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Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer.

ABSTRACT: Treatment of extensive-stage small-cell lung cancer remains a challenge with poor local control and overall survival. Chemotherapy is the mainstay of treatment, consisting of a combination of a platinum agent plus etoposide. The role of consolidative chest radiotherapy in extensive-stage small-cell lung cancer remains controversial. Two randomized clinical trials have been published demonstrating improved intrathoracic disease control with a small survival benefit, though interpretation and application of these results to clinical practice has been debated. These two trials examined different radiotherapy techniques and doses, with a third trial treating consolidative chest and oligometastatic disease having closed prematurely due to an interim analysis demonstrating treatment futility plus increased toxicity. Patients with residual intrathoracic disease after chemotherapy appear to benefit the most from consolidative chest radiotherapy, offering a potential tool to help select appropriate patients.

SUBMITTER: Corkum MT

PROVIDER: S-EPMC6310308 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer.

Corkum Mark T MT Rodrigues George B GB

Lung cancer management 20171117 2

Treatment of extensive-stage small-cell lung cancer remains a challenge with poor local control and overall survival. Chemotherapy is the mainstay of treatment, consisting of a combination of a platinum agent plus etoposide. The role of consolidative chest radiotherapy in extensive-stage small-cell lung cancer remains controversial. Two randomized clinical trials have been published demonstrating improved intrathoracic disease control with a small survival benefit, though interpretation and appl ...[more]

PMID: 30643570

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Project description:ObjectiveThe purpose of this study was to assess whether thoracic radiotherapy (TRT) combined with chemotherapy (CHT) showed promising anti-tumour activity in extensive-stage small cell lung cancer (ES-SCLC), to explore practice patterns for the radiation time and dose/fractionation and to identify prognostic factors for patients who would benefit from CHT/TRT.MethodsA total of 492 ES-SCLC patients were included from January 2010 to March 2019, 244 of whom received CHT/TRT. Propensity score matching was performed to minimize bias between the CHT/TRT and CHT-alone groups. Patients in the CHT/TRT group were categorized into four subgroups based on the number of induction CHT cycles. For effective dose fractionation calculations, we introduced the time-adjusted biological effective dose (tBED). Categorical variables were analysed with chi-square tests and Fisher's exact tests. Kaplan-Meier curves were generated to estimate survival rates using the R-project. Multivariate prognostic analysis was performed with Cox proportional hazards models.ResultsPatients who received CHT/TRT experienced improved overall survival (OS) (18.1 vs 10.8 months), progression-free survival (PFS) (9.3 vs 6.0 months) and local recurrence-free survival (LRFS) (12.0 vs 6.6 months) before matching, with similar results after matching. In the CHT/TRT group, the median LRFS times for the groups based on the radiation time were 12.7, 12.0, 12.0, and 9.0 months, respectively. Early TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.0 vs 7.7 months, respectively, p = 0.091) but not OS (median 17.6 vs 19.5 vs 17.2 vs 19.0 months, respectively, p = 0.622). Notably, patients who received TRT within 6 cycles of CHT experienced prolonged LRFS (p = 0.001). Regarding the radiation dose, patients in the high-dose group (tBED > 50 Gy) who achieved complete response and partial response (CR and PR) to systemic therapy had relatively short OS (median 27.1 vs 22.7, p = 0.026) and PFS (median 11.4 vs 11.2, p = 0.032), but the abovementioned results were not obtained after the exclusion of patients who received hyperfractionated radiotherapy (all p > 0.05).ConclusionCHT/TRT could improve survival for ES-SCLC patients. TRT performed within 6 cycles of CHT and hyperfractionated radiotherapy (45 Gy in 30 fractions) may be a feasible treatment scheme for ES-SCLC patients.

Project description:Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Dataset Information

Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer.

Publications

Patient selection for thoracic radiotherapy in extensive-stage small-cell lung cancer.

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