Factors associated with weight loss during radiotherapy in patients with stage I or II head and neck cancer.

BACKGROUND: The purpose of the study was to identify factors associated with weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer. METHODS: This study was conducted as part of a phase III chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Patients' characteristics, dietary intake, health-related quality of life (HRQOL), tumor characteristic, treatment characteristics, and acute adverse effects of RT were evaluated at baseline and during RT. Factors independently associated with weight loss during RT were identified using the multiple linear regression (P ≤ 0.05). RESULTS: The mean weight loss during RT was 2.2 kg (standard deviation, 3.4). In bivariate analyses, the occurrence of adverse effects of RT and most of the HRQOL dimensions evaluated during RT were correlated with weight loss. In the multivariate analysis, eight factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P < 0.001), TNM stage II disease (P = 0.01), higher pre-RT body weight (P < 0.001), dysphagia before RT (P < 0.005), higher mucosa adverse effect of RT (P = 0.03), lower dietary energy intake during RT (P < 0.001), lower score of the digestive dimension on the Head and Neck Radiotherapy Questionnaire (P < 0.001) and a higher score of the constipation symptom on the EORTC QLQ-C30 during RT (P = 0.02). CONCLUSIONS: The results underline the importance of maintaining energy intake in early stage HN cancer patients during RT and the importance of preventing and treating adverse effects.

Prognostic significance of cyclooxygenase-2 overexpression in glottic cancer.

PURPOSE: Cyclooxygenase-2 (COX-2) overexpression has been associated with a poor prognosis in many cancers. However, the role of COX-2 overexpression in head and neck cancers remains undetermined. The objective of this study was to evaluate whether COX-2 is a prognostic factor in glottic cancer. EXPERIMENTAL DESIGN: This study was part of a phase III placebo-controlled randomized trial evaluating the efficacy of alpha-tocopherol in reducing second primary cancers (SPC) in head and neck cancer patients. Immunohistochemical analyses were conducted on pretreatment biopsies of 301 patients with early-stage glottic cancer treated by radiotherapy. The median value of 50% of positive tumor cells was the cutoff point used to define COX-2 overexpression. Outcomes considered in the statistical analysis were recurrence, SPC, and death. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and their 95% confidence intervals (95% CI). RESULTS: The HR associated with COX-2 overexpression was 0.94 (95% CI, 0.55-1.62) for recurrence. The HR associated with SPC was 2.63 (95% CI, 1.32-5.23) for the first 3.5 years of follow-up and 0.55 (95% CI, 0.22-1.32) for the following 3.5 years. The HR associated with COX-2 overexpression was 1.57 (95% CI, 1.01-2.45) for overall mortality. CONCLUSIONS: COX-2 overexpression in glottic cancer was associated with increased overall mortality and an increased risk of SPC during the early follow-up period. Future studies are needed to explain observed effects on SPC. COX-2 expression may prove helpful in defining an individual patient's prognosis.

Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients.

There has been concern that the efficacy of radiation therapy may be reduced when patients smoke or take antioxidant vitamins during treatment. Cancer prevention trials with beta carotene supplements documented adverse effects only among smokers. We conducted a randomized trial with alpha tocopherol (400 IU/day) and beta carotene (30 mg/day) supplements among 540 head and neck cancer (HNC) patients treated by radiation therapy. We examined whether smoking during radiation therapy modified the effects of the supplementation on HNC recurrence and on mortality. During the follow-up, 119 patients had a HNC recurrence and 179 died. Cox models were used to test the interaction between smoking and supplementation and to estimate the hazard ratios (HR) for HNC recurrence and death associated with the supplementation. Cigarette smoking either before or after radiation therapy did not modify the effects of the supplementation. In contrast, the interactions between supplementation and cigarette smoking during radiation therapy were statistically significant for HNC recurrence (p = 0.03), all-cause mortality (p = 0.02) and mortality from the initial HNC (p = 0.04). Among cigarette smokers, the HR were 2.41 (95% CI: 1.25-4.64) for recurrence, 2.26 (95% CI: 1.29-3.97) for all-cause mortality and 3.38 (95% CI: 1.11-10.34) for HNC mortality. All corresponding HR among nonsmokers were close to 1. These results could best be explained by the hypothesis that the combined exposures reduced the efficacy of radiation therapy. Particular attention should be devoted to prevent patients from both smoking and taking antioxidant supplements during radiation therapy.

Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients.

PURPOSE: Many cancer patients take antioxidant vitamin supplements with the hope of improving the outcome of conventional therapies and of reducing the adverse effects of these treatments. A randomized trial was conducted to determine whether supplementation with antioxidant vitamins could reduce the occurrence and severity of acute adverse effects of radiation therapy and improve quality of life without compromising treatment efficacy. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial among 540 head and neck cancer patients treated with radiation therapy. Patients were randomly assigned into two arms. The supplementation with alpha-tocopherol (400 IU/d) and beta-carotene (30 mg/d) or placebos was administered during radiation therapy and for 3 years thereafter. During the course of the trial, supplementation with beta-carotene was discontinued because of ethical concerns. RESULTS: Patients randomly assigned in the supplement arm tended to have less severe acute adverse effects during radiation therapy (odds ratio [OR], 0.72; 95% CI, 0.52 to 1.02). The reduction was statistically significant when the supplementation combined alpha-tocopherol and beta-carotene for adverse effects to the larynx (OR, 0.38; 95% CI, 0.21 to 0.71) and overall at any site (OR, 0.38; 95% CI, 0.20 to 0.74). Quality of life was not improved by the supplementation. The rate of local recurrence of the head and neck tumor tended to be higher in the supplement arm of the trial (hazard ratio, 1.37; 95% CI, 0.93 to 2.02). CONCLUSION: Supplementation with high doses of alpha-tocopherol and beta-carotene during radiation therapy could reduce the severity of treatment adverse effects. However, this trial suggests that use of high doses of antioxidants as adjuvant therapy might compromise radiation treatment efficacy.

Retromolar trigone carcinoma treated by primary radiation therapy: an alternative to the primary surgical approach.

OBJECTIVES: To review our experience in the treatment of retromolar trigone carcinoma with radiotherapy as the primary modality and to evaluate the different factors affecting locoregional control and survival. DESIGN: We retrospectively examined 46 patients with squamous cell carcinoma of the retromolar trigone treated primarily with radiotherapy from January 1, 1973, to June 31, 2002. Four had T1, 21 had T2, 17 had T3, and 4 had T4 lesions; 25 had N0, 15 had N1, 5 had N2, and 1 had N3 disease. The overall stage was I in 3, II in 18, III in 18, and IV in 7 patients. All patients received conventional once-daily fraction radiotherapy as the primary modality of treatment. Three patients received chemotherapy. Overall survival, cause-specific survival, and locoregional control were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify significant prognostic factors for overall survival and locoregional control. RESULTS: The median follow-up was 43 (range, 5-217) months overall and 78 (range, 26-188) months for living patients. The 5-year overall survival and cause-specific survival rates were 47% and 78%, respectively. Favorable prognostic factors for cause-specific survival were a lower tumor stage (univariate and multivariate analysis) and a lower nodal stage (multivariate analysis). The 5-year local control rate was 49% after radiotherapy and 67% after salvage surgery. The 5-year regional control rate was 88%. Favorable prognostic factors were a lower nodal stage and a lower overall stage (univariate analysis). The 5-year locoregional control rate for all patients was 42% after radiotherapy and 70% after salvage surgery. CONCLUSIONS: Given the surgical salvage rate in our series and previous published experience, radiation therapy can be used with curative intent for small retromolar trigone carcinomas (T1-T2 lesions). For advanced stages without bone invasion, consideration for concurrent chemotherapy and radiation therapy might increase previous historical locoregional and survival rates.

Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer.

