Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer

Abstract

Purpose: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy.Materials and Methods: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25–2.28 Gy each administered in 6 weeks up to a total dose of 67.5–68.4 Gy (range, 64.5–71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation.Results: With a median follow up of 27 months (range 6–40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity.Conclusion: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time.

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

“…The addition of cetuximab to carboplatin plus paclitaxel was associated with a significant increase in grade !3 toxicity (86% vs 70%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11% in our study, comparable to the standard-dose treatment arm of the RTOG 0617, whereas our radiation dose of 66 Gy in 24 a/b Z 3) is comparable to the high-dose treatment arm (74 Gy) of the RTOG 0617 study. In the RTOG 0617 study an exclusion criterion was evidence of N3 disease: supraclavicular or contralateral hilar adenopathy.…”

“…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.…”

Radiation dose escalation with modified fractionation schedules for locally advanced NSCLC: A systematic review

“…A total of 16 studies used cCRT (table). In six of these, one treatment arm was either sCRT or RT alone. A total of 18 applied nonconcomitant treatment, ie, sCRT or RT alone (Table ).…”

“…Dose escalation by modified fractionation as the primary strategy to increase LC has been explored in several phase I and II studies . In 2015 the RTOG 0617 trial, which applied conventional dose escalation, was negative for the experimental arm in terms of LC and OS .…”

Strategies of Dose Escalation in the Treatment of Locally Advanced Non-Small Cell Lung Cancer: Image Guidance and Beyond

“…This is especially true for chemo-radiation delivered with IGRT (74–78). As shown in Table 2, excellent median survival and local control have been frequently observed when hypofractionated, image-guided IMRT was delivered with concurrent chemotherapy.…”