Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial.

BACKGROUND: Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with localized high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. OBJECTIVE: The aim of this superiority randomized trial was to compare outcomes of RT combined with either 36 or 18 mo of ADT. DESIGN, SETTING AND PARTICIPANTS: From October 2000 to January 2008, 630 patients with HRPC were randomized, 310 to pelvic and prostate RT combined with 36 mo (long arm) and 320 to the same RT with 18 mo (short arm) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. RESULTS AND LIMITATIONS: With a median follow-up of 9.4 yr, 290 patients had died (147 long arm vs 143 short arm). The 5-yr OS rates (95% confidence interval) were 91% for long arm (88-95%) and 86% for short arm (83-90%), p=0.07. QoL analysis showed a significant difference (p<0.001) in six scales and 13 items favoring 18 mo ADT with two of them presenting a clinically relevant difference in mean scores of ≥10 points. CONCLUSIONS: In localized HRPC, our results support that 36 mo is not superior to 18 mo of ADT. ADT combined with RT can potentially be reduced to 18 mo in selected men without compromising survival or QoL. Thus, 18 mo of ADT appears to represent a valid option in HRPC. PATIENT SUMMARY: In this study, we report outcomes from high-risk prostate cancer patients treated with radiotherapy and either 36 or 18 mo of androgen deprivation therapy. There was no difference in survival between the two groups, with the 18-mo group experiencing a better quality of life.

Should Adjuvant Radiation Therapy Be Systematically Proposed for Male Breast Cancer? A Systematic Review.

BACKGROUND: Guidelines for radiotherapy in male breast cancer (MBC) are lacking. Some extrapolate the results from female breast cancer trials, while others advocate systematic adjuvant irradiation. We evaluated clinical practices and outcomes with respect to radiation therapy in MBC treated with locoregional irradiation in the adjuvant setting using a systematic literature review. MATERIAL AND METHODS: We included studies with data about adjuvant radiotherapy published between 1984 and 2017 and including at least 40 patients. RESULTS: We found 29 retrospective series, 10,065 men were diagnosed with breast cancer; 3-100% (mean=54%) received adjuvant radiotherapy. Tumor size and nodal involvement were the strongest prognostic factors. Approximatively half of all cases had nodal metastases. Radiation therapy improved locoregional control in six series, overall survival in three and distant metastasis-free survival in one. CONCLUSION: MBC is diagnosed at a highly advanced stage and may be linked with poorer outcomes. Adjuvant radiation therapy must, at least, be proposed to men with positive nodes. Despite the large number of cases gathered here, arguments for radiotherapy in other prognostic subgroups (especially in pN0) may exist but are not well supported.

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.

A cosmetic evaluation of breast cancer treatment: a randomized study of radiotherapy boost technique.

PURPOSE: To compare cosmetic results of two different radiotherapy (RT) boost techniques used in the treatment of breast cancer after whole breast radiotherapy and to identify factors affecting cosmetic outcomes. METHODS AND MATERIALS: Between 1996 and 1998, 142 patients with Stage I and II breast cancer were treated with breast conservative surgery and adjuvant RT. Patients were then randomly assigned to receive a boost dose of 15 Gy delivered to the tumor bed either by iridium 192, or a combination of photons and electrons. Cosmetic evaluations were done on a 6-month basis, with a final evaluation at 36 months after RT. The evaluations were done using a panel of global and specific subjective scores, a digitized scoring system using the breast retraction assessment (BRA) measurement, and a patient's self-assessment evaluation. As cosmetic results were graded according to severity, the comparison of boost techniques was done using the ordinal logistic regression model. Adjusted odds ratios (OR) and their 95% confidence intervals (CI) are presented. RESULTS: At 36 months of follow-up, there was no significant difference between the two groups with respect to the global subjective cosmetic outcome (OR = 1.40; 95%CI = 0.69-2.85, p = 0.35). Good to excellent scores were observed in 65% of implant patients and 62% of photon/electron patients. At 24 months and beyond, telangiectasia was more severe in the implant group with an OR of 9.64 (95%CI = 4.05-22.92, p < 0.0001) at 36 months. The only variable associated with a worse global cosmetic outcome was the presence of concomitant chemotherapy (OR = 3.87; 95%CI = 1.74-8.62). The BRA value once adjusted for age, concomitant chemotherapy, and boost volume showed a positive association with the boost technique. The BRA value was significantly greater in the implant group (p = 0.03). There was no difference in the patient's final self-assessment score between the two groups. Three variables were statistically associated with an adverse self-evaluation: an inferior quadrant tumor localization, postoperative hematoma, and concomitant chemotherapy. CONCLUSIONS: Although this trial showed that at 36 months of follow-up, there were no significant differences in the overall global cosmetic scores between the implant boost group and the photon/electron boost group, telangiectasia was more severe and the BRA value was greater in the implant group.

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.