins were found to be involved or close in the final histopathology report. The median DFS and OS were 31 months and 27 months respectively at a median follow up of 29 months. Conclusion Our systematic approach of enbloc resection of primary oral cancer involving ITF is safe and easily reproducible with high rate of negative resection margin status.
... HRT is already a successfully established therapy for localized prostate cancer and is an adjuvant breast cancer treatment (8)(9)(10)(11)(12). Concerning head and neck cancer, some studies have already shown that the use of moderately HRT is feasible in terms of local control and toxicity (13)(14)(15)(16)(17)(18). Based on these encouraging data, we conducted a retrospective study to analyse whether moderate HRT is an appropriate treatment alternative for elderly and frail patients deemed unfit for chemotherapy. ...
... Nevertheless, the OS rates were rather poor. The toxicity was acceptable and quite comparable to the grades of acute toxicity reported in other HRT studies (13,15,16,44,45). Regarding late toxicity, eight patients in the definitive HRT group and seven in the adjuvant HRT group were lost to follow-up due to impaired mobility, frailty, or non-compliance. ...
Article
Background: Comorbidity and frailty are relevant limitations of normofractionated combined radiochemotherapy for squamous cell head and neck cancer (HNSCC), especially in elderly patients. This retrospective study aimed to evaluate the efficacy and toxicity of moderately hypofractionated radiotherapy (HRT) without chemotherapy in patients ineligible for concurrent radiochemotherapy. Patients and methods: Between 2011 and 2018, 51 elderly/frail patients with HNSCC were treated with either definitive (n=23) or adjuvant (n=28) moderate HRT. A dose of 45 Gy was given to the primary tumour region and cervical nodes with a sequential boost up to 50 in the adjuvant and 55 Gy in the definitive cure setting (2.5 Gy/fraction). Patient outcomes of locoregional control, overall survival, and acute and late toxicity were analysed. Results: After a median follow-up of 6 months for the definitive HRT group and 28.5 months for the adjuvant HRT group, we found a median overall survival of 6 vs. 55 months (log-rank test: p<0.001) and a median locoregional control of 9 months vs. not reached (log-rank test: p=0.008), respectively. The 2-year rates of locoregional control were 28.5% for the definitive HRT group vs. 75.2% for the adjuvant HRT group. No acute or late grade 4-5 toxicity occurred; grade 3 toxicity was rarely documented. Conclusion: HRT in elderly/frail patients with HNSCC who are unfit for chemotherapy leads to acceptable local control with moderate toxicity in a short overall treatment time. Especially in the postoperative situation, HRT can be considered an appropriate alternative to normofractionated radio(chemo)therapy. Definitive HRT can be a treatment alternative, especially for multimorbid patients.
... Split course radiation therapy (SCRT) allows for the titration of treatment intensity based on patient tolerance and disease response (4)(5)(6). In this treatment paradigm, RT is split into two courses, generally 1-2.5 weeks in length, separated by a 4-6-week treatment break. ...
... Normal tissue recovery also occurs during this break, resulting in lower rates of acute grade ≥3 toxicities of 41-53% (7,8), which may allow these patients to receive a traditional cumulative dose of 60-70 Gray (Gy) that they otherwise could not tolerate if delivered continuously. However, treatment breaks may also allow for accelerated repopulation of the malignant cells, potentially reducing efficacy of treatment and highlighting the need for appropriate patient selection (4,5,9). Additionally, hypofractionation of each treatment course could potentially increase late radiation effects. ...
Article
Background/aim: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique. Patients and methods: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported. Results: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively. Conclusion: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT.
... As there is no standard schedule for palliative radiotherapy in LAHNC various palliative schedules have been tried ranging from 20Gy in 5fractions to 40-50Gy in 10 to 15fractions which had variable tumor response and radiation reactions. 7,8 Similar studies had shown that in LAHNC, palliative radiotherapy can achieve 70-80% local tumor control at the end of treatment and 20-30% patients with no clinical disease with less than 10% severe late radiation reactions at the end of 6months follow up. 4,[8][9][10] In this present study complete local response at the end of treatment was better in group I than group II (13.2% vs 3.3%). ...
... 7,8 Similar studies had shown that in LAHNC, palliative radiotherapy can achieve 70-80% local tumor control at the end of treatment and 20-30% patients with no clinical disease with less than 10% severe late radiation reactions at the end of 6months follow up. 4,[8][9][10] In this present study complete local response at the end of treatment was better in group I than group II (13.2% vs 3.3%). Partial response at the end of treatment was more in group II (84%) compared to 74% in group I. Acute grade 3 skin reactions was only seen in 1-patient of group II whereas grade 3 mucosal reactions was seen in 20% patients in group I and 7% in group II. ...
Article
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Background and Aims: Head and neck cancer accounts for 4.8% of all cancers globally and 13.9% of all cancers in India.1 In Indian setting, more than 70% patients present in locally advanced stage and with poor general condition and are suitable candidates for palliative radiotherapy. The present prospective, randomized study was planned to comparatively evaluate the efficacy, tolerability and toxicity of two schedules of palliative radiotherapy in patients of locally advanced head & neck cancer (LAHNC). Methods: The present study was carried out on histopathological proven and inoperable 60-patients of LAHNC. Patients in group I received total external radiation dose of 40Gy, 4Gy/fraction, and 2fractions a week for 5weeks. Group II patients received 20Gy in 5fractions in 5days followed by 3week gap followed by 20Gy in 5fractions in 5days. The groups were compared in terms of local tumor control and adverse effects of radiation. Results: All patients were of stage IV and 83% had nodal involvement. At the end of treatment for local disease, complete response (CR) in group I was better than group II (13.2% vs 3.3%) and complete nodal response was seen in 17% patients in each group. Disease status at 6months of follow up was 27% vs 23% complete tumor response and 30% vs 24% complete nodal response in group I and II respectively. Overall no evidence of disease (NED) was seen in 13% in group I and 17% in group II. Grade 3 skin radiation reactions were only seen in 1-patient of group II, however, grade 3 mucosal radiation reactions were seen in 20% patients in group I and 7% in group II. Seven patients in group I required nasogastric feeding tube as compared to 3-patients in group II. Grade 3 subcutaneous toxicity was equally present in 3% in each group. Conclusions: In this study we observed that both the schedules of radiotherapy are equally effective in tumor control and have comparable toxicity profile. Hence, to decrease the patient load in tertiary care institutes, it is recommended to use fractionation schedule with two radiotherapy fractions per week. Keywords: head and neck cancer, palliative
... In an effort to reduce such early mucosal toxicity, groups have studied the use of smaller fractions with similar cumulative doses. 28,29 ...
... The Tata Group has reported on the delivery of 4000 cGy in 250-cGy fractions to 110 patients with incurable disease and limited life expectancy. 28 The most common baseline symptoms in this cohort were pain (99%) and dysphagia (88%). Seventy-three percent of patients had an objective response, and 74% of patients had >50% symptom relief. ...
Article
Patients with advanced head and neck cancers who are not eligible for curative treatment represent a challenging cohort of patients to manage given the complexity and severity of their presenting symptoms. Palliative radiation therapy, along with other systemic and surgical measures, has the potential to significantly improve the quality of life of such patients. There is little high-level evidence and a lack of consensus to direct the selection of an optimal palliative radiation regimen. An ideal palliative radiation regimen should alleviate symptoms secondary to the cancer with minimal treatment toxicity and side effects while improving a patient's quality of life. This review presents the treatment approaches, outcomes, and toxicities associated with different radiation regimens and proposes a multidisciplinary framework for the selection of an individualized treatment regimen for patients that centers around patient prognosis, goals of care, logistics of treatment, and the availability of other surgical and systemic therapies.
... As there is no standard schedule for palliative radiotherapy in LAHNC various palliative schedules have been tried ranging from 20Gy in 5fractions to 40-50Gy in 10 to 15fractions which had variable tumor response and radiation reactions. 7,8 Similar studies had shown that in LAHNC, palliative radiotherapy can achieve 70-80% local tumor control at the end of treatment and 20-30% patients with no clinical disease with less than 10% severe late radiation reactions at the end of 6months follow up. 4,[8][9][10] In this present study complete local response at the end of treatment was better in group I than group II (13.2% vs 3.3%). ...
... 7,8 Similar studies had shown that in LAHNC, palliative radiotherapy can achieve 70-80% local tumor control at the end of treatment and 20-30% patients with no clinical disease with less than 10% severe late radiation reactions at the end of 6months follow up. 4,[8][9][10] In this present study complete local response at the end of treatment was better in group I than group II (13.2% vs 3.3%). Partial response at the end of treatment was more in group II (84%) compared to 74% in group I. Acute grade 3 skin reactions was only seen in 1-patient of group II whereas grade 3 mucosal reactions was seen in 20% patients in group I and 7% in group II. ...