BACKGROUND: The purpose of the study was to identify predictors of weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer. METHODS: This study was conducted as part of a phase 3 chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Their baseline characteristics, including lifestyle habits, diet, and quality of life, were assessed as potential predictors. Predictors were identified using multiple linear regressions. The reliability of the model was assessed by bootstrap resampling. A receiver operating characteristics curve was generated to estimate the model's accuracy in predicting critical weight loss (>or=5%). RESULTS: The mean weight loss was 2.2 kg (standard deviation, 3.4). Five factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P<.001), higher pre-RT body weight (P<.001), stage II disease (P = .002), dysphagia and/or odynophagia before RT (P = .001), and a lower Karnofsky performance score (P = .028). There was no association with pre-RT lifestyle habits, diet, or quality of life. The bootstrapping method confirmed the reliability of this predictive model. The area under the curve was 71.3% (95% confidence interval, 65.8-76.9), which represents an acceptable ability of the model to predict critical weight loss. CONCLUSIONS: These results could be useful to clinicians for screening patients with early stage HN cancer treated by RT who require special nutritional attention.

Health-related quality of life as a survival predictor for patients with localized head and neck cancer treated with radiation therapy.

PURPOSE: To assess the added prognostic value for overall survival (OS) of baseline health-related quality of life (HRQOL) and of early changes in HRQOL among patients with localized head and neck cancer (HNC) treated with radiation therapy. PATIENTS AND METHODS: All 540 patients with HNC who participated in a randomized trial completed two HRQOL instruments before radiation therapy: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the Head and Neck Radiotherapy Questionnaire. Six months after the end of radiation therapy, 497 trial participants again completed the two HRQOL instruments. During the follow-up, 179 deaths were observed. Multivariate Cox proportional hazards models were used to test whether HRQOL variables, baseline and change, provided additional prognostic value beyond recognized prognostic factors. RESULTS: The baseline EORTC QLQ-C30 physical functioning (PF) score was an independent predictor of OS. The hazard ratio (HR) associated with a 10-point increment in baseline PF was 0.87 (95% CI, 0.81 to 0.94). In multivariate models, the change in HRQOL was significantly associated with OS for most HRQOL dimensions. Among these, PF change was the strongest predictor. The magnitude of the association between PF change and survival decreased over time. At 1 year, the HR associated with a positive PF change of 10 points was 0.75 (95% CI, 0.68 to 0.83). After PF is taken into account, no other HRQOL variable was associated with survival. CONCLUSION: Our findings indicate that both baseline PF and PF change provide added prognostic value for OS beyond established predictors in patients with HNC. Assessing HRQOL could help better predict survival of cancer patients.

Phase 2 study of silver leaf dressing for treatment of radiation-induced dermatitis in patients receiving radiotherapy to the head and neck.

OBJECTIVE: The use of silver leaf dressing is common in the treatment of burn victims owing to its capacity to improve healing and inherent antimicrobial properties. The goal of this study was to investigate its effectiveness in the treatment of radiation-induced dermatitis in a patient population receiving radiotherapy with or without concurrent chemotherapy for various carcinomas of the head and neck compared with our current standard of care, silver sulfadiazine (Flamazine). METHODS: Twelve patients presenting with cancers of the head and neck region with Radiation Therapy Oncology Group (RTOG) grade 2 or more skin toxicity were offered topical treatment of silver sulfadiazine and silver leaf dressing. Each patient applied silver-leaf dressing on one side of the neck and silver sulfadiazine on the other. Three independent observers evaluated the patients based on standardized digital photography and regular follow-up by the treating physician. The sign test was used to evaluate whether the observed difference was statistically significant. RESULTS: There was no improvement in RTOG grade skin toxicity. However, within the same grade, two of three observers agreed on some degree of improvement in the dermatitis with silver leaf dressing compared with silver sulfadiazine. As well, 67% of patients reported improved pain control on the side treated with silver leaf dressing. Sign test analysis indicated that the use of silver-leaf dressing gave significantly superior results when compared with silver sulfadiazine (p = .035). CONCLUSION: Silver leaf dressing does not appear to be superior to our standard treatment for radiation-induced dermatitis when the RTOG grading system is used. It does, however, seem to reduce the severity of reaction within the same grade, accelerate healing, and provide improved pain control over standard treatment. It shows promise regarding symptom control and merits further investigation.

