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A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis.

ABSTRACT: Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

SUBMITTER: Yan M

PROVIDER: S-EPMC8229231 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:Various radiation schedules are used in concurrent chemoradiation therapy for limited-stage small cell lung cancer (LS-SCLC). Since there is currently no randomized evidence comparing hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC. METHODS AND MATERIALS:Patients with LS-SCLC treated between 2000 and 2013 with HFRT (40 Gy/15 fractions, 45 Gy/15 fractions, 45 Gy/20 fractions) or CFRT (60 Gy/30 or 66 Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events. RESULTS:In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, more often smoked concurrently with treatment, had higher Eastern Cooperative Oncology Group performance status, different T and N stage patterns, and more commonly received concurrent chemoradiation therapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts, respectively. There was no difference in OS (P = .724), PFS (P = .862), or any pulmonary (P = .350) or esophageal (P = .097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P = .020). Multivariable Cox regression also revealed no differences in OS (P = .886) or PFS (P = .717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed. CONCLUSIONS:In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies.

Project description:Simple Summary The “gold standard” for limited-stage small cell lung cancer (LS-SCLC) is 45 Gy in 1.5 Gy twice-daily fractions (HYPER) thoracic radiotherapy (TRT) scheduled concurrently with platinum-etoposide chemotherapy. However, the HYPER TRT regimen has failed to be universally implemented, mainly due to its inconvenience and notably increased acute esophageal toxicity (Grade ≥3, 19–27%). We successfully innovated the segmental abutting esophagus-sparing (SAES) technique in order to reduce the radiation dose of the esophagus. Based on a cohort derived from a prospective phase III clinical trial, the SAES technique significantly reduced severe acute esophagitis (≥Grade 3: 3.3%) in patients receiving hypofractionated (HYPO) radiotherapy (45 Gy in 3 Gy once-daily fractions) concurrently with chemotherapy. Thus, the SAES technique could help to achieve better tolerance of the HYPO schedule and provide good feasibility for dose escalation, which may translate to better local control and prognosis in the future. Abstract The aim of the current study is to evaluate the effect of segmental abutting esophagus-sparing (SAES) radiotherapy on reducing severe acute esophagitis in patients with limited-stage small-cell lung cancer treated with concurrent chemoradiotherapy. Thirty patients were enrolled from the experimental arm (45 Gy in 3 Gy daily fractions in 3 weeks) of an ongoing phase III trial (NCT 02688036). The whole esophagus was divided into the involved esophagus and the abutting esophagus (AE) according to the distance from the edge of the clinical target volume. All dosimetric parameters were significantly reduced for the whole esophagus and AE. The maximal and mean doses of the esophagus (47.4 ± 1.9 Gy and 13.5 ± 5.8 Gy, respectively) and AE (42.9 ± 2.3 Gy and 8.6 ± 3.6 Gy, respectively) in the SAES plan were significantly lower than those (esophagus 48.0 ± 1.9 Gy and 14.7± 6.1 Gy, AE 45.1 ± 2.4 Gy and 9.8 ± 4.2 Gy, respectively) in the non-SAES plan. With a median follow-up of 12.5 months, only one patient (3.3%) developed grade 3 acute esophagitis, and no grade 4–5 events happened. SAES radiotherapy has significant dosimetric advantages, which are successfully translated into clinical benefits and provide good feasibility for dose escalation to improve local control and prognosis in the future.

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A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis.

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