Article
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Background and Aims: Head and neck cancer accounts for 4.8% of all cancers globally and 13.9% of all cancers in India.1 In Indian setting, more than 70% patients present in locally advanced stage and with poor general condition and are suitable candidates for palliative radiotherapy. The present prospective, randomized study was planned to comparatively evaluate the efficacy, tolerability and toxicity of two schedules of palliative radiotherapy in patients of locally advanced head & neck cancer (LAHNC). Methods: The present study was carried out on histopathological proven and inoperable 60-patients of LAHNC. Patients in group I received total external radiation dose of 40Gy, 4Gy/fraction, and 2fractions a week for 5weeks. Group II patients received 20Gy in 5fractions in 5days followed by 3week gap followed by 20Gy in 5fractions in 5days. The groups were compared in terms of local tumor control and adverse effects of radiation. Results: All patients were of stage IV and 83% had nodal involvement. At the end of treatment for local disease, complete response (CR) in group I was better than group II (13.2% vs 3.3%) and complete nodal response was seen in 17% patients in each group. Disease status at 6months of follow up was 27% vs 23% complete tumor response and 30% vs 24% complete nodal response in group I and II respectively. Overall no evidence of disease (NED) was seen in 13% in group I and 17% in group II. Grade 3 skin radiation reactions were only seen in 1-patient of group II, however, grade 3 mucosal radiation reactions were seen in 20% patients in group I and 7% in group II. Seven patients in group I required nasogastric feeding tube as compared to 3-patients in group II. Grade 3 subcutaneous toxicity was equally present in 3% in each group. Conclusions: In this study we observed that both the schedules of radiotherapy are equally effective in tumor control and have comparable toxicity profile. Hence, to decrease the patient load in tertiary care institutes, it is recommended to use fractionation schedule with two radiotherapy fractions per week.
... For instance, similar outcomes were reported by Talha et al., who observed excellent pain control using a comparable protocol (7). Corry et al. also found significant pain relief in patients with advanced head and neck cancer treated with the "Quad Shot" RT protocol, underscoring the reproducibility of these results across different studies (9). Furthermore, Mohanti et al. reported a partial response rate of 37% in patients with advanced head and neck cancer treated with an RT protocol of 20 Gy delivered in 5 fractions of 4 Gy each over one week (10), while Vargas A. documented significant symptom alleviation in patients with soft tissue tumors treated with a single fraction of RT (11). ...
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Background: Palliative radiation therapy (RT) is increasingly recognized as a crucial component of care for patients with advanced, incurable malignancies. In Pakistan, where patients often present at advanced stages due to socio-economic barriers and limited healthcare access, efficient and effective treatment protocols are essential. Objective: This study aimed to evaluate the efficacy of the Quad Shot hypo-fractionated RT protocol for pain palliation in elderly and frail patients with recurrent or metastatic non-osseous malignancies. Methods: A quasi-experimental study was conducted at the Oncology Department of Ganga Ram Hospital, Lahore. Forty-two elderly patients with histologically confirmed inoperable malignancies and a WHO Performance Status of 2 to 3 were enrolled. Patients with prior RT or a second cancer were excluded. RT was delivered using a Cobalt-60 beam, with a total dose of 14 Gy divided into four fractions over two consecutive days. Pain severity was assessed using a 10-point scale before and four weeks after treatment. Statistical analysis was performed using the Wilcoxon Sign Rank Test on SPSS version 25.0. Results: The study population comprised 52% males and 48% females, with the majority of primary tumors located in the head and neck (64%). Post-treatment, the mean pain score significantly decreased from 8.04 ± 1.22 to 4.32 ± 0.89 (p < 0.05). Conclusion: The Quad Shot hypo-fractionated RT protocol effectively reduces pain in elderly and frail patients with advanced malignancies, suggesting its suitability as a quick and effective palliative care option in resource-limited settings.
... 5,11,12 Increasing doses beyond a biologically effective dose (BED) of 50 Gy was associated with an increase in acute toxicities, mucositis, and dysphagia with subsequent treatment discontinuation. 13,14 Providing the treatments in courses, with gaps allowing for mucosal cell repopulation and repair, offers an alternate way to escalate BED to more than 50 Gy. 7 Table 3 summarizes some of the palliative regimens for head and neck cancer and the present study. ...
Article
Background This study assessed a palliative radiotherapy regimen using daily radiation over 4 days for three courses in inoperable head and neck cancers, emphasizing oral primary cancers. Methods Retrospective data of 116 patients treated with a daily dose of 3.6–3.7 Gy in four fractions over 4 days to a total of three courses, with a 2‐week gap after every course, were analyzed for survival outcomes. A subgroup analysis was done for oral cancer. Results Ninety‐nine (85%) completed three courses. Overall subjective response rate was 77%. Median overall survival and progression‐free survival were 12 months (95% confidence interval [CI]: 8–20) and 8 months (95% CI: 6–10), with numerically higher overall survival in oral cancer. The treatment was well tolerated, with no on‐treatment hospitalization or grade 3–4 toxicities. Conclusion The modified QUAD SHOT regimen is practical for palliation in head and neck cancers.
... Radiotherapy to local site given in 9.6% of multiple myeloma cases, 12.7% cases of head and neck region, 2% cases of the lung cancer, mediastinal tumours, carcinoma cervix, carcinoma urinary bladder, bone tumours, sarcomas, GIT tumours.Genito urinary cancer study done by Sharma., et al. shown most common cancer of head and neck (60%) area followed by gastro Palliation of these patients for relieving symptoms like painful ulcer, throat pain dysphasia and breathing difficulty with minimal toxicities. In India improvement in quality of life and cost benefit issues are more considerable than increases in life expectancy[12]. ...
... Pooling the data from 24 studies with 1,168 patients, the cumulative effect for ORR was 72% (95% CI: 60-80%) (Fig. 2B). Evaluating the cumulative effect over time, the OS changed significantly after the publi-cation of Agarwal et al., and achieved stability from 2010 onwards after the publication of Nguyen et al. (Fig. 2A) [22,32]. The PFS remained inside of 95% CI; after the publication of Kumar et al. in 2015, the PFS achieved stability, (Fig. 2C) [33]. ...
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Background: The objective to assess the outcomes from different palliative radiotherapy (RT) schedules in incurable head and neck cancer (HNC), to evaluate if there is a relationship between RT dose, technique, and fractionation with tumor response in contrast to the occurrence of adverse effects. Materials and methods: Eligible studies were identified on Medline, Embase, the Cochrane Library, and annual meetings proceedings through June 2020. Following PRISMA and MOOSE guidelines, a cumulative meta-analysis of studies for overall response rate (ORR), overall survival (OS), progression-free survival (PFS), pain/dysphagia relief, and toxicity was performed. A meta-regression analysis was done to assess if there is a connection between RT dose, schedule, and technique with ORR. Results: Twenty-eight studies with 1,986 patients treated with palliative RT due to incurable HNC were included. The median OS was 6.5 months [95% confidence interval (CI): 5.6-7.4], and PFS was 3.6 months (95% CI: 2.7-4.3). The ORR, pain and dysphagia relief rates were 72% (95% CI: 0.6-0.8), 83% (95% CI: 52-100%), and 75% (95% CI: 52-100%), respectively. Conventional radiotherapy (2D-RT) or conformational radiotherapy (3D-RT) use were significantly associated with a higher acute toxicity rate (grade ≥ 3) than intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). On meta-regression analyses, the total biological effective doses (BED) of RT (p = 0.001), BED > 60 Gy10 (p = 0.001), short course (p = 0.01) and SBRT (p = 0.02) were associated with a superior ORR. Conclusions: Palliative RT achieves tumor response and symptom relief in incurable HNC patients. Short course RT of BED > 60 Gy using IMRT could improve its therapeutic ratio. SBRT should be considered when available.
... The "QUAD SHOT regimen", that consisted of 3.7 Gy in four fractions given twice a day for 2 consecutive days in order to achieve a total of 44.4 Gy in 12 fractions, impacted positively on clinical outcomes, overall tumor response rate, and symptom relief in 50-70% of patients, with minimal toxicity [67]. Moreover Agarwal et al. proposed a dose-intensive palliative RT regimen of 40 Gy in 16 fractions, obtaining a treatment response rate and symptom relief of about 75%; therefore, as a palliative treatment, a higher dose of hRT may be proposed with positive outcomes [68]. ...
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The abscopal effect (AbE) is defined as radiation-induced shrinkage of distant, non-treated, neoplastic lesions and it is considered the best clinical picture of the efficient immune stimulation by irradiation. The first report about abscopal tumor regression upon radiotherapy dates back to the beginning of the 20th century. The growing preclinical and clinical synergism between radiation and immunotherapy gave birth the purpose to more easily reproduce the abscopal effect, nevertheless, it is still rare in clinical practice. In this review we summarize immunological modulation of radiotherapy, focusing on the well-balanced equilibrium of tumor microenvironment and how radio-immunotherapy combinations can perturb it, with particular attention on head and neck squamous cell cancer. Finally, we investigate future perspectives, with the aim to “tailor” the abscopal effect to the patient.
... However, older (age >60 years) patients with LAHNC with poor performance status (ECOG score of -2 or greater ) with uncontrolled severe comorbidities or poor nutritional status (body mass index <18.5 kg/ m 2 ) are frequently considered unsuitable for the 3-drug NACT regimen. [27][28][29][30] In the present study, close to 42% of the cohort was deemed unfit to receive the 2-drug or 3-drug NACT regimen for the aforementioned reasons. These patients received a median of 3 cycles of a combination of paclitaxel and carboplatin. ...
Article
Objective A prospective, longitudinal assessment of oral and dental health status was done, from baseline until treatment completion, in patients scheduled to receive neo-adjuvant chemotherapy (NACT) for locally-advanced head and neck cancer (LAHNC). Methodology One hundred fifty consecutive, treatment-naïve adult patients with biopsy-proven LAHNC, scheduled to receive NACT, were recruited. One hundred thirty-five patients completed all assessments at 3 designated time points viz. baseline (T0), mid-treatment (T1) and post-treatment (T2). Variables assessed were: Oral Hygiene Index-Simplified (OHI-S), Decayed Missing Filled Teeth Index (DMFT), mucositis grade, pain score and grade of trismus. Results Median OHI-S scores showed a statistically significant increase (higher the score, poorer the oral hygiene) when the patients were evaluated from baseline to completion of NACT (T1 vs. T2; T0 vs. T2 p<0.001) which indicated a decrease in oral health. There was no change in median DMFT score (p=0.32) but a significant change was seen in all-grade mucositis over time (p<0.001). Median pain scores and trismus grade decreased significantly (p<0.001) over time. Conclusion There was a decrease in oral health status without any change in dental health seen in patients undergoing NACT. Mucositis was initially noted as an aftermath of chemotherapy which resolved with time.
