[Show abstract][Hide abstract] ABSTRACT: To estimate dose-response relationship using dynamic quantitative (99m)Tc-pertechnate scintigraphy in head-neck cancer patients treated with parotid-sparing conformal radiotherapy.
Dynamic quantitative pertechnate salivary scintigraphy was performed pre-treatment and subsequently periodically after definitive radiotherapy. Reduction in salivary function following radiotherapy was quantified by salivary excretion fraction (SEF) ratios. Dose-response curves were modeled using standardized methodology to calculate tolerance dose 50 (TD50) for parotid glands.
Salivary gland function was significantly affected by radiotherapy with maximal decrease in SEF ratios at 3-months, with moderate functional recovery over time. There was significant inverse correlation between SEF ratios and mean parotid doses at 3-months (r = -0.589, p < 0.001); 12-months (r = -0.554, p < 0.001); 24-months (r = -0.371, p = 0.002); and 36-months (r = -0.350, p = 0.005) respectively. Using a post-treatment SEF ratio <45% as the scintigraphic criteria to define severe salivary toxicity, the estimated TD50 value with its 95% confidence interval (95%CI) for the parotid gland was 35.1Gy (23.6-42.6Gy), 41.3Gy (34.6-48.8Gy), 55.9Gy (47.4-70.0Gy) and 64.3Gy (55.8-70.0Gy) at 3, 12, 24, and 36-months respectively.
There is consistent decline in parotid function even after conformal radiotherapy with moderate recovery over time. Dynamic quantitative pertechnate scintigraphy is a simple, reproducible, and minimally invasive test of major salivary gland function.
[Show abstract][Hide abstract] ABSTRACT: Aims:
Treatment intensification either by using concurrent chemoradiotherapy (CCRT) or altered fractionation radiotherapy (AFRT) improves outcomes of locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The superiority of one approach over the other, however, remains to be firmly established. The aim of the present study was to compare outcomes of CCRT versus AFRT in the definitive non-surgical management of locoregionally advanced HNSCC for evidence-based decision making.
Materials and methods:
An electronic search of Medline via PubMed was conducted with no language, year, or publication status restrictions. The Cochrane Central Register of Controlled Trials (CENTRAL) and Database of Abstracts of Reviews of Effectiveness (DARE) were also searched electronically. Only randomised controlled trials assigning HNSCC patients randomly to conventionally fractionated CCRT or AFRT alone were included. Data were extracted independently by two reviewers and pooled using the Cochrane methodology for meta-analysis and expressed as a hazard ratio with 95% confidence intervals. Overall survival was the primary outcome of interest, whereas disease-free survival, locoregional control and toxicity were secondary end points.
Five randomised controlled trials (involving 1117 patients and 627 deaths) directly comparing conventionally fractionated CCRT with AFRT alone were included. The risk of bias in included studies was low for efficacy outcomes, but high for toxicity outcomes. The overall pooled hazard ratio of death was 0.73 (95% confidence interval = 0.62-0.86), which significantly favoured conventionally fractionated CCRT over AFRT alone (P < 0.0001). Similarly, disease-free survival (hazard ratio = 0.79, 95% confidence interval = 0.68-0.92; P = 0.002) and locoregional control (hazard ratio = 0.71, 95% confidence interval = 0.59-0.84; P < 0.0001) were significantly improved with CCRT. There were no significant differences in the incidence of severe acute toxicity (dermatitis and mucositis) between the two approaches of treatment intensification. Late xerostomia was significantly increased with CCRT. Significant haematological toxicity and nephrotoxicity were seen exclusively with chemotherapy.
There is moderate quality evidence that conventionally fractionated CCRT improves survival outcomes compared with AFRT alone in the definitive radiotherapeutic management of locoregionally advanced HNSCC. No form of acceleration can potentially compensate fully for the lack of concurrent chemotherapy.
[Show abstract][Hide abstract] ABSTRACT: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1).
