[show abstract][hide abstract] ABSTRACT: Purpose
The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients.
Materials and methods
A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for use of each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible.
Forty-one papers were reviewed. There was sufficient evidence to recommend the use of benzydamine mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving moderate-dose radiation therapy (up to 50 Gy), without concomitant chemotherapy. A new suggestion was developed against the use of misoprostol mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving radiation therapy. Positive results were reported for some other anti-inflammatory agents. However, no guidelines were able to be developed for any other agents due to insufficient and/or conflicting evidence.
The use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. Additional well-designed studies are needed to examine the use of this class of agents for oral mucositis.
Supportive Care Cancer 11/2013; · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: Health-related quality of life (HRQOL) is a key aspect for chronic myeloid leukemia (CML) patients. The aim of this study was to develop a disease-specific HRQOL questionnaire for patients with CML to supplement the European Organization for Research and Treatment of Cancer (EORTC)-QLQ C30.
The process followed a predefined and systematic stepwise iterative process as defined by the EORTC guidelines for questionnaire development. The process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2) operationalization of the HRQOL issues into a set of items, and (3) pretesting the questionnaire for relevance and acceptability. Descriptive statistics and psychometric analyses were also performed.
Overall, 655 CML patients were enrolled in 10 countries including the USA and countries in Europe and Asia. Interviews with health-care professionals experienced in CML (n = 59) were also conducted. Results from the interviews, clinical experiences, and statistical analyses were used to develop the EORTC QLQ-CML24. The final module consists of 24 items assessing the following aspects: symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life. Internal consistency, assessed with Cronbach's alpha coefficients, ranged from 0.73 to 0.83 for the proposed scales.
The EORTC QLQ-CML24 is an internationally developed HRQOL questionnaire for CML patients, and its implementation in clinical research and practice can provide important information to facilitate clinical decision-making.
Quality of Life Research 09/2013; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: We report the clinical features and management outcomes in 7 patients with everolimus-related stomatitis. STUDY DESIGN: Fifteen women with hormone-receptor-positive advanced breast cancer receiving everolimus combined with exemestane were prospectively evaluated to assess the development of stomatitis. Oral ulcers were diagnosed based on established criteria. RESULTS: Seven patients developed stomatitis (46.6%). All patients were treated with topical dexamethasone solution, while everolimus was temporarily discontinued in 4 patients. Stomatitis resolved within 1-2 weeks. Two of the 4 patients, who had interrupted everolimus, developed recurrent stomatitis following drug resume and everolimus was again discontinued and restarted after 2 weeks. To date, 5 patients receive everolimus in full dose. The 2 patients, who developed recurrent stomatitis, received a reduced dose. CONCLUSIONS: Everolimus-related oral ulcers were frequent and led to dose modifications. Controlled trials, endorsing a consensus in terminology, are needed to evaluate measures on prevention and management of this unique toxicity.
Oral surgery, oral medicine, oral pathology and oral radiology. 05/2013;
[show abstract][hide abstract] ABSTRACT: PURPOSE: The EORTC QLQ-H&N35 (H&N35) is widely used to measure quality of life in head and neck cancer patients. The aims of this study were to obtain insight into a) the languages in which the H&N35 has been used and the psychometric properties in those languages, b) the study designs, and c) its acceptance by patients and investigators. METHODS: A systematic literature review was performed searching for all original papers that had used at least one item of the H&N35. Identified papers were read and the information about methodological issues abstracted statistically analysed. RESULTS: A total of 136 papers were identified. The H&N35 was administered in 19 different languages in 27 countries. The study design was cross-sectional in the majority of studies (53 %), prospective cohort studies (31 %), phase-II-trials (7 %), phase-III-trials (6 %) and case-control studies (1 %). The scales with the highest percentages of missing values were Sexuality (11.5 %) and Speech (7 %). The median Cronbach's alpha of the multi-item scales ranged from 0.61 (Senses) to 0.93 (Sexuality). Construct validity was rarely investigated. On average, 12 scales (range 0-18) of the instrument were used by the investigators. The scale most often used was swallowing (in 85 % of studies) and least often used was Weight Gain (39 %). CONCLUSION: The H&N35 is widely used throughout the world, mainly in observational studies, and has demonstrated robust psychometric features in different languages. However, some methodological problems reported imply that the instrument can be improved in some areas.
Quality of Life Research 11/2012; · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. RESULTS: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. CONCLUSION: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis.
Supportive Care in Cancer 10/2012; · 2.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Assessment of oral and dental problems is seldom routine in clinical oncology, despite the potential negative impact of these problems on nutritional status, social function and quality of life (QoL). The aim was to develop a supplementary module to the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) focusing on oral health and related QoL issues in all cancer diagnoses.
