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

Abstract

Concomitant chemo-radiotherapy (cCRT) with 60 Gy in 30 fractions is the standard of care for stage 111 non-small cell lung cancer (NSCLC). With a median overall survival of 28.7 months at best and maximum locoregional control rates of 70% at two years, the prognosis for these patients is still dismal. This systematic review summarizes data on dose escalation by alternative fractionation, which has been explored as a primary strategy to improve both local control and overall survival over the past three decades. A Pubmed literature search was performed according to the PRISMA guidelines. Because of the large variety of radiation regimens total doses were converted to EQD 2,T . Only studies using an EQD 2,T of at least 49.5 Gy, which corresponds to the conventional 60 Gy in six weeks, were included. In a total of 3256 patients, the median OS was 17 months (range 7.4-30 months). While OS was better for patients treated after the year 2000 (P = 0.003) or with a mandatory 18 F-FDG-PET-CT in the diagnostic workup (P = 0.001), treatment sequence did not make a difference (P = 0.106). The most commonly reported toxicity was acute esophagitis (AE) with a median rate of 24% (range 0%-84%). AE increased at a rate of 0.5% per Gy increment in EQD 2,T (P = 0.016). Dose escalation above the conventional 60 Gy using modified radiation fractionation schedules and shortened OTT yield similar mOS and LRC regardless of treatment sequence with a significant EQD 2,T dependent increase in AE. Key pointsSignificant findings • Modified radiation dose escalation sequentially combined with chemotherapy yields similar outcome as concomitant treatment. • OS is better with the mandatory inclusion of FDG-PET-CT in the diagnostic work-up. • The risk of acute esophagitis increases with higher EQD 2,T . What this study adds • Chemo-radiotherapy (CRT) with modified dose escalation regimens yields OS and LC rates in the range of standard therapy regardless of treatment sequence. This broadens the database of curative options in patients who are not eligible concomitant CRT.

Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline

“…101 Recent SRs and MAs of randomized trials assessing radiation doses have been reported and demonstrate that common doses delivered for locally advanced NSCLC include 64 Gy and 66 Gy in 2 Gy fractions, with 1.8 Gy daily fractions to total 64.8 Gy or 66.6 Gy also used. 23,24 Furthermore, the ongoing phase III NRG Oncology RTOG 1308 trial uses 70 Gy in 2 Gy daily fractions as its standard dose. 183 Comparisons of 60 Gy in 2 Gy fractions with doses above 60 Gy but , 74 Gy specifically delivered in once-daily radiotherapy using 1.8-2.0 Gy fractions are lacking to date.…”

Role and Mechanism of Exosome-Derived Long Noncoding RNA HOTAIR in Lung Cancer

“…Second, when confirmed, most patients were in the late lung cancer stage. According to statistical data, a 5 year survival rate of patients with lung cancer is only close to 15.9%. − Based on this, it is both urgent and challenging for researchers to seek potential molecular diagnostic biomarkers that are reliable and valuable.…”

Feasibility of Stereotactic Body Radiation Therapy on Unresectable Stage III NSCLC with Peripheral Primary Tumor: A Prospective Study (GFPC 01-14)

“…The authors concluded that improving outcomes in stage III NSCLC may involve some form of hypofractionation in the context of systemic concurrent therapy. Studies of radiation dose escalation with modified fractionation schedules in this setting for locally advanced NSCLC were recently analyzed by Zehentmayr et al [18]. In this analysis, dose escalation above the conventional 60 Gy using modified radiation fractionation schedules and shortened overall treatment time yielded similar OS and local regional control regardless of treatment sequence.…”