Abstract

PurposeNot all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification.Methods and MaterialsIsotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues).ResultsThirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1).ConclusionsIsotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

Highlights

  • The current 5-year survival of stage III non-small cell lung cancer (NSCLC) with standard treatment is approximately 20% to 30% at best,[1,2,3] highlighting the urgency to improve outcomes

  • Concurrent chemoradiotherapy, chemotherapy, and radiation therapy (RT) given at the same time is the standard of care in stage III NSCLC followed by durvalumab in patients who are fit and have responded to treatment.[4]

  • Because of small numbers, it is not appropriate to compare the results of isotoxic intensity modulated radiation therapy (IMRT) to large contemporary data sets of patients treated with concurrent CRT, such as RTOG0617 and PACIFIC.[4,12]

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Summary

Introduction

The current 5-year survival of stage III non-small cell lung cancer (NSCLC) with standard treatment is approximately 20% to 30% at best,[1,2,3] highlighting the urgency to improve outcomes. Concurrent chemoradiotherapy (cCRT), chemotherapy, and radiation therapy (RT) given at the same time is the standard of care in stage III NSCLC followed by durvalumab in patients who are fit and have responded to treatment.[4] for most patients, this treatment is unsuitable because of comorbidities and poor performance status (PS).[5] A national audit of the management and outcomes of stage III NSCLC conducted in England in 2016 showed that only 17% of stage III patients were treated with curative-intent RT. Local control with standard 3-dimensional conformal RT (3D-CRT) alone remains poor, with reported 2-year locoregional control rates of 20% to 44%.1,7,8 meta-analysis data has shown that improved local control in lung cancer can lead to improvement in survival.[1]

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