The module development followed the EORTC guidelines. Phases 1&2 were conducted in France, Germany, Greece, Netherlands, Norway and United Kingdom, while seven countries representing seven languages were included in Phase 3.
Eighty-five QoL-items were identified from systematic literature searches. Semi-structured interviews with health-care professionals experienced in oncology and oral/dental care (n=18) and patients (n=133) resulted in a provisional module with 41 items. In phase 3 this was further tested in 178 European patients representing different phases of disease and treatment. Results from the interviews, clinical experiences and statistical analyses resulted in the EORTC QLQ-OH17. The module consists of 17 items conceptualised into four multi-item scales (pain/discomfort, xerostomia, eating, information) and three single items related to use of dentures and future worries.
This study provides a useful tool intended for use in conjunction with the EORTC QLQ-C30 for assessment of oral and dental problems. The increased awareness may lead to proper interventions, thereby preventing more serious problems and negative impact on QoL. The reliability and validity, the cross-cultural applicability and the psychometric properties of the module will be tested in a larger international study.
European journal of cancer (Oxford, England: 1990) 05/2012; 48(14):2203-11. · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of this study was to investigate the health-related quality of life (HRQOL) aspects valued the most by patients with chronic myeloid leukemia (CML) receiving targeted therapies (TT), and to compare their perception with that of health-care professionals' (HCPs). Semi-structured interviews were conducted with 137 CML patients receiving TT from five different countries. An additional sample of 99 CML patients, completing an online interview, was considered for supportive analyses. A sample of 59 HCPs from 12 countries also participated in the study. Patients and HCPs were asked to rate and rank the importance of a predefined list of 74 HRQOL aspects of potential relevance for CML patients. Patients and HCPs agreed that the following five aspects are most important: fatigue, muscle cramps, swelling, worries, and uncertainty about health condition in the future, and importance of social support in coping with the disease. However, the difference in rankings between the two groups was substantial with respect to other HRQOL aspects investigated. Patients valued some issues related to symptoms much higher than HCPs, thus suggesting that a better symptom management could be the crucial aspects to improve HRQOL of CML patients.
Annals of Hematology 04/2012; 91(9):1371-81. · 2.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is emerging evidence that oral mucositis/stomatitis is a common adverse effect of sunitininb antiangiogenic therapy in patients with metastatic renal cell carcinoma (mRCC). In addition, a case of sunitinib-related jaw osteonecrosis was recently described. We report on 2 patients with mRCC treated with sunitinib. The first patient, a 19-year-old woman, treated with cisplatin and sunitinib, presented with oral pain, malodor, spontaneous and continuous gingival bleeding, and painful necrotic ulcerations clinically resembling necrotizing ulcerative gingivitis (NUG). Suntinib-related stomatitis and bleeding were considered cumulative to NUG symptoms. The second patient, a 64-year-old woman, treated with sunitinib only, complained of mandibular pain. Sunitinib-related jaw osteonecrosis was diagnosed. Gingival bleeding and soft tissue necrosis, as well as jaw osteonecrosis may develop as adverse events of sunitinib use. Antiangiogenic therapies are increasingly used in the treatment of cancers. The presented cases are aimed to alert health care professionals on adverse oral events.
[show abstract][hide abstract] ABSTRACT: The objectives of this study were to define the incidence, pain, and healing in cancer patients treated with intravenous bisphosphonates.
The study included long-term follow-up of 99 bisphosphonate-using patients (group A) and conservative treatment of 67 patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ, group B) using 3 antibiotic schemes and oral hygiene.
The frequency of zoledronic acid single-agent use was 85.9% and 69.8% in group A and B, respectively. Median follow-up was 13 months (group A) and 16 months (group B). Two patients in group A developed BRONJ (2%). Of those with BRONJ in group B who completed follow-up, healing occurred in 14.9% (7/47) and pain subsided in 80.9% (38/47). Healing was significant in patients who received pamidronate followed by zoledronic acid (P = .023) and with BRONJ stages 0 and stage I (P = .003).
This case series suggests that oral hygiene and conservative antibiotic therapy play a role in healing and pain alleviation in BRONJ. Oral hygiene and follow-up may decrease incidence of BRONJ.