... The 3 levels of pain relief were defined as percentage relief <30%, percentage relief 30-70%, and percentage relief >70%, respectively. 18,19 After initial treatment, the patients underwent routine follow-up, including physical examination, laboratory tests, and abdominopelvic radiography every 3 months for the first 2 years and every 6 months thereafter. Colonovideoscopic examinations were conducted 1 year after treatment and then once every 2 years. ...
Article
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Purpose Retroperitoneal lymph node metastases are rare in colorectal cancer. Optimal treatment strategies are still unknown. Patients and Methods We retrospectively enrolled colorectal cancer patients who had received radiotherapy for retroperitoneal lymph node metastases from 2009 to 2018. Patients with isolated retroperitoneal lymph node metastases or retroperitoneal lymph nodes with extra-retroperitoneal metastases were all included. A median dose of 60 Gy was delivered. Results A total of 68 patients were enrolled in this study; 28 (41%) of them had extra-retroperitoneal metastases. In the isolated retroperitoneal lymph node metastases group, complete response was found in 5 patients (12.5%), partial response was achieved in 20 patients (50%), 9 patients (22.5%) had stable disease. The 1-, 2- and 3-year local control rates were 87.5%, 77.5%, and 70%. In the extra-retroperitoneal metastases group, the disease control rate was 75%, including complete response in 1 patient (3.6%), partial response in 4 patients (14.3%) and stable disease in 16 patients (57.1%). The 1-, 2- and 3-year local control rates were 57.1%, 42.8%, and 0%. The median overall survival was 59.4 months and 19 months in the isolated retroperitoneal lymph node metastases group and extra-retroperitoneal metastases group, respectively. In the isolated retroperitoneal lymph node metastases group, the 1-year and 3-year overall survival values were 90.2% and 75.8%, respectively. The 1-year and 3-year progression-free survival values were 57.9% and 0%, respectively. The extra-retroperitoneal metastases group experienced worse survival outcome (1-year overall survival: 57.9%, P<0.05; and 1-year progression-free survival: 22.5%, P<0.05). Conclusion For patients with isolated retroperitoneal lymph node metastases, radiotherapy combined with systemic treatment can be used as a method to achieve no evidence of disease and can result in good local control and survival. For patients with extra-retroperitoneal metastases, although the survival is much worse than that of isolated retroperitoneal lymph node metastases, radiotherapy is an effective palliative treatment to relieve pain and obstruction based on systemic treatment.
... A large retrospective series from India that included 352 patients, used a palliative radiation regimen of 20Gy in 5 fractions; it showed significant palliation of symptoms in 60% of patients [17]. Another large institutional study from Tata Memorial Hospital in India evaluated a hypofractionated palliative radiation scheme: 40Gy in 16 daily fractions (2.5Gy daily) [18]. The patients with any response after 40Gy received an additional 10Gy in 4 fractions to a total dose of 50Gy; only 25% of patients were able to receive the additional 10Gy, but 87% of all patients (either 40 or 50Gy) had symptomatic improvement. ...
Article
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Currently, there are no evidence-based guidelines regarding palliative radiation for untreated head and neck squamous cell carcinoma (HNSCC) patients who are ineligible for curative treatment. This article reviews the available literature for palliative head and neck radiotherapy. The life expectancy and performance status of patients are used to optimize the treatment recommendations.
... Traditionally, T4b cancers of oral cavity are deemed inoperable. These patients are treated with palliative intent with radiation and chemotherapy either alone or in combination [8,9]. The surgery is a viable option though is not fully explored owing to difficulty to achieve clear margins and intricate anatomy of the region. ...
Article
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T4 b carcinoma of oral cavity has poor outcomes. The aim for analysis is to evaluate the clinical outcomes with infratemporal fossa clearance for stage T4b carcinoma of oral cavity. Fifty four patients out of maintained data of 528 patients of oral cavity carcinoma were evaluated for current retrospective analysis. All had T4b disease on imaging and underwent bite composite resection with ITF clearance. The median age of the cohort was 52 years. At last follow-up, 28 patients were alive. Twenty two patients had loco-regional recurrence (ITF recurrence 7), and 16 patients had distant metastasis.At median follow-up of 29 months, 2-year loco-regional control, DFS and OS were 52%, 54% and 54%, respectively. Perineural invasion, pathological tumour stage, node positive and ITF tissue involvement were associated with poor oncological outcomes. ITF clearance is feasible in clinical practice and provides curative option for this group.
... Given the generally dismal outcomes and importance of treatment efficiency for such frail and symptomatic patients, a variety of hypofractionated fractionation schemes have been successfully employed in palliative setting (ranging from 2.5-8 Gy per fraction, to total doses of 14-70Gy). [9][10][11][12][13][14][15][16][17] Studies have reported that the Quad Shot (QS) regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, for up to 4 cycles) may offer the best balance between palliation, toxicity, and convenience. 9,[18][19][20][21] Our prior studies have shown that QS RT with either photon or proton therapy achieves excellent palliative responses (65-73%) and median survival in the 5.7-9.0 month range with minimal toxicity. ...
Article
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Objectives Patients with prior irradiated head and neck cancer (HNC) who are ineligible for definitive retreatment have limited local palliative options. We report the largest series of the use of the Quad Shot (QS) regimen as a last-line local palliative therapy. Materials and Methods We identified 166 patients with prior HN radiation therapy (RT) treated with QS regimen (3.7 Gy twice daily over 2 consecutive days at 4 weeks intervals per cycle, up to 4 cycles). Palliative response defined by symptom(s) relief or radiographic tumor reduction, locoregional progression free survival (LPFS), overall survival (OS) and radiation-related toxicity were assessed. Results Median age was 66 years. Median follow-up for all patients was 6.0 months and 9.7 months for living patients. Overall palliative response rate was 66% and symptoms improved in 60% of all patients. Predictors of palliative response were > 2 year interval from prior RT and 3–4 QS cycles. Median LPFS was 5.1 months with 1-year LPFS 17.7%, and median OS was 6.4 months with 1-year OS 25.3%. On multivariate analysis, proton RT, KPS > 70, presence of palliative response and 3–4 QS cycles were associated with improved LPFS and improved OS. The overall Grade 3 toxicity rate was 10.8% (n = 18). No Grade 4–5 toxicities were observed. Conclusion Palliative QS is an effective last-line local therapy with minimal toxicity in patients with previously irradiated HNC. The administration of 3–4 QS cycles predicts palliative response, improved PFS, and improved OS. KPS > 70 and proton therapy are associated with survival improvements.
... A study from Rajasthan [21] demonstrated symptom relief in >65% of patients with 20 Gy/5#/5 days; almost all patients developed Grade 1 or 2 skin and mucosal toxicities. Agarwal et al. [11] used a schedule of 40 Gy in 16 fractions reported from Mumbai. Patients with PR had a dose escalation up to 50 Gy in 20 fractions. ...
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Context: A significant number of patients with head-and-neck cancers have an incurable disease with limited life expectancy. The objective of the present study was to compare two different short courses of hypofractionated palliative radiotherapy regimens to evaluate symptoms, disease response, and acute toxicity. Materials and methods: Previously untreated 50 patients of Stage IV B and IV C head and neck cancers were randomized to receive conventional hypofractionated palliative radiotherapy 30 Gy/10 fractions/2 weeks (control group) or Quad Shot regimen (study group) 14 Gy in 4 fractions given twice a day at least 6 h apart for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumor progression. Results: Symptom relief was similar among the two schedules for pain (60.86 vs. 57.17), dysphagia (60.86 vs. 52.17%), and hoarseness (43.85 vs. 38.09%). Overall response (that is partial response and stable disease) was seen in majority (>70%) of the patients in both the groups. Treatment was very well tolerated with no patient experiencing more than Grade 3 toxicity in the control group and Grade 2 toxicity in the study group. Conclusions: Quad Shot regimen is an effective hypofractionated palliative radiotherapy schedule with minimal toxicity, good symptom relief, and response rate as compared to conventionally used regimen (30 Gy/10 fractions/2 weeks).
... Currently, there is no consensus regarding radiation regimens or dose in the setting of metastatic SCCHN. A few phase II studies and several retrospective studies have explored the optimal treatment for such patients 5, [18][19][20][21][22][23][24][25][26][27][28]. Most of these studies have included patients with newly diagnosed disease who were ineligible for curative treatment due to comorbid conditions, poor performance status, and metastatic disease at diagnosis. ...
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Background The purpose of this study was to explore the feasibility and tolerability of delivering standard dose chemoradiation therapy to patients with oligo-metastatic squamous cell carcinoma of the mucosal surfaces of the head and neck (Stage IV C) and to evaluate their survival outcomes. Methods We retrospectively analyzed 10 well-performing patients with newly diagnosed oligo-metastatic carcinoma who underwent concurrent chemoradiation to a dose of 70 Gy. Overall survival curves were generated using the Kaplan-Meier method. Results All patients completed their chemoradiation treatment; mean radiation duration was 53 days. Only 10% experienced Grade 3 or higher toxicity. The median overall survival was 12.5 months. Conclusion Well-performing head and neck cancer patients with oligo-metastatic disease who were treated aggressively, tolerated their treatment with acceptable morbidity and had improved survival compared to historical controls.
