Robert MacRae

Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non–Small-Cell Lung Cancer

PURPOSE To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Eligible patients with <5% weight loss and good performance status received two cycles of pemetrexed (300, 400, or 500 mg/m(2) on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m(2) Days 1-3 for Dose Levels 1-3; 20 mg/m(2) Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m(2), 75 mg/m(2)) 21 days apart, after concurrent therapy. RESULTS Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. CONCLUSIONS Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

Pretreatment [18F]-fluoro-2-deoxy-glucose Positron Emission Tomography Maximum Standardized Uptake Value as Predictor of Distant Metastasis in Early-Stage Non-Small Cell Lung Cancer Treated With Definitive Radiation Therapy: Rethinking the Role of Positron Emission Tomography in Personalizing Treatment Based on Risk Status

PURPOSE The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. RESULTS The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. CONCLUSION In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

Association between Anemia Arising during Therapy and Outcomes of Chemoradiation for Limited Small-cell Lung Cancer

Background: Anemia during chemoradiation is associated with poorer outcomes in various cancers. Concurrent chemoradiation (CCRT) is standard therapy for fit patients with limited small-cell lung cancer (LD-SCLC). The objective of this study was to explore the relationship between anemia and treatment outcomes in patients with LD-SCLC treated with CCRT. Methods: Charts of all patients with LD-SCLC receiving CCRT at The Ottawa Hospital Regional Cancer Centre between January 1996 and December 2002 were reviewed. Information extracted included demographics, known prognostic factors, treatment details, and hemoglobin values from diagnosis until the completion of therapy. Factors associated with outcomes were determined by Cox regression analyses. Results: One hundred thirty patients were eligible for inclusion, and their median survival was 18.1 months (95% CI, 14.8–25.1 months). By univariate analysis, poorer outcome was associated with Eastern Cooperative Oncology Group performance status ≥2, supraclavicular adenopathy, and pre-radiotherapy hemoglobin <100 g/liter. Pre-radiotherapy hemoglobin <100 g/liter was associated with both an increased risk of progression (hazard ratio 1.8; P = 0.04) and death (hazard ratio 1.9; P = 0.02) by multivariate analysis. Conclusion: Anemia during CCRT for LD-SCLC is common and may be associated with poorer outcome. Whether this association is causative or simply prognostic is unclear, and it is not known whether correction or prevention of anemia will improve outcome. Clinical trials evaluating different target hemoglobin levels and the roles of transfusion or erythropoietin during CCRT are needed.

Quantitative texture analysis on pre-treatment computed tomography predicts local recurrence in stage I non-small cell lung cancer following stereotactic radiation therapy

Background The prediction of local recurrence (LR) of stage I non-small cell lung cancer (NSCLC) after definitive stereotactic body radiotherapy (SBRT) remains elusive. The purpose of this study was to assess whether quantitative imaging features on pre-treatment computed tomography (CT) can predict LR beyond 18 (18F) fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT maximum standard uptake value (SUVmax). Methods This retrospective study evaluated 36 patients with 37 stage I NSCLC who had local tumor control (LC; n=19) and (LR; n=18). Textural features were extracted on pre-treatment CT. Mann-Whitney U tests were used to compare LC and LR groups. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) calculated with LR as outcome. Results Gray-level correlation and sum variance were greater in the LR group, compared with the LC group (P=0.02 and P=0.04, respectively). Gray-level difference variance was lower in the LR group (P=0.004). The logistic regression model generated using gray-level correlation and difference variance features resulted in AUC (SE) 0.77 (0.08) (P=0.0007). The addition of 18F-FDG PET/CT SUVmax did not improve the AUC (P=0.75). Conclusions CT textural features were found to be predictors of LR of early stage NSCLC on baseline CT prior to SBRT.

Phase II Study of Concurrent Pemetrexed, Cisplatin, and Radiation Therapy for Stage IIIA/B Unresectable Non–Small Cell Lung Cancer

INTRODUCTION Concurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non-small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established. PATIENTS AND METHODS In the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m(2) intravenously on days 1 and 22, 20 mg/m(2) intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg(2)) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1-year OS rate was ≥ 70%. RESULTS A total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively. CONCLUSION Full-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation.

Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic ablative radiotherapy for medically inoperable stage I non-small cell lung cancer

Purpose In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). Methods Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50–60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0–1, 2–3, 4–9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. Results The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7–12 had an increased hazard of death on univariate analysis HR 2.45 (1.15–5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04–4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30–2.90) but not on multivariate analysis. On formalized testing – with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. Conclusion We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

236: Validity of Specific Growth Rate in Stage I Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy (SBRT)

CARO 2016 _________________________________________________________________________________________________________ concentration of the metabolite in the cancer group (p = 0.040). Subsequently, EBC samples were analyzed by an LC-QTOF-Mass Spectroscopy (MS) using a non-targeted approach. A total of 625 compounds were detected in all EBC samples combined among which, four were up regulated in patients with lung cancer (TTest, p < 0.05). Conclusions: Lower concentrations of methanol (EBC), glycoprotein (sputum), absence of glucose in sputum identified through MRS and up regulation of four specific metabolites in EBC identified through MS in patients with known lung cancer suggest that MRS and MS may provide a lung cancer specific metabolic profile that can be used to develop a non-invasive tool to screen for lung cancer in high-risk population.