[show abstract][hide abstract] ABSTRACT: Goal of work: This study compared the severity of oral mucositis, pain and xerostomia during and at the completion of radiotherapy in head and neck cancer patients who had received antifungal and antiviral treatment. Patients: The study included 135 patients. Mean total radiotherapy dose was 62.4 Gray. Chemotherapy was administered to 47% of patients. Methods: Oral mucositis was scored weekly, while patients self-evaluated their pain and xerostomia. Cytology smears for the assessment of herpetic infection complicating the ulcers of mucositis were taken from 46 patients. Systemic antifungals and antivirals were administered during radiotherapy, upon clinical, presumptive diagnosis of candidiasis and herpetic infection. Antifungals and antivirals were continued to the end of radiotherapy. Results: Radiotherapy was completed within the preplanned time in 117 patients (87%). During radiotherapy, the prevalence of severe mucositis, pain and xerostomia was 57%, 43% and 29% respectively, and was significantly reduced to 33%, (P<0.001), to 24%, (P<0.001), and to 18%, (P<0.05) at the end of radiotherapy. Antifungals and antivirals were utilized in 70% and 71% of patients, respectively. Viral cytology was positive in 14 of 46 (30.4%) patients. Conclusions: The significant reduction of severe oral mucositis, pain and xerostomia at time of completion of radiotherapy, as compared to during the course of radiotherapy, after the treatment and prevention of candidiasis and herpes, denotes an important role of these infections in radiation-induced mucositis. Limitations of the study are the practical issues of the lack of the verification of the fungal status before and after treatment and of the verification of the viral status in only 47.9% (46 of 96) of the patients with a clinical suspicion of herpetic infection. A controlled study is needed to investigate and further clarify the role of antifungal and antiviral prophylaxis relative to oral mucositis, pain and xerostomia during head and neck RT.
[show abstract][hide abstract] ABSTRACT: The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections.
Thirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization.
For all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pre-treatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care.
There is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal agents are less efficacious, suggesting a need for better topical agents.
Supportive Care in Cancer 05/2010; 18(8):985-92. · 2.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Goal of work: To compare the severity of oral mucositis, pain and xerostomia in head and neck cancer patients, who received radiotherapy with cisplatin and cetuximab to that of patients who received radiotherapy with cisplatin alone. Patients: Forty-nine head and neck cancer patients entered the study. Twenty-five patients (Group A) received radiotherapy and cisplatin. Twenty-four patients (Group B) received radiotherapy, cisplatin, and cetuximab. Methods: Oral mucositis was recorded weekly, according to EORTC/RTOG criteria. Pain and xerostomia were assessed using a 10cm visual analogue scale. Antifungal and antiviral treatment and prophylaxis were administered during RT to both groups. Results: During chemoradiotherapy, severe mucositis, pain and xerostomia were observed in 60%, 64% and 52% respectively in Group A, while the same symptoms were observed in 79%, 58% and 29% respectively in Group B. The differences between the two groups were not statistically significant. At the end of chemoradiotherapy, severe mucositis, pain and xerostomia were recorded in 24%, 32% and 32% in Group A and 37%, 21% and 17% respectively in Group B. The differences between the two groups were, again, statistically not significant. Neither significant differences were found between the two groups with respect to the use of antifungal and antiviral treatment, radiotherapy interruptions and weight loss. In both groups, oral mucositis, pain and xerostomia were significantly reduced at the end of radiotherapy as compared to those during RT, following the anti-infectious treatment and prophylaxis. Conclusion: Cetuximab, added to cisplatin/radiotherapy, did not increase the severity of oral mucositis, pain and xerostomia, in head and neck cancer patients, with limitations of the study design and its limited number of patients.
[show abstract][hide abstract] ABSTRACT: A breast cancer patient with skeletal metastases was treated with only one i.v. dose of ibandronate in March of 2005 and subsequent doses of oral ibandronate 50 mg daily. One year after the i.v. infusion, the patient complained of oral pain under her lower denture. After several negative attempts from her dentist to control the pain and adjust the denture, the patient was diagnosed with bisphosphonate-associated osteonecrosis (BON) of the mandible. The use of ibandronate, a potent bisphosphonate, is increasing worldwide. Prescribing oncologists should be aware of the potential for the development of new cases of BON in a similar fashion as with zoledronic acid.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the expression of pro-apoptotic protein p53 and anti-apoptotic proteins BCl-2 and MCl-1, as well as the expression of pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta) in patients developing mucositis during radiotherapy for head and neck cancer.
Thirty-five patients receiving radiotherapy for head/neck cancer were included in this study. Patients were examined before radiotherapy. Oral mucositis was recorded weekly during radiotherapy. Cytologic smears from the oral cavity were taken with a brush. Immunocytochemical staining was performed by the use of p53, BCl-2, MCl-1 TNF and IL-1beta monoclonal antibodies.