Article
This review article explores the critical role of time in external radiotherapy, focusing on the concepts of fractionation and spreading. It traces the evolution of radiobiology, highlighting key milestones that have shaped current treatment strategies. The article delves into the four fundamental principles of radiobiology—Repair, Redistribution, Reoxygenation, and Repopulation—and their implications for fractionated radiation therapy. It further discusses the clinical applications of these principles, including hyperfractionated, accelerated, and hypofractionated treatments. This review provides a comprehensive understanding of how the time factor influences the effectiveness of radiotherapy and its impact on healthy and tumor tissues.
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Objective: The aim of the study was to study palliation of symptoms and improvements in quality of life (QoL) in inoperable squamous cell cancers of the oral cavity with a hypofractionated radiotherapy schedule. Methods: It is a prospective and observational study in patients with locally advanced squamous cell cancers of the oral cavity attending the outpatient clinic who have been deemed inoperable after discussion in a multidisciplinary team were considered. The data was tested using Friedman’s test for the significance in QoL. Results: All of the functional scales were found significant in this study with physical functioning, emotional functioning and cognitive functioning (CF) being significant at 1% alpha level while role functioning (RF) and social functioning (SF) are significant at 5% alpha level. RF was assessed based on the capabilities of the patient to finish daily activities. The median score remained at 33 but the interquartile range (IQR) was showing an increasing trend. Both pain and head-and-neck specific pain had significantly reduced over time. Fatigue had shown a constant reduction during radiation and during the first follow-up as well. The increase in nausea, vomiting, and constipation during radiation can be attributed to the use of morphine during radiation for pain control and as an effect of radiation itself. There was weight loss during radiation which improved during subsequent follow-up visits. Conclusions: In patients diagnosed with inoperable oral cavity cancer, hypofractionated radiotherapy delivering 50 Gy in 20 fractions over 4 weeks is a well-tolerated and safe regimen. In our study, statistically significant QoL improvement in global health score, SF, and CF lasting for a minimum of 6 weeks was attained after completion of treatment with this regimen.
Article
Aim and introduction: The oral cavity Squamous Cell Carcinoma (OCSCC) involving infratemporal fossa (ITF) is considered as cT4b stage per AJCC 8th classification. The treatment of these group of patients is challenging due to the difficulty in achieving negative resection margin status. In this study we have highlighted our surgical technique with oncological outcome of enbloc resection of primary oral cancer involving ITF. Methodology: - This was a single centre retrospective study which included only patients with OCSCC extending into ITF. Our surgical technique of systematic "out to in and top to bottom" approach was detailed. The perioperative outcomes, histopathological details, survival outcomes were measured. Results: - Over the period of 1 year a total of 340 patients with OCSCC reported to our outpatient department, out of which 120 patients belonged to cT4 category and 32 patients were cT4b stage with involvement of ITF. Amongst 32 patients, 2 patients had distant metastasis and were excluded from the study. The 5 patients received neoadjuvant chemotherapy followed by surgery and rest all patients were taken up for upfront curative surgery. There were no significant intraoperative and postoperative complications. None of the margins were found to be involved or close in the final histopathology report. The median DFS and OS were 31 months and 27 months respectively at a median follow up of 29 months. Conclusion: - Our systematic approach of enbloc resection of primary oral cancer involving ITF is safe and easily reproducible with high rate of negative resection margin status.
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Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharynx with a unique geographic distribution, and is particularly prevalent in East and Southeast Asia. Due to its anatomical location, the surgery is difficult to access and the high sensitivity of nasopharyngeal cancer to radiotherapy (RT) makes it the main treatment modality. Radical radiotherapy is the first-line treatment for early-stage nasopharyngeal carcinoma and the cornerstone of multidisciplinary treatment for patients with locally advanced nasopharyngeal carcinoma. Nevertheless, radiotherapy interruption is inevitable as a consequence of unavoidable factors such as public holidays, machine malfunction, patient compliance, and adverse response to treatment, which in turn leads to a reduction in bioactivity and causes sublethal loss of tumor cells to repair. Unirradiated tumor cells are more likely to repopulate at or near their original fastest growth rate during this interval. If no measures are taken after the radiotherapy interruption, such as increasing the dose of radiotherapy and systemic therapy, the tumor is most likely to go uncontrolled and then progress. This review describes the effects of radiotherapy interruption on nasopharyngeal carcinoma, the mechanism of the effect, and explores the measures that can be taken in response to such interruption.
Article
Purpose: Locoregionally recurrent head and neck cancer is a complex clinical scenario that often requires multimodality treatment. These patients have often previously received definitive treatment with a combination of surgery, radiation therapy, and systemic therapy, which can make further management difficult. A second isolated locoregional failure is rare and clinicians are faced with a challenge to optimize disease control while minimizing treatment-related toxicity. Methods and materials: In this report, we present the diagnosis, management, and outcomes of a patient with an isolated locoregional recurrence who was previously treated with two courses of radiation. The patient was treated with a second course of reirradiation using interstitial brachytherapy as well as a discussion regarding patient selection and optimal management for recurrent head and neck cancer. Results: Repeat reirradiation using interstitial HDR-brachytherapy with the use of an alloderm spacer was successfully delivered to the patient for an in-field right neck nodal recurrence. He received a total EQD2/BED dose of 127.70/153.24 Gy. At 1-year followup, the patient was without evidence of recurrent disease or new significant side effects. Conclusion: Recurrent head and neck cancer should be managed with a multidisciplinary approach given the complex clinical scenario. Reirradiation is a commonly used salvage measure for recurrent head and neck cancer that requires careful planning and patient selection due to prior treatment-related effects and dose constraints. We reported a case of a second course of reirradiation using interstitial HDR-brachytherapy for locoregionally recurrent head and neck cancer and showed no recurrence of disease or worsening long term side effects at 1 year.
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Purpose: Despite the promising palliative effects of radiation treatment, few reports have studied the role of palliative tumor surgery (PTS) in patients with unresectable head and neck cancer (HNC). Thus, we aimed to present the outcomes of PTS in HNC, and suggest a possible surgical indication for PTS.Methods: We retrospectively reviewed the medical records of 18 patients who underwent PTS for HNC between 2002 and 2017. PTS was defined as surgical debulking of tumor or surgery of loco-regionaltumors in patients with distant metastasis. As functional outcomes, we evaluated changes in pain, diet, respiration, and wound care before and after PTS.Results: Squamous cell carcinoma was the common cancer type (72.2%), followed by salivary gland cancers and others. The median overall survival time was 17 months (95% confidence interval, 7.3 to 26.7). PTS significantly reduced the pain score (P= 0.013), and improved cancer-related wounds (P=0.003 in wound infection). Oral swallowing and respiration status did not change after PTS. The recurrenttumor atthe operation bed was clinically detected at post-operative 1 to 2 months with intact skin (without wound problems). Of note, further chemotherapy or other additional cancer treatments was possible in 66.7% of patients with PTS (P=0.002).Conclusion: PTS could provide a meaningful benefitto selected patients with incurable HNC, in terms of pain control and cancer wound management. Thus, PTS is a considerable option for selected HNC patients, based on the accurate evaluation oftumor extent along with multi-disciplinary consultation as well as patient counseling.
Article
Aim: In India, more than 70% patients present as locally advanced head-and-neck cancers (LAHNC), with poor performance status and are suitable candidates for palliative radiotherapy (RT) aimed at symptom relief. This prospective study aims to compare two different short course hypo-fractionated RT regimens in patients of LAHNC at a regional cancer centre of north-west India. Materials and methods: A total of 70 patients of LAHNC were randomized to receive palliative RT in two groups of 35 each. Group A received 30 Gy/10# over 2 weeks and Group B received 20 Gy/5# over 1 week. Baseline symptoms of pain, dysphagia, insomnia, dysphonia, bleeding, fungation, and dyspnea were assessed before the start of study. The first assessment for toxicities, subjective and objective response was done at the conclusion of RT and then after 4-6 weeks. Results: Out of total 70 patients, 71% were males and 29% were females with a median age of 54 years. The most common sites were oropharynx (39%) followed by larynx (24%), oral cavity (20%), and hypopharynx (17%). Nearly 60% of the patients in both groups presented in stage IV and 40% in stage III. At conclusion of RT and at 4-6 weeks follow-up, both groups showed similar results in terms of symptom palliation, objective response, and acute toxicities. Group B showed higher incidence of Grade III and above mucositis (P = 0.027). Median overall survival was found to be 5.9 months (range 1-15 months) in group A and 6.1 months (range 1-18 months) in Group B. Conclusion: Hypo-fractionated RT promises to effectively relieve symptoms in LAHNC and reduces the need of analgesics and hospital visits. Furthermore, a shorter overall treatment time is beneficial at high volume centers and is also welcomed by patients with shorter life expectancy.