Treatment results of carcinoma in situ of the glottic larynx: 61 patients treated with radiotherapy.

OBJECTIVES: To review the Notre-Dame Hospital experience in the treatment of carcinoma in situ of the glottis by radiotherapy and to evaluate the different factors affecting local control and survival. METHODS: Between January 1990 and June 2002, 61 patients presenting with carcinoma in situ of the glottis were treated with curative intent radiotherapy. No patients received either surgery or chemotherapy in the initial treatment of their cancer. RESULTS: The median follow-up for the entire population was 3.2 years. The local control rate was 96% and 94% at 2 and 5 years, respectively. Overall survival was 100% and 90% at 2 and 5 years, respectively. No statistically significant prognostic factor could be identified either for local control or survival. No patient experienced severe treatment complications or death. CONCLUSION: Radiotherapy offers excellent treatment results for carcinoma in situ of the glottic larynx, with few treatment complications. These results are comparable to those published in the literature and justify our choice of primary radiotherapy for carcinoma in situ of the glottis.

Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients.

There is a debate concerning the effects of antioxidant vitamins during radiation therapy: Can they reduce the adverse effects of therapy without reducing treatment efficacy? We examined whether dietary and plasma beta carotene and alpha tocopherol were related to severe acute adverse effects of radiation therapy and to cancer local recurrence. We conducted a prospective study of 540 head and neck cancer patients treated by radiation therapy. Dietary intakes of beta carotene and alpha tocopherol were measured by a validated food frequency questionnaire and plasma levels were determined. Acute adverse effects of radiation therapy and local recurrence were documented. A higher beta carotene dietary intake was associated with fewer severe acute adverse effects: odds ratio (OR) = 0.61 [95% confidence interval (CI) = 0.40-0.93]. There was a tendency for a similar effect for plasma beta carotene: OR = 0.73 (95% CI = 0.48-1.11). Participants with higher plasma beta carotene had a significantly lower rate of local recurrence (hazard ratio = 0.67; 95% CI = 0.45-0.99). Alpha tocopherol was not related to severe adverse effects or to cancer recurrence. This study suggests that a higher usual dietary beta carotene intake can reduce the occurrence of severe adverse effects of radiation therapy and decrease local cancer recurrence.

Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients.

There has been concern that long-term supplementation with high-dose antioxidant vitamins, especially vitamin E (alpha-tocopherol), may increase all-cause mortality. We conducted a randomized controlled trial with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) supplements among 540 head and neck cancer patients treated by radiation therapy. Supplementation with beta-carotene was discontinued during the trial. The supplements were given during radiation therapy and for 3 additional years. During the follow-up (median 6.5 years), 179 deaths were recorded. All death certificates were obtained. All-cause and cause-specific mortality rates were compared between the 2 arms of the trial by Cox regression. All-cause mortality was significantly increased in the supplement arm: hazard ratio: 1.38, 95% confidence interval 1.03-1.85. Cause-specific mortality rates tended to be higher in the supplement arm than in the placebo arm. Our results concur with previous reports to suggest that high-dose vitamin E could be harmful.

Role of neck dissection following concurrent chemoradiation for advanced head and neck carcinoma.

BACKGROUND: Our primary objective was to determine the role of neck dissection following concomitant chemoradiation (CRT) for advanced stage III-IV head and neck squamous cell carcinoma (HNSCC). METHODS: One hundred eighty-four patients with HNSCC treated with CRT were included. One hundred twenty-three patients reached a regional complete response (CR) after CRT and no neck dissection was performed. Forty-five patients among the 58 who reached a regional partial response (PR) underwent a neck dissection. RESULTS: Overall, regional CR rate after CRT was 68%. Patients who reached a regional CR (no neck dissection) had an overall neck recurrence rate of 5%. Patients with regional PR who underwent a neck dissection had a 7% neck recurrence rate. CONCLUSIONS: Patients with regional CR not followed by a neck dissection have a low rate of neck recurrence. Systematic neck dissection is not mandatory for patients with nodes less than 6 cm reaching a regional CR. For patients with nodes larger than 6 cm, no firm recommendation can be given because of the small number of patients in this series. If the regional response is incomplete, cervical dissection is warranted.