The aim of this study was to evaluate prognostic heterogeneity in the stage III category.
An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011.
Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2).
The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.
Annals of Surgical Oncology 08/2015; DOI:10.1245/s10434-015-4842-3 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methods:
A total of 32 patients with painful skeletal metastases were prospectively evaluated (26 men and 6 women; mean age of 46.19 years; age range: 33-84 years). Patients were divided in two groups, Patients treated with (177)Lu-EDTMP (n = 16) and those treated with (153)Sm-EDTMP (n = 16). In both the groups, patients were treated with dose of 37MBq/kg body weight for both the radionuclide (dose range of (177)Lu-EDTMP varied from 1295 MBq to 2701 MBq depending on the weight of patient, whereas in (153)Sm-EDTMP the dose range varied from 1258 MBq to 2553 MBq). The following evaluation scores were adopted to examine the efficacy: [i] Analgesic score, [ii] pain scale (visual analogue scale or VAS), [iii] quality of life evaluation using 3 assessment scales (EORTC, Karnofsky and ECOG assessment scales), [iv] bone proliferation marker (estimation of bone alkaline phosphatase or BAP). The hematological toxicity was evaluated using NCI-Common Terminology Criteria for Adverse Events (CTCAE) and was compared between both groups at baseline and each monthly till 3 months post therapy. For the assessment of pain response post-therapy, a pre-defined criteria was followed used in this study protocol that considered both the VAS and analgesic score change on a sliding scale (rather than a single parameter or an absolute value), and the response was subdivided into 4 categories: complete response (CR), partial response (PR), minimal response (MR) and no-response (NR).
The overall pain relief in patients treated with (177)Lu-EDTMP was 80%. Among the responders, 50% of patients had complete response (CR), 41.67 % had partial response (PR) and 8.33% had minimal response (MR). The overall pain relief in patients treated with (153)Sm-EDTMP was 75%. Among these, 33.33% of patients had complete response (CR), 58.33% had partial response (PR) and 8.33% had minimal response (MR). The difference in pain relief between these two groups was not significant (P = 1.000). There was significant improvement in quality of life post therapy at 3 month in both group of patients as assessed by ECOG (P =0.014 and 0.005) and Karnofsky indices (P =0.007 and 0.023) respectively for (177)Lu-EDTMP and (153)Sm-EDTMP. There was significant improvement in quality of life (pain free survival) post therapy at 3 month in both group of patients as assessed by EORTC QLQ BM22 score (P = 0.004 and <0.001) respectively for (177)Lu-EDTMP and (153)Sm-EDTMP. Bone proliferation marker in responders showed significant reduction in both groups [(177)Lu-EDTMP (P =0.008) and (153)Sm-EDTMP (P =0.019)], parallel to the clinical response. In patients treated with (177)Lu-EDTMP non-serious (Grade I / II) anemia, leucopenia and thrombocytopenia was noted in 46.67%, 46.67% and 20% respectively. In patients treated with (177)Lu-EDTMP serious (Grade III / IV) anemia, leucopenia and thrombocytopenia was noted in 20%, 6.67% and 0% respectively. In patients treated with (153)Sm-EDTMP non-serious (Grade I / II) anemia, leucopenia and thrombocytopenia was noted in 62.5%, 31.25% and 18.75% respectively. In patients treated with (153)Sm-EDTMP serious (Grade III / IV) anemia, leucopenia and thrombocytopenia was noted in 18.75%, 0% and 6.25% respectively. Only 1 patient treated with (153)Sm-EDTMP showed Grade IV thrombocytopenia, however no blood transfusion was required. No statistically significant difference noted in non-serious toxicity between two groups with respect to anemia (P = 0.571), leucopenia (P = 0.511) and thrombocytopenia (P = 0.561). No statistically significant difference noted in serious toxicity between two groups with respect to anemia (P = 0.671), leucopenia (P = 0.334) and thrombocytopenia (P = 0.739). 3 out of 12 responders (25% of the responders) treated with (177)Lu-EDTMP reported incidence of flare phenomenon, on 3rd day post therapy and 1 (8.33%) reported on 5th day post therapy, showing no response to therapy. In (153)Sm-EDTMP group, 2 out of 12 responders (16.66% of the responders) reported incidence of flare phenomenon, reported on 3rd day post therapy.
