Dataset Information

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up.

ABSTRACT:

Background

Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC.

Methods

Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. The prescribed doses were 30 Gy/5 daily fractions at the reference isodose (60-70%) to the tumor, and 25 Gy/5 daily fractions to the clinically involved lymph nodes. The primary end-point was response rate (RR); the secondary end-points were acute and late side-effects, local progression-free survival (PFS), metastasis-free survival (MFS) and overall survival (OS). This trial closed before the first planned interim analysis due to poor accrual.

Results

From January 2009 to January 2012, 17 of the 23 enrolled patients were evaluable. Treatment yielded an overall RR of 82%. Median follow-up was 87 months (range: 6-87), local PFS was 19.8 months (95% CI 9.7 - not reached), MFS was 9.7 months (95% CI 5.8-46.0) and OS was 23 months (95% CI 8.4-48.4). 70% of patients experienced acute G4 neutropenia, 24% G4 leukopenia, 24% G3 paresthesia, 4% G3 cardiac arrythmia, 4% underwent death after chemotherapy. Late toxicity was represented by 24% dyspnea G3.

Conclusions

AHR combined with chemotherapy is feasible with no severe side-effects, and it appears highly acceptable by patients.

Trial registration

This study is registered with the EudractCT registration 2008-006525-14 . Registered on 9 December 2008.

SUBMITTER: Parisi E

PROVIDER: S-EPMC6591967 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up.

Parisi Elisabetta E Genestreti Giovenzio G Sarnelli Anna A Ghigi Giulia G Arpa Donatella D Burgio Marco Angelo MA Gavelli Giampaolo G Rossi Alice A Scarpi Emanuela E Monti Manuela M Tesei Anna A Polico Rolando R Romeo Antonino A

Radiation oncology (London, England) 20190624 1

<h4>Background</h4>Concurrent chemotherapy and radiation using conventional fractionation is the standard treatment for inoperable, locally advanced non-small-cell lung cancer (NSCLC). We tested accelerated hypofractionated radiotherapy (AHR) and chemotherapy for the treatment of locally advanced NSCLC.<h4>Methods</h4>Eligible patients with locally advanced NSCLC were treated with induction chemotherapy (cisplatin and docetaxel), followed by AHR using tomotherapy and consolidation chemotherapy. ...[more]

PMID: 31234868

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Project description:PurposeTo assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer.Materials and methodsA total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves.ResultsThe mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively.ConclusionWith this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

Project description:ImportanceIntrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non-small cell lung cancer (NSCLC).ObjectiveTo determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost.Design, setting, and participantsThis was an early-phase, single-institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II (inoperable/patient refusal of surgery) or III NSCLC (American Joint Committee on Cancer Staging Manual, seventh edition). Patients were enrolled and treated from May 2011 to May 2018, with a median patient follow-up of 18.2 months. Patients advanced to a higher SABR boost dose if dose-limiting toxic effects (any grade 3 or higher pulmonary, gastrointestinal, or cardiac toxic effects, or any nonhematologic grade 4 or higher toxic effects) occurred in fewer than 33% of the boost cohort within 90 days of follow-up. The current analyses were conducted from January to September 2023.InterventionAll patients first received 4 Gy × 10 fractions followed by an adaptive SABR boost to residual metabolically active disease, consisting of an additional 25 Gy (low, 5 Gy × 5 fractions), 30 Gy (intermediate, 6 Gy × 5 fractions), or 35 Gy (high, 7 Gy × 5 fractions) with concurrent weekly carboplatin/paclitaxel.Main outcome and measureThe primary outcome was to determine the MTD.ResultsData from 28 patients (median [range] age, 70 [51-88] years; 16 [57%] male; 24 [86%] with stage III disease) enrolled across the low- (n = 10), intermediate- (n = 9), and high- (n = 9) dose cohorts were evaluated. The protocol-specified MTD was not exceeded. The incidences of nonhematologic acute and late (>90 days) grade 3 or higher toxic effects were 11% and 7%, respectively. No grade 3 toxic effects were observed in the intermediate-dose boost cohort. Two deaths occurred in the high-dose cohort. Two-year local control was 74.1%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. Two-year overall survival was 30.0%, 76.2%, and 55.6% for the low-, intermediate-, and high-dose cohorts, respectively.Conclusions and relevanceThis early-phase, dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is a safe and effective regimen for patients with locally advanced, unresectable NSCLC.Trial registrationClinicalTrials.gov Identifier: NCT01345851.

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Dataset Information

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up.

Background

Methods

Results

Conclusions

Trial registration

Publications

Accelerated hypofractionated radiotherapy plus chemotherapy for inoperable locally advanced non-small-cell lung cancer: final results of a prospective phase-II trial with a long-term follow-up.

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