Article
Objectives Palliative radiotherapy regimens for advanced head and neck cancers vary in doses and treatment times. Their quality of life (QoL) implications are not clearly established. Methods We randomised patients with advanced, non-metastatic, head and neck squamous cell carcinomas (stage IVA-B) with WHO performance score of 2 or higher to receive 30 Gy in 10 fractions over two weeks (arm A) or 20 Gy in 5 fractions over one week (arm B). QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-H&N35 questionnaires at baseline and postradiotherapy. The primary endpoint was the EORTC-defined global health status. Secondary endpoints were functional and symptom scores of QoL, response to radiotherapy and acute toxicities. The primary aim was to evaluate the one-week regimen in terms of QoL to the longer regimen. Results 110 patients were randomised, the number of patients in the final analysis was 95: 49 in arm A and 46 in arm B. Baseline characteristics were similar. Clinical outcomes post-treatment were comparable. Postradiotherapy, there were improved scores for functional and symptom scales, the differences were non-significant. The duration of treatment was significantly reduced in arm B (p<0.01) with a lower score for financial difficulty (p<0.001). The difference in global health status (primary endpoint) was non-significant (p=0.82). The median overall survival was 7 months, the median progression-free survival was 5 months and these did not vary between the two groups. Conclusion One-week palliative radiotherapy for head and neck cancers achieves similar QoL and clinical outcomes as more protracted radiotherapy schedules with significantly reduced treatment time and financial toxicity.
Article
Introduction: Squamous cell cancer of the head and neck (HNSCC) represents the sixth most common malignancy, with 6,50,000 new cases and 3,00,000 HNSCC related deaths reported annually worldwide. HNSCC constitutes approximately 90 percent of all head and neck cancers, and accounted for approximately 3 percent (about 50,000) of all new cancer cases and 2 percent (approximately 12,000) of all cancer deaths in 2010 in the United States. Overall, 57.5% of global head and neck cancers occur in Asia. Aims And Objectives: To Determine Local Control And Quality Of Life in stage III & IV Advanced HNSCC Following Hypo Fractionated Palliative Radiotherapy. To study the response with hypo fractionated external beam radio therapy treatment using RECISTcriteria (version 1.1). Materials And Methods: At the completion of treatment both the primary and the node Response was assessed as per the RECIST 1.1 Response Criteria and Quality of life with QLQ H&N 35 module. Results And Conclusion: At the completion of RT, 32.1% had CR, 50% had PR,14.3% had SD and 3.6% had PD. At 4 weeks of follow-up, 28.6% had CR, 53.6% had PR,14.3% had SD and 3.6% had PD. At 3 months of follow up 17.9% had CR, 60.7% had PR,10.7% had SD and 10.7% had PD. There is a statistically signicant improvement in distressing symptoms like pain, swallowing difculty, opening mouth difculty. This fractionation schedule allowed treatment to be completed in a short overall period with good tolerance and clinically acceptable toxicities
Article
Locally advanced Head and neck squamous cell carcinoma (SCCHN) represents a common oncologic pathology in older adults (OA). While radiotherapy represents a cornerstone in this context, it is unclear what is the optimal radiation regimen for SCCHN in the palliative setting, especially for OA. This article addresses issues related to palliative radiotherapy (PRT) in this setting with a focus on treatment modalities and toxicity. We also explore the use of quality of life and geriatric assessment in this setting. Medline, Scopus and Embase databases were queried for articles in this setting. We included studies published from January 1, 2000 through June 1, 2020, that were independently evaluated by two authors. Analyzed endpoints were progression free survival (PFS), overall survival (OS) and PRT toxicities. The meta-analysis was performed using Stata v.14. A total of 33 studies were included in this meta-analysis. The pooled median OS is 7.7 months, 2-years OS was worse for higher radiation dose (p = 0.02). The pooled median PFS was 5.4 months, PFS was influenced by EQD2 (p = 0.01), with patients receiving an EQD2 < 40 Gy that presented a poorer outcome. Regarding acute toxicities, most common pooled G3 toxicities were mucositis (7%) and dysphagia (15%). Among late toxicity, most common G3 toxicity was dysphagia in 7% of patients. Radiotherapy should be the most effective palliative treatment in symptomatic SCCHN OA. A tailored approach, guided by geriatric tools, would be indicated to choose the right therapy.
Article
Purpose To identify predictors of palliation for head and neck cancer treated with the “Hypo Trial” hypofractionated radiation therapy regimen in a clinical setting. Design/Method We retrospectively assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30‐36Gy in 5‐6 biweekly fractions of 6Gy. Results The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow‐up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression‐free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01). Conclusions This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.
Article
Purpose To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts). Patients and methods Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2–4 weeks, without any systemic therapy. Results Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7–98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1–58.3). Local control at 12 and 24 months was 72.8% IC95%[62–85.5] and 51.7% IC95%[38.1–70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4–60.8] and 41% IC95%[15–36.4] respectively, with a median of 11.5 months IC95%[8.9–17]. OS at 12 and 24 months were 60.4% IC95%[50–73.1] and 41% IC95%[30.6–54.9] respectively, with a median of 19.3 months IC95%[11.9–25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts. Conclusion The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT.
Article
Background: Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes. Aims and objectives: To assess the outcomes of hypofractionated "Christie" palliative radiotherapy regimen in advanced HNSCC. Materials and methods: Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria. Results: Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 - 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 - 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization. Conclusion: Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting.
Article
Objectives To assess the feasibility and safety of a repeated SHort course Accelerated RadiatiON therapy (SHARON) regimen in the palliative setting of Head and Neck (H&N) cancer in older adults. Material and Methods Patients with histological confirmed H&N cancers, age ≥ 80 years, expected survival >3 months, and Eastern Cooperative Oncology Group (ECOG) performance status of ≤3 were enrolled. Patients were treated in cohorts of six patients: a total dose of 20 Gy was delivered in 2 consecutive days with a twice-daily fractionation (5 Gy per fraction) and at least 8-h interval. If no Grade 3 toxicity was registered, a second enrollment started with another cohort of six patients to whom were administered two cycles (total dose of 40 Gy). The primary endpoint was to evaluate the feasibility of the two cycles of treatment. Secondary endpoints were evaluation of symptoms control rate, symptoms-free survival (SFS), and Quality of Life (QoL) scores. Results Seventeen consecutive patients (median age: 85 years) were treated. Nine patients were treated with one cycle and 8 patients with two cycles. No G3 toxicity was reported in either cohort. With a median follow-up time of 4 months, 3-month SFS in the first and second cohorts was 83.3%, and 87.5%, respectively. The overall palliative response rate was 88%. Among 13 patients reporting pain, 8 (61.5%) showed an improvement or resolution of their pain. Conclusion Repeated short course accelerated radiotherapy in a palliative setting of H&N cancers is safe and well-tolerated in older adults.
Article
Objectives (1) To estimate the association between neck dissection lymph node yield (LNY) and survival among patients with surgically treated human papilloma virus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC). (2) To identify a clinically relevant quality metric for surgical treatment of HPV-related OPSCC. Study Design Retrospective cohort study. Setting National Cancer Database. Subjects and Methods From the National Cancer Database, 4130 patients were identified with HPV-associated OPSCC treated with primary surgery from 2010 to 2016. Based on prior literature, an adequate neck dissection LNY was defined as ≥18 lymph nodes. To determine whether LNY is associated with survival, univariable and multivariable Cox proportional hazards regression was performed. Analysis was stratified by adjuvant therapy regimen. Results A total of 2113 patients (51.2%) underwent surgery with or without adjuvant radiation (S ± RT), and 2017 patients (48.8%) underwent surgery with adjuvant chemoradiation. LNY ≥18 was associated with a 5-year survival benefit of 7.15% (91.7% for LNY ≥18, 84.5% for LNY <18, P = .004) for the S ± RT cohort on unadjusted survival analysis. For the S ± RT group, LNY ≥18 was associated with decreased hazard of death (hazard ratio, 0.45; 95% CI, 0.29-0.70; P < .001) after adjustment for patient characteristics, TNM staging, surgical margins, extranodal extension, and treating facility characteristics. For surgery with adjuvant chemoradiation, the adjusted hazard ratio estimate for LNY ≥18 was 0.64 (95% CI, 0.41-1.00), but the result was not statistically significant ( P = .052). Conclusion An adequate LNY from a neck dissection may affect survival when HPV-related OPSCC is treated with up-front surgery.
Article
Background Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity. Methods A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35‐40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions. Results Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity. Conclusion SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL.
Article
A 74-year-old man presented with recurrent syncope 3 months after definitive surgery for hypopharyngeal cancer. The patient experienced dizziness and severe hypotension on the movement of the neck and head. CT revealed disease recurrence with masses encasing the left internal carotid artery. The patient was diagnosed with vasodepressor type of tumour-induced carotid sinus syndrome (tiCSS) and was referred for palliative intensity-modulated radiotherapy (IMRT). Ten days after the commencement of IMRT (25 Gy in five fractions), the symptoms of tiCSS improved, and there was no re-exacerbation of the symptoms till the patient died 56 days after the commencement of RT. Palliative IMRT was feasible and effective for recurrent malignant tiCSS. Given the fact that palliative IMRT is minimally invasive, this option could be widely adapted for patients with such poor general condition and prognosis.