The present study documented a similar pain response efficacy of (177)Lu-EDTMP coupled with improvement in the quality of life when compared to that of (153)Sm-EDTMP. Similar hematological toxicity profile and absence of renal toxicity demonstrated with (177)Lu-EDTMP would indicate that this agent is a feasible and safe alternative to (153)Sm-EDTMP for treatment of painful skeletal metastasis with minimal side effects especially in the setting of centers having no nearby accessibility for (153)Sm-EDTMP because of its longer half life. This is an important consideration taking into account that (177)Lu is a popular radionuclide for PRRT in many centres across the world.
Journal of Nuclear Medicine 08/2015; 56(10). DOI:10.2967/jnumed.115.155762 · 6.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionBreath-holding (BH) technique is used for reducing the intrafraction-tumour motion in mobile lung tumours treated with radiotherapy (RT). There is paucity of literature evaluating differences in BH times in various phases of respiration in patients with lung cancer.Methods
One hundred consecutive patients with lung cancer planned for radical RT/chemoradiation were accrued in the study. Eighty-seven patients were eligible for analysis at RT conclusion. Baseline pulmonary function test (PFT) were performed in all patients, and respiratory training was given from the day of RT planning. Deep inspiration breath hold (DIBH), deep expiration breath hold (DEBH) and mid-ventilation breath hold (MVBH) were recorded manually with a stopwatch for each patient at four time points (RT planning/baseline, RT starting, during RT and RT conclusion).ResultsMedian DIBH times at RT planning, RT starting, during RT and RT conclusion were 21.2, 20.6, 20.1 and 21.1 s, respectively. The corresponding median DEBH and MVBH times were 16.3, 18.2, 18.3, 18.5 s and 19.9, 20.5, 21.3, 22.1 s, respectively. Respiratory training increased MVBH time at RT conclusion compared to baseline, which was statistically significant (19.9–22.1 s, P = 0.002). DIBH or DEBH times were stable at various time points with neither a significant improvement nor decline. Among various patient and tumour factors Forced Vital Capacity pre-bronchodilation (FVCpre) was the only factor that consistently predicted DIBH, DEBH and MVBH at all four time points with P value <0.05.ConclusionsBH was well tolerated by most lung cancer patients with minimum median BH time of at least 16 s in any of the three phases of respiration. Respiratory training improved MVBH time while consistently maintaining DIBH and DEBH times throughout the course of radiotherapy.
Journal of Medical Imaging and Radiation Oncology 07/2015; 59(4). DOI:10.1111/1754-9485.12324 · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Whether patients with early-stage oral cancers should be treated with elective neck dissection at the time of the primary surgery or with therapeutic neck dissection after nodal relapse has been a matter of debate.
In this prospective, randomized, controlled trial, we evaluated the effect on survival of elective node dissection (ipsilateral neck dissection at the time of the primary surgery) versus therapeutic node dissection (watchful waiting followed by neck dissection for nodal relapse) in patients with lateralized stage T1 or T2 oral squamous-cell carcinomas. Primary and secondary end points were overall survival and disease-free survival, respectively.