P53 was expressed in 1 of 15 smears before the initiation of radiotherapy (6.5%) compared to 3 of 7 smears from patients with grade III mucositis (43%) during radiotherapy. BCl-2 was expressed in 15 of 15 smears before radiotherapy (100%) and in three of seven patients with grade III mucositis (43%) during radiotherapy. MCl-1 was expressed in 10 of 14 samples before radiotherapy (71.5%) and in two of seven patients with grade III (28.5%) mucositis during radiotherapy. TNF was expressed in 9 of 14 patients before radiotherapy (64%) and in six of seven patients with grade III mucositis during radiotherapy (86%). IL-1beta was detected in 7 of 14 patients before radiotherapy (50%) compared to 6 of 7 patients with grade III mucositis during radiotherapy (86%).
Our preliminary results indicate an induction of apoptosis and inflammation in the oral mucosa in patients developing mucositis during radiotherapy for head/neck cancer.
Supportive Care Cancer 02/2008; 16(9):1025-33. · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to investigate the incidence of herpes simplex virus-1 (HSV-1) infection in mucositis during head and neck cancer radiotherapy.
Sixty patients with malignant head and neck tumor, eligible to receive radiotherapy, who were referred to the Dental Oncology Unit, entered the study. Sixteen patients (26.6%) received concomitant chemotherapy. Mucositis was recorded weekly. Smears taken from the ulcers of mucositis grade 2, or 3, or 4 were stained with Papanicolaou and alkaline phosphatase/antialkaline phosphatase immunocytochemical method to identify HSV-1.
Forty-eight of all 60 patients developed ulcerative mucositis. Smear was available from 29 of 48 patients with ulcerations. HSV-1 infection was identified in 14 of 29 smears available (48.2%). Mucositis healed or was reduced after 1 week of antiviral treatment in 11 of those 14 HSV-1-positive patients; 3 patients responded to 1 g/day of valacyclovir, 7-2 g/day, and 1 patient responded to i.v. acyclovir. Ulcerations recurred after quitting antivirals. Three patients did not respond to 1 g/day of valacyclovir. No HSV-1-negative patient responded to acyclovir (P = 0.000).
HSV-1 was isolated from 14 of 29 available smears taken from 48 patients with ulcerative mucositis. The incidence of HSV-1 infection during radiotherapy was estimated as being 14 of all 48 patients at risk (29.1%). Healing or reduction in the grade of mucositis after antivirals in HSV-1 positive patients, combined with the negative response to antivirals in HSV-1 negative patients, denoted that HSV-1 infection was a component of ulcerative radiation mucositis in those HSV-1-positive patients.
Supportive Care Cancer 08/2006; 14(7):753-62. · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy.
Sixty-three patients, with malignant head and neck tumor, eligible to receive radiotherapy, entered the study. Thirty-four patients (group A) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients, who received radiotherapy alone (group B). The two groups were similar in terms of patients and radiotherapy characteristics. Smear to test for Candida carriage was taken before and after radiotherapy. Oral candidiasis was diagnosed using the criteria described before. Oral mucositis was recorded according to EORTC/RTOG criteria.
A significant reduction of severe mucositis at the end of radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017) was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a significant reduction of Candida carriage of 40.7% (p=0.001).
Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients. The current study provides data on the build of a randomized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy.
Supportive Care Cancer 02/2006; 14(1):44-51. · 2.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate the association between the prevalence of oral lesions and highly active antiretroviral therapy (HAART) including a protease inhibitor (PI).
Ninety-five consecutive patients, attending an AIDS Unit, in Greece entered the study. Fourty-four patients were receiving PI- HAART, 14 patients were on double antiretroviral therapy, and 37 patients were not receiving antiretroviral therapy at the time of oral examination. Oral lesions were diagnosed by established presumptive clinical criteria.
Oral lesions were scored. CD4 counts and viral load were determined and related to the prevalence of oral lesions.
Oral lesions, and specifically oral candidiasis, were significantly reduced (P < 0.001) in patients receiving PI-HAART. Oral lesions were significantly increased in patients with CD4 counts <200 cells microl(-1) and viral load >20,000 copies ml(-1) (P < 0.001). The percentage of patients, with lesions on PI-HAART, and with CD4 < 200 and viral load >20,000 was 1.5 times lower (37.5%vs 58.8%, P < 0.001) than that of patients not receiving antiretroviral therapy, but with similar immune and viremic status.
Oral lesions were significantly reduced in patients on PI-HAART. A direct anticandidal effect of PI was suggestive and seemed to have accounted, beyond the HAART-related immune reconstitution, for the reduction of candidiasis and all other oral lesions.