Article
Background No randomized controlled trials (RCT) have yet identified the optimal palliative radiotherapy scheme in patients with incurable head and neck squamous cell carcinoma (HNSCC). We conducted RCT to compare two radiation schemes in terms of efficacy, toxicity and quality-of-life (QoL). Materials and methods Patients with locally-advanced HNSCC who were ineligible for radical treatment and those with limited metastatic disease were randomly assigned in 1:1 ratio to arm 1 (36 Gy in 6 fractions, twice a week) or arm 2 (50 Gy in 16 fractions, four times a week). Results The trial was discontinued early because of slow accrual (34 patients enrolled). Objective response rates were 38.9% and 57.1% for arm 1 and 2 respectively (p=0.476). The median time to loco-regional progression was not reached. The loco-regional control rates at 1 year was 57.4% and 69.3% in arm 1 and 2 (p=0.450, HR=0.56, 95%CI 0.12-2.58). One-year overall survival was 33.3% and 57.1%, with medians of 35.4 and 59.5 weeks, respectively (p=0.215, HR=0.55, 95%CI 0.21-1.43). Acute grade ≥3 toxicity was lower in arm 1 (16.7% versus 57.1%, p=0.027), with the largest difference in grade 3 mucositis (5.6% versus 42.9%, p=0.027). However, no significant deterioration in any of the patient-reported QoL-scales was found. Conclusion No solid conclusion could be made on this incomplete study which is closed early. Long-course radiotherapy did not show significantly better oncologic outcomes, but was associated with more acute grade 3 mucositis. No meaningful differences in QoL-scores were found. Therefore, the shorter schedule might be carefully advocated. However, this recommendation should be interpreted with great caution because of the inadequate statistical power.
Article
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The treatment of metastatic head and neck squamous cell carcinoma (HNSCC) with a combination of radiotherapy (RT) and immunotherapy can augment treatment response and symptomatic relief. Combination therapy can also trigger a non-targeted tumor control event called the abscopal effect. This effect can be demonstrated by treatment with anti- programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti- cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies in combination with hypofractionated RT. Individual studies and clinical trials have revealed that combination radio-immunotherapy improves overall treatment response by successful initiation of the abscopal effect, which extends the treatment effects to non-targeted lesions. Growing attention to the abscopal effect may inspire innovations in current radiotherapy toward more effective and less toxic radiobiological treatment modalities for advanced HNSCC. We review the latest findings on the abscopal effect with emphases on therapeutic modalities and potential applications for treating metastatic HNSCC.
Article
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Background: Incurable inflammatory breast cancer (IBC) patients occasionally suffer from general symptoms such as breast pain, bleeding, ulceration, and discharge, and thus require palliative radiotherapy (RT). Hypofractionated RT has many advantages in palliative settings, but very few studies on IBC have been conducted. This study was conducted to evaluate the effects of hypofractionated RT on symptomatic IBC patients. Methods: Twenty-two patients with IBC who underwent hypofractionated palliative RT between 2010 and 2016 were retrospectively analyzed. RT was performed at a total dose of 42.5-55 Gy with 2.5-3 Gy per fraction. The treatment effects were evaluated with respect to symptom improvement, tumor response, and treatment-related toxicity. Results: The main symptoms that the patients complained of before RT were pain, bleeding, and discharge. According to the percentage of symptom relief compared with pre-RT symptoms, the number of patients with < 30, 30-70%, and ≥ 70% were 2 (9.1%), 7 (31.8%), and 13 (59.1%), respectively. Eighteen (81.8%) patients showed tumor response. No patient experienced grade 3 or higher acute or chronic toxicity during a median follow-up period of 13 months. In univariate analysis, symptom type was a significant factor for predicting the degree of symptom relief. Meanwhile, RT field and C-reactive protein increase were significant factors for predicting the incidence of radiation-induced skin toxicity. Conclusions: Hypofractionated RT could safely and effectively relieve symptoms among incurable symptomatic IBC patients.
Article
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In metastatic or locally advanced head and neck tumors that present in frail patients or after chemotherapy progression, radiotherapy is normally used as a palliative treatment, with a high rate of symptom palliation and improvement in quality of life. However, there is controversy about what the optimal regimen is. Moreover, despite the poor prognosis of metastatic head and neck cancer, different retrospective studies have shown that a minority of patients with oligometastatic disease experience prolonged disease-free survival after adding curative radiotherapy treatment to the metastatic disease and/or primary tumor. Different retrospective studies have identified clinical prognostic factors that may be used to select candidate patients with metastatic head and neck cancer for a radical approach with radiotherapy. The purpose of this manuscript is to review the role of radiotherapy in metastatic and locally advanced head and neck tumors.
Article
Background: Large number of patients with head-and-neck cancer presents with factors such as advanced disease, poor general condition, and associated comorbidities due to which radical treatment is not recommended in these patients. In this scenario, the aim of the present study is to assess the role and feasibility of hypofractionated palliative radiotherapy in these patients. Subjects and Methods: This study was conducted on patients with histopathologically proven cases of squamous cell carcinoma of the head-and-neck region who were surgically unresectable. The quality of life (QOL) was assessed before and after 1 month of radiotherapy using University of Washington Quality of Life questionnaire version 4. All patients received 40 Gy in 10 fractions, twice weekly by two lateral fields covering primary and secondary disease. Response evaluation criteria in solid tumor criteria were used to assess the tumor response. Toxicity was assessed weekly using radiation therapy oncology group criteria. Results: A total of 50 patients were enrolled in this study, out of which 46 completed the planned treatment of 40 Gy in 10 fractions. Common complaints were distressing pain at the primary site (42%), neck swelling (30%), difficult in swallowing (18%), and change in voice (10%). Statistically significant improvements were observed in overall QOL (26.9 ± 9.63 to 55.65 ± 19.28) and none of them experienced Grade IV mucositis or skin toxicity. Good objective response was seen in 82.6% and 84.7% of patients at primary and nodal sites, respectively. Conclusions: This hypofractionated palliative radiotherapy regimen is a good treatment option in patients with Stage IV head-and-neck cancer, who are not fit for treatment with curative intent.
Article
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This is a study of 5595 head and neck cancer patients treated during 1987-89 at TMH, Mumbai. The study included 1970 oral cancers (ICD 140-145), 1495 oropharyngeal cancers (ICD 1410, 1453, 146), 1255 hypopharyngeal cancers (ICD 148), 125 nasopharyngeal cancers (ICD 147) and 750 laryngeal cancers (ICD 161). The clinical extent of disease at presentation was based on TNM group staging (UICC 1978). For the majority of sites, patients attended the hospital during stage III and stage IV of the disease; the only exception was for cancers of the lower lip, anterior tongue and vocal cord when between 46.2% and 56.5% of patients with localized cancer (stage I and II) were seen. Generally, surgery either alone or with radiation has been administered for oral cancer patients whereas radiation either alone or in combination with chemotherapy was administered for other head and neck sites. The overall 5-year survival rate was in the range of 20-43% for oral cancer, 8-25% for pharyngeal cancers and 25-62% for laryngeal cancer. The 5-year relative survival rates were more or less in agreement with the results published by the Eurocare study for head and neck cancers. The importance of primary prevention in head and neck cancer is stressed.
Article
Backgroundand purpose: Radiation therapy is often the primary treatment for advanced cases of head and neck cancers not considered suitable for radical surgery. In these cases locoregional tumour control rates are low and has warranted innovative treatment modifications, such as altered fractionation schedules and combination with chemotherapy.Patients and methods: From October 1990 to December 1997, 239 patients with squamous cell cancers originating in the head and neck region were randomized to one of three treatment options. Standard therapy consisting of conventional fractionation with 70 Gy in 7 weeks in 35 fractions (CF). The second treatment option consisted of a continuous hyperfractionated accelerated radiotherapy delivering a total dose of 55.3 Gy in 33 fractions over 17 consecutive days (V-CHART). The third study arm had identical fractionation and dose as the above accelerated treatment, with the additional administration of 20 mg/m2 mitomycin C (MMC) on day 5 of treatment (V-CHART+MMC).Results: Main toxicity resulted from accelerated fractionation in confluent mucositis (Grade 3–4 in 95%) requiring nasogastral tube feeding, analgetics and antiphlogistics in the majority of cases. Haematological toxicity Grade 3–4 was seen after MMC administration in 18%. MMC administration did not influence mucosal reaction. Overall duration of mucositis was not different in the three treatment groups. Loco-regional tumour control was 31% after CF, 32% after V-CHART and 48% after V-CHART+MMC, respectively (P
Article
Squamous cell carcinoma of head and neck (SCCHN) is one of the commonest cancers seen in India, constituting up to 25% of their overall cancer burden. Advanced SCCHN is a bad disease with a poor prognosis and patients usually die of uncontrolled loco-regional disease. Curative intent management of loco-regionally advanced SCCHN has become more evidence-based with active clinical research in the form of large prospective randomized controlled trials and meta-analyses. However, little has been written about palliative radiotherapy (PRT) in head and neck cancers. It is widely recognized that PRT provides effective palliation and improved quality-of-life in advanced incurable malignancies. It is in this context that this study proposes to review the existing literature on palliative radiotherapy in advanced incurable SCCHN to help formulate consensus guidelines and recommendations.
Article
A random controlled trial was performed to compare long and short fractionation of radiotherapy in patients with head and neck cancer with a poor prognosis. Ninety-eight matched pairs were treated, one member of each pair received 10 fractions in 22 days, the other 30 fractions in 42 days. The same nominal standard dosages were used in each arm of the trial. Mucosal reactions were more severe with 10 fractions, skin reactions more severe with 30 fractions. No difference in survival, local tumour control rates or late normal tissue effects could be demonstrated. It is suggested that any possible therapeutic advantage of prolonged fractionation is minimal and that it is justified to use a small number of large fractions in clinical trials involving hyperbaric oxygen or electron-affinic sensitizers.
Article
The irradiation of locally advanced, inoperable, squamous cell caricinomas of the head and neck with conventional fractionation schedules using 200 rads/day has produced poor results. A prospectively randomized, clinical trial has been started comparing conventional with large daily fractions of 400 rads/day for 10-12 treatments. Results suggest that improved tumor control and survival rates might be obtained with the use of large daily fractions.