Between 2004 and 2014, a total of 596 patients were enrolled. As prespecified by the data and safety monitoring committee, this report summarizes results for the first 500 patients (245 in the elective-surgery group and 255 in the therapeutic-surgery group), with a median follow-up of 39 months. There were 81 recurrences and 50 deaths in the elective-surgery group and 146 recurrences and 79 deaths in the therapeutic-surgery group. At 3 years, elective node dissection resulted in an improved rate of overall survival (80.0%; 95% confidence interval [CI], 74.1 to 85.8), as compared with therapeutic dissection (67.5%; 95% CI, 61.0 to 73.9), for a hazard ratio for death of 0.64 in the elective-surgery group (95% CI, 0.45 to 0.92; P=0.01 by the log-rank test). At that time, patients in the elective-surgery group also had a higher rate of disease-free survival than those in the therapeutic-surgery group (69.5% vs. 45.9%, P<0.001). Elective node dissection was superior in most subgroups without significant interactions. Rates of adverse events were 6.6% and 3.6% in the elective-surgery group and the therapeutic-surgery group, respectively.
Among patients with early-stage oral squamous-cell cancer, elective neck dissection resulted in higher rates of overall and disease-free survival than did therapeutic neck dissection. (Funded by the Tata Memorial Centre; ClinicalTrials.gov number, NCT00193765.).
New England Journal of Medicine 05/2015; 373(6). DOI:10.1056/NEJMoa1506007 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT: Abstract No: eEdE-91 Submission Number: 1398 Authors: S Arya1, A Kawthalkar2, J Agarwal1 Institutions: 1Tata Memorial Hospital, Mumbai, India, 2Tata Memorial Hospital, Mumbai, Maharashtra Purpose: 1. To review literature on the best imaging method/methods to detect neck node metastases in head and neck squamous cell cancers (HNSCC). 2. To identify the clues and pitfalls in detecting neck node metastases with each imaging method. 3. To provide a detailed checklist of features to be studied in neck nodes in cases of HNSCC with various imaging methods. Approach/Methods: Numerous imaging methods have been studied to detect metastases in the neck in HNSCC. This exhibit will collate evidence from literature including meta-analyses evaluating ultrasound (US), US-guided fine needle aspiration (gFNA) , CT, MRI, diffusion-weighted and dynamic contrast-enhanced MRI, PET CT and Sentinel node biopsy for detecting neck node metastases in HNSCC and identify the best imaging method supported by literature currently. Features suggestive of metastatic nodes on each imaging method will be described along with pitfalls of each method. Findings/Discussion: Neck node metastases is the single most important prognostic factor for head neck squamous cancers. Average incidence of occult metastases in neck nodes is about 15% in all HNSCC. Expectations of imaging to identify these have fuelled investigation into numerous imaging methods. Several retrospective studies, few prospective studies and few meta-analyses provide evidence regarding US, US gFNA, CT, MRI including advanced MRI and PET CT and conclude that all these methods have comparable sensitivity and specificity to detect metastatic neck nodes. However many of the studies involve both the clinically negative and positive necks while ideally the accuracy of imaging needs to be tested in the clinically negative neck. Currently none of the methods are comparable to surgical staging of the neck (neck dissection) in the clinically negative neck. Sentinel node biopsy has been evaluated in oral cancers and has a promising role to detect neck node metastases. Despite these limitations, the radiologist should be a) aware of clues that suggest metastatic nodes on various imaging methods and b) also provide information to decide resectability of nodes and to optimally plan radiation therapy in the clinically positive neck. Summary/Conclusion: This exhibit aims to familiarize the radiologist with the clinicians' issues in staging the neck, an evidence-based review of the accuracy of various imaging methods, the clues and pitfalls in imaging for neck nodes and a checklist for reporting on neck nodes in HNSCC.
ASNR 2015; 04/2015
[Show abstract][Hide abstract] ABSTRACT: Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.
Indian Journal of Cancer 12/2014; 51(3):231-235. DOI:10.4103/0019-509X.146734 · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2–12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012.
Patients and methods
All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS.
721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p = 0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59–25.21 months) and 8.16 months (95%, CI 7.57–8.76) in patients treated with non surgical treatment (p = 0.0001).
In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients.