Predictors of pulmonary toxicity in limited-stage (LS) small cell lung cancer (SCLC) patients treated with concurrent chemotherapy (CTX) and high-dose (70 Gy) daily radiotherapy (RT): a pooled analysis of three CALGB studies

General Poster Session: Lung Cancer - Local-regional and Adjuvant Therapy/Small Cell: abstract no. 7078This journal suppl. entitled: ASCO Meeting Abstracts Part 1BACKGROUND: Predictors of post CTX-RT pulmonary toxicity in LS-SCLC patients are not well defined. Current guidelines are derived from NSCLC regimens, not accounting for the unique biology of SCLC. We analyzed patients on 3 consecutive CALGB LS-SCLC trials to determine factors predicting for post-treatment pulmonary toxicity. METHODS: Patients treated on CALGB protocols 39808, 30002, 30206, investigating 2 cycles of newer CTX agents (39808: topotecan, paclitaxel; 30002: paclitaxel, oral etopside, oral topotecan; 30206: cisplatin, irinotecan) followed by concurrent carboplatin/etopside and 70 Gy daily RT were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3-5 pulmonary toxicities following CTX-RT. PFT data were not routinely collected and not included in this analysis. RESULTS: 211 patients were treated, 100 patients (39808 n=9, 30002 n=34, 30206 n=57) were evaluable with RT dose-volume parameters and adverse event data. Patient characteristics were balanced between except for those in 30206 with significantly improved baseline PS. Median overall and progression free survival was 22.6 months (95% CI: 18.5-29.4) and 13.9 months (95% CI: 12.6-16.7), respectively. Three patients experienced post-treatment pulmonary toxicity. No patients experienced grade 4-5 pulmonary toxicity. Patients with post-treatment grade 3 pulmonary toxicity were likely to be older (p=0.09) and have a smaller total lung volume (p=0.05). Furthermore, exposure of larger volumes of lung to lower (median V5=70%, p=0.09, median V10=63%, p=0.07), intermediate (median V20=50%, p=0.04) and high (median V60=25%, p=0.01) doses of RT were all associated with grade 3 pulmonary toxicity, as was larger mean lung RT dose (median 31 Gy p=0.02). CONCLUSIONS: Post-treatment pulmonary toxicity following completion of 2 cycles CTX followed by CTX-RT was uncommon. Few events limtied statistical power to draw firm conclusions. Data available suggest that care should be taken to minimize mean lung RT exposure, as well as volumes of low, intermediate and high doses of RT

Positive Interaction between Prophylactic Cranial Irradiation and Maintenance Sunitinib for Untreated Extensive-Stage Small Cell Lung Cancer Patients After Standard Chemotherapy: A Secondary Analysis of CALGB 30504 (ALLIANCE)

BACKGROUND: Prophylactic cranial irradiation (PCI) has become a standard option for patients with extensive-stage small cell lung cancer (ES-SCLC). The Cancer and Leukemia Group B 30504 trial was a randomized phase II study of the effect of sunitinib versus placebo in ES-SCLC patients responding to platinum-based systemic therapy. The study required preenrollment brain imaging. PCI was provided at the discretion of treating physicians. We performed a secondary analysis of the Cancer and Leukemia Group B trial to determine the impact of PCI on patients with ES-SCLC. METHODS: Fisher's exact test and the Wilcoxon rank-sum test were conducted to identify the differences between patients receiving PCI and patients not receiving PCI. Kaplan-Meier analyses described progression-free survival (PFS) and overall survival (OS) for patients in the PCI and non-PCI groups. RESULTS: A total of 85 patients received maintenance therapy (41 received placebo and 44 received sunitinib). Patient characteristics were balanced between the PCI and non-PCI groups. The patients receiving PCI plus sunitinib had a nonsignificant 2.7-month improvement in PFS (5.0 months versus 2.3 months, p = 0.14, hazard risk [HR] = 0.62, 95% confidence interval [CI]: 0.33-1.18) trending toward improved OS (8.9 months versus 5.4 months, p = 0.053, HR = 0.47, 95% CI: 0.22-1.03). PCI was associated with a trend toward improved median PFS (2.9 months versus 2.2 months, p = 0.096, HR = 0.69, 95% CI: 0.45-1.07) but not median OS (8.3 months in the PCI group versus 8.7 months in the non-PCI group, p = 0.76, HR = 1.07, 95% CI: 0.67-1.71). The patients receiving placebo had no improvement in PFS or OS with PCI. CONCLUSIONS: Trends toward improved PFS and OS were seen in patients receiving PCI and sunitinib, thus supporting the need for further prospective research evaluating the integration of maintenance systemic therapy and PCI for patients with ES-SCLC. Improved outcomes for patients with ES-SCLC after induction chemotherapy may require PCI, thoracic radiotherapy, and maintenance systemic therapy to achieve control of both intracranial and extracranial disease.link_to_subscribed_fulltex