Article
Most experienced head and neck surgeons recommend aggressive treatment--including radical surgery--for patients with resectable Stage IV cancers. Yet, given the poor overall cure rate of 15% and the deformity and disability often associated with treatment, one of the most frequently asked questions at our conference on tumors was: Are we really helping these patients? We found little data in the relevant literature to answer this or other questions. Are there subgroups with a better outlook? What is the evidence for palliation in the 85% of patients who fail treatment and how is it best achieved? How do patients and their families view their treatment in retrospect? To find the answers, we studied the records of 76 consecutive patients (previously untreated) who presented with Stage IV carcinoma of the upper aerodigestive tract in 1981-82. We also interviewed surviving patients or family members and friends by phone. Overall mean survival was 15 months, with a 2-year disease-free survival rate of 16%. More to the point, resectable patients treated with curative intent had a mean survival of 19.4 months, and 12 of 42 patients (29%) were disease-free at 2 years. Patients with laryngeal cancer had the best survival results, and patients with sinus cancers had the worst (25.2 vs. 10.5 months). Those with N2A staging lived longer than other groups (24.1 vs. 12.1 months). T4 lesions portend a particularly poor prognosis; mean survival was just 7.5 months and only 1 of 28 patients (3.6%) was alive and disease-free at 2 years. Twenty-five percent of patients returned to normal function, but 75% had significant problems eating or speaking.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
• Short-course, high fractional dose radiation therapy was compared with the conventional protracted radiation schedule in the treatment of advanced (stages III and IV) head and neck cancer. Sixty-four patients with surgically unresectable squamous cell carcinoma were randomized to receive either 6,000 to 7,000 rad in six to seven weeks or 4,000 to 4,800 rad in two to three weeks. The palliative benefits of irradiation were comparable in the two treatment arms, and complete tumor regression was observed in the majority of patients in both groups. There was no difference between the groups with regard to either short-term normal tissue radiation reaction or long-term complications. High fractional dose irradiation appears to yield results equivalent to those of conventionally fractionated radiation therapy in advanced head and neck cancer and deserves further study both as primary treatment and in combination with surgery. (Arch Otolaryngol 1983;109:98-102)
Article
To establish the feasibility of performing split-course accelerated hyperfractionation (AHFX-S) and concomitant boost accelerated fractionation radiotherapy (AFX-C) for advanced head and neck cancer in a multi-institutional cooperative trial setting and to evaluate the tumor clearance rate and acute and late toxicity of these fractionation schedules. Between February 1989 and January 1990, 75 patients with Stage III or IV squamous cell carcinoma of the head and neck were randomized to receive: (a) AHFX-S: 1.6 Gy/fraction, twice daily (6-h interval), 5 days/week, to a total dose of 67.2 Gy/42 fractions/6 weeks, with a 2-week rest after 38.4 Gy; or (b) AFX-C: 1.8 Gy/fraction/day, 5 daily fractions/week to 54 Gy/30 fractions/6 weeks to a large field and 1.5 Gy/fraction/day to a boost field, 6 h after large field treatment during the last 11 treatment days, to a total dose of 70.5 Gy/41 fractions/6 weeks. Acute and late toxicities were scored according to the RTOG normal tissue reaction scales and tumor clearance was evaluated at completion of therapy and at regular intervals thereafter. Of the 70 analyzable patients, 38 received AHFX-S and 32 received AFX-C. The two arms were balanced with respect to sex, age, T-stage, and Karnofsky Performance Status (KPS). However, the AHFX-S arm had a higher proportion of oropharyngeal primaries (63% vs. 44%), and Stage IV disease (82% vs. 50%) and lower proportion of oral cavity lesions (3% vs. 22%) and N0 disease (16% vs. 31%) than the AFX-C arm. The median follow-up was 2 years (range: 0.03-4.87 years). Tolerance of both variants of accelerated fractionated radiotherapy was satisfactory. There was no significant difference in local-regional control, disease-free survival, or survival between the two arms. The 2-year local-regional failure rate, survival, and disease-free survival was 50, 50, and 40%, respectively, for the entire group of patients. Acute radiation mucositis was increased in both arms. There was no significant difference in the incidence of grade 3 acute toxicities (63% vs. 56%) and grade 3 (14% vs. 14%) or grade 4 (6% vs. 17%) late toxicities. Permanent grade 4 late toxicity was observed in 6 and 7% of the patients, respectively. Results of this randomized Phase I/II trial showed that the two accelerated fractionated schedules studied can be successfully given in a multi-institutional cooperative trial. There was no significant difference in acute or late toxicities, local-regional control, disease-free survival, or survival in this small scale study. Therefore, a Phase III trial comparing the relative efficacy of these two accelerated fractionation schedules against standard fractionation and hyperfractionation has been activated.
Article
The role of radiotherapy in the palliation of patients with advanced cancer of the head and neck is not clear. Several distinctive characteristics of advanced head and neck cancer contribute to the complexities in the choice of appropriate palliative management strategies. Palliative treatment may be the appropriate management for a proportion of patients with advanced disease, but the current stage groupings of head and neck cancer are not sufficient for use in the reliable identification of such a patient group. Controversy arises because of the difficulties in distinguishing patients who should be offered conventional treatment with curative intent from those appropriate for treatment with palliative intent. A structured review of the cancer and quality of life literature identified 298 references pertaining to palliative radiotherapy in head and neck cancer, 26 of which met the criteria for inclusion in this review. An expert panel discussed the literature, and concluded that insufficient information precluded estimations of the frequency, degree of, or duration of symptomatic relief that radiation offered to those patients not cured of their disease. Moreover, the currently available literature does not address the toxicity or appropriate dose and fractionation of palliative radiotherapy in this setting. Further studies are necessary to evaluate clinical endpoints appropriate to the use of radiotherapy in the palliative management of patients with advanced head and neck cancer. Studies are also needed to refine the current clinical classification of patients, allowing the identification of patients suitable for palliative management.
Article
Palliative care is the active total care of patients whose disease is not responsive to curative treatment. Patients with end-stage head and neck cancer have particular problems because of the impact of the tumour on the airway, the upper gastrointestinal tract and the major senses. Patients referred for palliative care were identified from the hospice database and the nature, incidence and management of their problems, and the role of the hospice in their care, was reviewed from in-patient and home care notes and patient-generated problem lists. Thirty-two male and six female patients with a median age of 64 years were identified. Locoregional recurrence was present in 79% of patients. Pain, weight loss, feeding difficulties, dysphagia, respiratory symptoms, xerostomia, oral thrush and communication difficulties were the major problems. The management of each, and of the terminal events encountered in the group, is discussed.
Article
The choice of palliative treatment and the prognostic factors in unresectable head and neck cancer cases continue to be controversial. In the present study we compared the survival rates of untreated stage IV head and neck cancer patients with cases managed prospectively at A.C. Camargo Hospital for Cancer with neoadjuvant chemotherapy, concomitant chemotherapy or radiotherapy alone. Previous results had shown that while the type of treatment did not influence survival rates (P = 0.706), tumor response to treatment (whether complete, partial or none) significantly influenced survival (P = 0.00002). In the present study we compared the survival rates in the groups with untreated patients (who remained untreated until death) with the same demographic and clinical characteristics of patients receiving treatment. We found that there was a significant difference between the survival rates of the untreated group and those of the treated groups that was independent of the type of treatment performed (P < 0.00001) or the tumor response to treatment (P < 0.0001).
Article
This paper describes the characteristics and natural history of the largest reported group of patients with untreated head and neck cancer. From 1953 to 1990, 808 untreated head and neck cancer patients were followed-up until their death. All patients were given supportive care, but specific oncological treatment was not pursued secondary to advanced tumour stage, poor performance status and/or patients' refusal of any treatment. The overall survival ranged from 1 day to 53.8 months (median 3.82 months). Performance status was the most significant predictor of survival (P < 0.001). A subgroup of 357 patients with good performance status and aged less than 70 years old had a 12.9% 1-year survival. Approximately 50% of untreated head and neck cancer patients will die within 4 months of their diagnosis. However, the remaining patients can survive up to 4 or more years, depending on their tumour location, extent, performance status and level of supportive care.
Article
Between 1994 and 1997, 22 patients with dysphagia from advanced incurable esophageal cancer were enrolled in a phase I/II prospective study to assess the palliative benefit and toxicity of a short course of radiotherapy with chemotherapy. The study population included 17 men and five women with a median age of 69 (range 43-84). Patients were treated with 30 Gy in ten fractions to the mediastinum with a concurrent single course of chemotherapy (5-FU, 1000 mg/m(2), days 1-4 and mitomycin-C 10 mg/m(2), day 1). Swallowing ability was recorded each day on a self-administered diary card using the five point dysphagia index of the MRC (UK). The median baseline MRC swallowing score was 4 (cannot swallow solids). Treatment was generally well tolerated, but seven (32%) patients had transient worsening of dysphagia scores immediately following treatment because of esophagitis; fifteen (68%) achieved a complete response (score 1: no difficulty on swallowing) with a median time to normalization of swallowing of 5 weeks. For these patients, the median dysphagia-free interval from time of onset of improvement was 11 weeks (range 1-131 weeks) and 11 (73%) remained dysphagia-free until death. The remaining patients had no or marginal improvement. Univariate analysis showed no difference between responders and non-responders with respect to age, gender, or histology. Median survival for the entire study population was 20 weeks (range 3-135 weeks). This prospective trial shows that a short course of radiotherapy plus chemotherapy may produce complete relief of swallowing difficulties in a substantial proportion of patients with acceptable toxicity.
