Impact of high-dose chemotherapy on the ability to deliver subsequent local-regional radiotherapy for breast cancer: analysis of Cancer and Leukemia Group B Protocol 9082.

PURPOSE: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary nodes. METHODS AND MATERIALS: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. RESULTS: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID. CONCLUSION: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.

Interruptions of once-daily thoracic radiotherapy do not correlate with outcomes in limited stage small cell lung cancer: analysis of CALGB phase III trial 9235.

PURPOSE: Retrospective data suggests prolonging the time to complete thoracic radiotherapy (TRT) may negatively impact tumor control and survival in limited stage small cell lung cancer (LSCLC). We examined the association between TRT duration and outcomes on a prospective phase III study. MATERIAL AND METHODS: This review included 267 patients who received protocol TRT on a phase III CALGB LSCLC study assessing the addition of tamoxifen to standard chemo-radiotherapy. TRT, to a planned dose of 50Gy in 2Gy daily fractions, was initiated with the fourth chemotherapy cycle. TRT interruptions were mandated for hematologic toxicity (granulocytes<1000/mm3 or platelets<75,000/mm3) and esophageal toxicity (dysphagia necessitating intravenous hydration). RESULTS: TRT interruptions > or =3 days occurred in 115 patients (43%), most frequently during the 4th week of TRT, and did not differ between treatment arms. Hematologic toxicity and esophageal toxicity were the most frequent indications for interrupting TRT. Variables including advanced age (>70 years), gender, race, or radiotherapy treatment volume did not predict for TRT interruptions. Overall survival (OS) and local tumor control did not correlate with the administration of TRT interruptions or with TRT duration. CONCLUSION: Toxicity mandated interruptions of conventional dose, once-daily, TRT may not adversely affect outcomes for patients receiving TRT concurrent with chemotherapy (cycle 4) for LSCLC. The implications for accelerated or high dose TRT regimens are not clear.

Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: cancer and leukemia group B 9344.

PURPOSE: We compared radiotherapy (RT) delivery and locoregional control in patients with node-positive breast cancer randomly assigned on Cancer and Leukemia Group B 9344 to receive adjuvant doxorubicin/cyclophosphamide (AC) with patients assigned to receive AC followed by paclitaxel (AC+T). METHODS: Eligible patients were randomly assigned to receive adjuvant AC versus AC+T chemotherapy. RT was required if breast-conserving surgery was performed but was elective after mastectomy. Information about RT delivery was retrospectively collected. Cumulative incidence of locoregional recurrence (LRR), use of elective RT, and RT delivery were compared between treatment arms. RESULTS: For patients treated with breast-conserving surgery and RT, the 5-year cumulative incidence of isolated LRR was 9.7% in the AC arm and 3.7% in the AC+T arm (P = .04) and of LRR as any component of failure was 12.9% versus 6.1%, respectively (P = .04). Although LRR rates in patients who did not receive postmastectomy RT were lower in the AC+T arm, the difference was not statistically significant. Despite the lack of protocol guidelines, RT use did not differ between arms, nor did RT dose, treatment interruption, or completion. CONCLUSION: Despite the delay to RT during additional chemotherapy, adjuvant AC+T afforded better local control than AC alone in patients treated with breast-conserving therapy. Addition of paclitaxel did not adversely affect delivery or ability to tolerate RT, as indicated by similar rates of completion of timely, full-dose RT between arms.