Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

Abstract

BACKGROUND:The objective of the current study was to evaluate the feasibility and toxicity of radiation dose escalation with concurrent chemotherapy using helical tomotherapy (HT) in patients with inoperable, locally advanced, stage III nonsmall cell lung cancer (LANSCLC) (grading determined according to the American Joint Committee on Cancer 6th edition grading system).METHODS:This phase 1/2 study was designed to determine the maximum tolerated dose (MTD) of radiotherapy in patients with LANSCLC administered concurrently with docetaxel and cisplatin. Radiotherapy was delivered using HT. A dose per fraction escalation was applied starting at 2 grays (Gy), with an increase of 6% per dose cohort (DC). The Radiation Therapy Oncology Group acute radiation morbidity score was used to monitor pulmonary, esophageal, and cardiac toxicity.RESULTS:Dose escalation was performed in 34 patients over 5 DCs to a dose per fraction of 2.48 Gy. No differences were observed in acute toxicity between the different DCs. However, a significant increase in late lung toxicity in DC IV, which received a fraction size of 2.36 Gy, necessitated a halt in further dose escalation with the MTD defined as 2.24 Gy per fraction. The overall incidence of acute grade ≥3 esophageal and pulmonary toxicity was 24% and 3%, respectively (grading determined according to the Radiation Therapy Oncology Group‐European Organisation for Research and Treatment of Cancer toxicity scoring system). The overall incidence of late lung toxicity was 21%, but the incidence was an acceptable 13% in DCs I, II, and III. The local response rate was 61% on computed tomography images.CONCLUSIONS:The use of HT to 67.2 Gy with concurrent cisplatin/docetaxel was feasible and resulted in acceptable toxicity. A full phase 2 study has been initiated to establish the true local response rate at the MTD of 2.24 Gy per fraction. Cancer 2010. © 2010 American Cancer Society.

Concurrent Daily Cisplatin and High-Dose Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer

“…In 2015 Kaster et al published a systematic review of radical-intent hypofractionated radiation therapy for locally advanced NSCLC (22)(23)(24). They found a moderate linear relationship between biological effective dose and overall survival and greater acute esophageal toxicity with concurrent chemotherapy.…”

Concurrent chemoradiotherapy with tomotherapy in locally advanced non-small cell lung cancer: a phase i, docetaxel dose-escalation study, with hypofractionated radiation regimen

“…To our knowledge this is the first study of Tomotherapy with weekly concurrent chemotherapy in a dose escalation study of Docetaxel, in the treatment of NSCLC. There was a previous published study of Tomotherapy and concurrent chemotherapy, with fixed dose of chemotherapy, Cisplatin and Docetaxel at a dose of 20 mg/m 2 /weekly, each administered weekly and with radiotherapy fraction size escalation [29]. Although it was not a primary endopoint for this study, the PFS and OS of the patients recruited in the study are encouraging, well above the median data obtained in the previous studies with chemo-radiation for locally advanced NSCLC; however they need further validation through phase II, multi-institutional studies and eventually comparative phase III trials.…”

Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc

“…The arc lengths were set in order to avoid entrance from the contra-lateral lung (depending on target location and extension), and to avoid the posterior entrances, where the couch bars were positioned. For further details on the RapidArc technique see references [15,16]. …”

“…Both Helical Tomotherapy, and to a lesser extent conventional three-dimensional conformal radiotherapy, have shown the potential to significantly decrease radiation dose to lung and other normal structures in the treatment of NSCLC, providing important implications, in terms of acceptable acute toxicities recorded, for dose escalation strategies in the future[15,16]. In a report of volumetric changes, measured in the primary tumor on megavoltage-computed tomography (MVCT) during chemoradiation, Helical Tomotherapy showed also to be effective in reduce tumour volume in NSCLC[17].…”