Accelerated Hyperfractionated Radiation Therapy Within Trimodality Therapy Concepts For Stage Iiia/B Non-Small Cell Lung Cancer: Markedly Higher Rate Of Pathologic Complete Remissions Than With Conventionally Fractionated Radiochemotherapy

Purpose/Objective(s)Pathologic complete remission (pCR) after neoadjuvant radiochemotherapy (RTx/CTx) is related to long-term survival for stage III non-small cell lung cancer (NSCLC) patients and is a surrogate marker for local effectiveness. Repopulation is a problem for fast growing tumors and accelerated-hyperfractionation (AHF) has been proven to be superior in SCLC. For NSCLC, data are missing up to now that demonstrate progress over conventionally fractionated (CF) RTx/CTx to lead a way for further treatment optimization.Materials/MethodsWe retrospectively reviewed all consecutive patients treated at our institution with neoadjuvant RTx/CTx and curative resection between August 2000 and December 2011. Patients received induction chemotherapy (cisplatin/etoposide, cisplatin/taxol) followed by a) AHF-RTx (45 Gy/1.5 Gy bid, with concurrent cisplatin/etoposide, cisplatin/vinorelbine) or b) CF-RTx (46 Gy/2 Gy qd, with concurrent cisplatin/etoposide, cisplatin/vinorelbine). Patients were offered AHF-RTx only within prospective trials during this time interval. During periods of no open trial or in patients who did not meet protocol inclusion criteria (i.e., previous cancer, patient's preference), CF-RTx was applied.ResultsOne hundred fifty-five patients, m/f:96/59, median age 58 years (range, 34-78 years), stage IIIA/B:69/86, squamous cell/adeno/large cell carcinoma:79/60/15, G1/2/3:2/57/86, were analyzed; 81 patients received AHF-RTx, 74 patients CF-RTx. For both groups, no differences in patient and tumor related factors as age, gender, LDH, hemoglobin, T-stage, N-stage, histopathology, grading, and distribution of the start of treatments were found (p > 0.1). However, median times from start of radiation therapy until resection were significantly longer for CF (72 d) in comparison to AHF (54 d). Using univariate analysis, AHF was associated with a significantly higher pCR rate than CF (40% vs. 22%, p = 0.017, relative chance to achieve pCR: 1.83 (95% CI: 1.1-3.05). Adenocarcinomas had a significantly lower pCR-rate in comparison to the other histologies, equally as cN3 patients who had a worse pCR-rate than the other patients. Using multivariate logistic regression with backward elimination of all aforementioned factors, only AHF (p = 0.017), adenocarcinoma (p = 0.03), and cN3 (p = 0.02) remained independently significant. Long-term survival of patients with pCR was above 50%.ConclusionsThis large monoinstitutional study demonstrates a substantial advantage of AHF in comparison to CF on downstaging of lung cancer despite the longer time given for tumor regression until resection by the CF schedule. Purpose/Objective(s)Pathologic complete remission (pCR) after neoadjuvant radiochemotherapy (RTx/CTx) is related to long-term survival for stage III non-small cell lung cancer (NSCLC) patients and is a surrogate marker for local effectiveness. Repopulation is a problem for fast growing tumors and accelerated-hyperfractionation (AHF) has been proven to be superior in SCLC. For NSCLC, data are missing up to now that demonstrate progress over conventionally fractionated (CF) RTx/CTx to lead a way for further treatment optimization. Pathologic complete remission (pCR) after neoadjuvant radiochemotherapy (RTx/CTx) is related to long-term survival for stage III non-small cell lung cancer (NSCLC) patients and is a surrogate marker for local effectiveness. Repopulation is a problem for fast growing tumors and accelerated-hyperfractionation (AHF) has been proven to be superior in SCLC. For NSCLC, data are missing up to now that demonstrate progress over conventionally fractionated (CF) RTx/CTx to lead a way for further treatment optimization. Materials/MethodsWe retrospectively reviewed all consecutive patients treated at our institution with neoadjuvant RTx/CTx and