Article
Radiation therapy is often the primary treatment for advanced cases of head and neck cancers not considered suitable for radical surgery. In these cases locoregional tumour control rates are low and has warranted innovative treatment modifications, such as altered fractionation schedules and combination with chemotherapy. From October 1990 to December 1997, 239 patients with squamous cell cancers originating in the head and neck region were randomized to one of three treatment options. Standard therapy consisting of conventional fractionation with 70 Gy in 7 weeks in 35 fractions (CF). The second treatment option consisted of a continuous hyperfractionated accelerated radiotherapy delivering a total dose of 55.3 Gy in 33 fractions over 17 consecutive days (V-CHART). The third study arm had identical fractionation and dose as the above accelerated treatment, with the additional administration of 20 mg/m(2) mitomycin C (MMC) on day 5 of treatment (V-CHART+MMC). Main toxicity resulted from accelerated fractionation in confluent mucositis (Grade 3-4 in 95%) requiring nasogastral tube feeding, analgetics and antiphlogistics in the majority of cases. Haematological toxicity Grade 3-4 was seen after MMC administration in 18%. MMC administration did not influence mucosal reaction. Overall duration of mucositis was not different in the three treatment groups. Loco-regional tumour control was 31% after CF, 32% after V-CHART and 48% after V-CHART+MMC, respectively (P<0.05). Overall crude survival was 24% after CF, 31% following V-CHART and 41% after V-CHART+MMC, respectively (P<0.05). Median follow up was 48 months (assessment performed in February 1999). Following shortening overall treatment time from 7 weeks to 17 consecutive days and dose of radiotherapy from 70 to 55.3 Gy the results in the radiotherapy only treated patients are identical. A significant improvement regarding local tumour control and survival was seen following administration of MMC to the accelerated fractionated treatment.
Article
Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT.
Article
To reach a consensus on a set of optimal endpoint measurements for future external beam radiotherapy trials in bone metastases. An International Bone Metastases Consensus Working Party invited principal investigators and individuals with a recognized interest in bone metastases to participate in the two surveys and a panel meeting on their preference of choice of optimal endpoints. Consensus has been reached on the following: (a) eligibility criteria for future trials; (b) pain and analgesic assessments; (c) radiation techniques; (d) follow-up and timing of assessments; (e) parameters at follow-up; (f) endpoints; (g) re-irradiation; and (h) statistical analysis. Based on the available literature and the clinical experience of the working party members, an acceptable set of endpoints has been agreed upon for future clinical trials to promote consistency in reporting. It is intended that the consensus will be re-examined every 5 years. Areas of further research were identified.
Article
Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC. Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms. The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01). The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.
Article
A proportion of advanced stage head and neck cancer patients are incurable and have a limited life expectancy of 100 days or less. The study aimed to offer a short course of palliative radiotherapy (PRT) and evaluate the symptom relief, disease response and duration of survival. Between 1995 and 2001, 505 patients of stage IV squamous cell carcinoma received uniform dose of 20 Gy in 5 fractions over 1 week along with symptom relief drugs. Incurable status and decision for palliation was made conjointly. Distressing symptoms were assessed before PRT. Patients showing more than 50% objective regression (PR) at tumor and nodal sites received further RT (FRT) up to 70 Gy. The overall PR rate was 37% (189 patients), but 153 (30%) completed FRT, and rest 352 were followed up after PRT only. None of the patients died due to radiation toxicity, and the radiation morbidities were confined to dry desquamation and patchy mucositis, which healed over 1 month. Symptom relief for pain, dysphagia, hoarseness, cough and otalgia was obtained in 47%-59% of the patients following PRT. The overall survival ranged from 34 days to 2065 days and median survival to PRT and FRT were 200 days and 400 days, respectively. Only 10% were disease-free after FRT. Unfavourable advanced stage head and neck cancer can be identified for a suitable short course of palliative radiotherapy which will achieve growth restraint and symptom relief in sizeable proportions for an approximate period of 7 months.
Article
The primary objective of this study was to estimate the rate of tumour response to a cyclical hypofractionated palliative radiotherapy regimen (QUAD SHOT) in previously untreated patients with incurable squamous cell carcinoma of the head and neck. Secondary objectives were to prospectively evaluate toxicity, quality of life (QoL) and survival in these patients. The QUAD SHOT consisted of 14 Gy in four fractions, given twice a day and at least 6h apart, for 2 consecutive days. This regimen was repeated at 4 weekly intervals for a further two courses if there was no tumour progression. The QoL tool used was an abbreviation of the EORTC QLQ-C30. Thirty eligible patients (29 Stage IV, 20 performance status 2-3) had at least one treatment and 16 patients completed all three cycles. Sixteen patients (53%) had an objective response (2CR, 14PR) and a further seven had stable disease. Median overall survival was 5.7 months, median progression free survival was 3.1 months. The treatment was very well tolerated, with improved QoL in 11 of 25 evaluable patients (44%). The QUAD SHOT regimen is an effective palliative treatment with minimal toxicity and a good response rate, which impacts positively on patients' QoL.
Article
We aimed to examine deficiencies in established methods of summarising adverse events, and to create a new reporting system (TAME) for summarising the toxicity burden of cancer treatment. TAME consolidates traditional adverse-event data into three risk domains: short-term (acute) Toxicity (T), Adverse long-term (late) effects (A), and Mortality risk (M) generated by a treatment programme (E=End results); and assigns treatments to risk classes for each risk domain. We examined formally an established method for summarising adverse events (the max-grade method) in five trials of patients with head and neck cancer done between September, 1991, and August, 2000, by the Radiation Therapy Oncology Group (RTOG) that involved 13 treatment groups (2304 patients). We calculated TAME summary metrics that included time and multiplicity factors in the same patient groups. We compared relative T values with relative values for toxic effects from the max-grade approach. We also calculated the range of individual patient T scores in two groups from one of the trials (the laryngeal-preservation trial). The max-grade method systematically excluded 29-70% of total reported high-grade (grade 3-4) acute adverse events, contained progressive bias, and favoured higher toxicity programmes. Relative T values in the 13 treatment programmes tested showed an increase of almost 500% in acute toxicity burden (100-590) between treatment groups compared with a 170% increase (100-270) between treatment groups by use of the max-grade method. The difference between these two summary systems was statistically significant (mean difference -102 [95% CI -167 to -37], p=0.005, t test for paired differences). Four risk classes were designated for acute and relative late effects: low (100-140), moderate (150-390), high (400-490), and extreme (>or=500). The distribution of individual patient T scores showed that 82 (60%) patients who received concurrent platinum-radiotherapy for larynx preservation reported two or more high-grade events, and 34 (20%) reported four or more high-grade events; these findings differed significantly from the distribution of individual patient T scores for patients who received radiotherapy alone, in which 32 (19%) reported two or more high-grade events and 3 (3%) reported four or more high-grade events (p<0.0001). The max-grade method also systematically excluded 26-48% of high-grade (grade 3-4) late adverse events. However, less variation was noted in the relative risk of late events (100-270) by the TAME method for late effects. Traditional methods for summarising adverse events systematically exclude important data, giving an inaccurate impression of the toxicity burden in complex multimodality trials. By contrast, T values use data on all high-grade adverse events. T values are proportional to the intensity of treatment, showing a 500% increase between treatment groups in acute toxicity burden in RTOG trials of head and neck cancer done during this study interval. TAME reporting provides a concise and uniform method to compare relative risk among treatment options. Future studies should include testing the performance of the TAME system in additional datasets (from different research organisations and disease sites), prospective correlation of TAME endpoints with predefined outcome measures, and assessment of its usefulness in clinical decision making.
Article
The primary purpose of the trial was to assess rate of tumour response to a hypofractionated course of radiotherapy in patients with incurable squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives included radiation toxicity, symptom control, quality of life (QoL) and progression-free and overall survival. Patients were planned to receive 30 Gy in 5 fractions at 2/week, at least 3 days apart, with an additional boost of 6 Gy for small volume disease (< or =3 cm) in suitable patients. Thirty-seven patients were enrolled between August 2004 and March 2006. Median age was 68 (43-87) years, 81% were male and the predominant primary site was oropharynx (32%). The majority (73%) presented with Stage III-IV disease. Thirty-five patients received radiotherapy, 1 died prior to treatment and one refused treatment. Of the 35 patients receiving radiotherapy, 31 (88%) received > or =30 Gy. Of the 35 patients who received treatment the overall objective response was 80%. Grade 3 mucositis and dysphagia were experienced in 9/35 (26%) and 4/35 (11%), respectively. QoL and symptom control were assessable in 21 patients. Thirteen (62%) reported an overall improvement in QoL and 14 (67%) experienced an improvement in pain. The median time to progression and death was 3.9 and 6.1 months, respectively. The "Hypo Trial" regimen provided effective palliative treatment in HNSCC unsuitable for curative treatment. Compliance was excellent and resulted in high response rates, symptom control and improvement in QoL with acceptable toxicity. However, progression free and overall survival was short.
Irradiation of advanced head and neck
  • B Percarpio
  • Fischer
Percarpio B, Fischer JJ. Irradiation of advanced head and neck
Radiotherapy with or without mitomycin c in the treatment of locally advanced head and neck cancer: results of the IAEA multicentre randomised trial
  • Grau
Randomized phase I/II trial of two variants of accelerated fractionated radiotherapy regimens for advanced head and neck cancer: results of RTOG 88-09
  • Fu