Primary radiotherapy for tonsillar carcinoma: a good alternative to a surgical approach.

OBJECTIVES: To review the Notre-Dame hospital experience in the treatment of tonsillar carcinoma with primary radiotherapy and to evaluate the different factors affecting locoregional control (LRC) and survival. METHODS: We reviewed the records of 164 patients treated consecutively for squamous cell carcinoma of the tonsillar region between January 1990 and June 1999. Our study included 22 T1, 75 T2, 54 T3, and 12 T4 lesions; according to N stage, there were 48 N0, 50 N1, 51 N2, and 15 N3 disease. Overall staging was 6 stage I, 28 stage II, 62 stage III, and 67 stage IV disease. All patients received curative radiotherapy, and 31 patients received chemotherapy either prior to or during treatment with radiotherapy. No patient received surgery as a primary treatment modality. RESULTS: The median follow-up was 4.2 years for all patients and 5.4 years for alive patients. The overall LRC rate was 72% at 5 years. By T and N stage, local and regional control rates at 5 years were as follows: T1, 82%; T2, 74%; T3, 66%; T4, 65%; N0, 77%; N1, 83%; N2, 65%; and N3, 38%. Significant favourable prognostic factors for LRC on univariate analysis were N stage and global stage. On multivariate analysis, the single favourable prognostic factor was N stage. The overall survival (OS) rate was 57% at 5 years. By T and N stage, OS at 5 years was as follows: T1, 62%; T2, 67%; T3, 45%; T4, 22%; N0, 63%; N1, 70%; N2, 46%; and N3, 32%. Significant prognostic factors for OS on univariate analysis were T stage, N stage, and global stage. Favourable prognostic factors for OS on multivariate analysis were T stage and N stage. CONCLUSION: Lower N stage was a favourable prognostic factor for LRC and OS, whereas lower T stage was a favourable prognostic factor on OS. Our results compare favourably with other single-institution surgical series and justify the role of radiotherapy as a primary treatment modality in early tonsillar carcinoma. Concurrent chemotherapy and radiation therapy is currently our standard of care in advanced tonsillar carcinoma.

A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients.

BACKGROUND: Although low dietary intakes of antioxidant vitamins and minerals have been associated with higher risks of cancer, results of trials testing antioxidant supplementation for cancer chemoprevention have been equivocal. We assessed whether supplementation with antioxidant vitamins could reduce the incidence of second primary cancers among patients with head and neck cancer. METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized chemoprevention trial among 540 patients with stage I or II head and neck cancer treated by radiation therapy between October 1, 1994, and June 6, 2000. Supplementation with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) or placebo began on the first day of radiation therapy and continued for 3 years after the end of radiation therapy. In the course of the trial, beta-carotene supplementation was discontinued after 156 patients had enrolled because of ethical concerns. The remaining patients received alpha-tocopherol or placebo only. Survival was evaluated by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: After a median follow-up of 52 months, second primary cancers and recurrences of the first tumor were diagnosed in 113 and 119 participants, respectively. The effect of supplementation on the incidence of second primary cancers varied over time. Compared with patients receiving placebo, patients receiving alpha-tocopherol supplements had a higher rate of second primary cancers during the supplementation period (HR = 2.88, 95% CI = 1.56 to 5.31) but a lower rate after supplementation was discontinued (HR = 0.41, 95% CI = 0.16 to 1.03). Similarly, the rate of having a recurrence or second primary cancer was higher during (HR = 1.86, 95% CI = 1.27 to 2.72) but lower after (HR = 0.71, 95% CI = 0.33 to 1.53) supplementation with alpha-tocopherol. The proportion of participants free of second primary cancer overall after 8 years of follow-up was similar in both arms. CONCLUSIONS: alpha-Tocopherol supplementation produced unexpected adverse effects on the occurrence of second primary cancers and on cancer-free survival.