curative resection between August 2000 and December 2011. Patients received induction chemotherapy (cisplatin/etoposide, cisplatin/taxol) followed by a) AHF-RTx (45 Gy/1.5 Gy bid, with concurrent cisplatin/etoposide, cisplatin/vinorelbine) or b) CF-RTx (46 Gy/2 Gy qd, with concurrent cisplatin/etoposide, cisplatin/vinorelbine). Patients were offered AHF-RTx only within prospective trials during this time interval. During periods of no open trial or in patients who did not meet protocol inclusion criteria (i.e., previous cancer, patient's preference), CF-RTx was applied. We retrospectively reviewed all consecutive patients treated at our institution with neoadjuvant RTx/CTx and curative resection between August 2000 and December 2011. Patients received induction chemotherapy (cisplatin/etoposide, cisplatin/taxol) followed by a) AHF-RTx (45 Gy/1.5 Gy bid, with concurrent cisplatin/etoposide, cisplatin/vinorelbine) or b) CF-RTx (46 Gy/2 Gy qd, with concurrent cisplatin/etoposide, cisplatin/vinorelbine). Patients were offered AHF-RTx only within prospective trials during this time interval. During periods of no open trial or in patients who did not meet protocol inclusion criteria (i.e., previous cancer, patient's preference), CF-RTx was applied. ResultsOne hundred fifty-five patients, m/f:96/59, median age 58 years (range, 34-78 years), stage IIIA/B:69/86, squamous cell/adeno/large cell carcinoma:79/60/15, G1/2/3:2/57/86, were analyzed; 81 patients received AHF-RTx, 74 patients CF-RTx. For both groups, no differences in patient and tumor related factors as age, gender, LDH, hemoglobin, T-stage, N-stage, histopathology, grading, and distribution of the start of treatments were found (p > 0.1). However, median times from start of radiation therapy until resection were significantly longer for CF (72 d) in comparison to AHF (54 d). Using univariate analysis, AHF was associated with a significantly higher pCR rate than CF (40% vs. 22%, p = 0.017, relative chance to achieve pCR: 1.83 (95% CI: 1.1-3.05). Adenocarcinomas had a significantly lower pCR-rate in comparison to the other histologies, equally as cN3 patients who had a worse pCR-rate than the other patients. Using multivariate logistic regression with backward elimination of all aforementioned factors, only AHF (p = 0.017), adenocarcinoma (p = 0.03), and cN3 (p = 0.02) remained independently significant. Long-term survival of patients with pCR was above 50%. One hundred fifty-five patients, m/f:96/59, median age 58 years (range, 34-78 years), stage IIIA/B:69/86, squamous cell/adeno/large cell carcinoma:79/60/15, G1/2/3:2/57/86, were analyzed; 81 patients received AHF-RTx, 74 patients CF-RTx. For both groups, no differences in patient and tumor related factors as age, gender, LDH, hemoglobin, T-stage, N-stage, histopathology, grading, and distribution of the start of treatments were found (p > 0.1). However, median times from start of radiation therapy until resection were significantly longer for CF (72 d) in comparison to AHF (54 d). Using univariate analysis, AHF was associated with a significantly higher pCR rate than CF (40% vs. 22%, p = 0.017, relative chance to achieve pCR: 1.83 (95% CI: 1.1-3.05). Adenocarcinomas had a significantly lower pCR-rate in comparison to the other histologies, equally as cN3 patients who had a worse pCR-rate than the other patients. Using multivariate logistic regression with backward elimination of all aforementioned factors, only AHF (p = 0.017), adenocarcinoma (p = 0.03), and cN3 (p = 0.02) remained independently significant. Long-term survival of patients with pCR was above 50%. ConclusionsThis large monoinstitutional study demonstrates a substantial advantage of AHF in comparison to CF on downstaging of lung cancer despite the longer time given for tumor regression until resection by the CF schedule. This large monoinstitutional study demonstrates a substantial advantage of AHF in comparison to CF on downstaging of lung cancer despite the longer time given for tumor regression until resection by the CF schedule.