What is the role of consolidative thoracic radiotherapy in the era of chemo-immunotherapy for extensive stage small cell lung cancer?
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ABSTRACT:
SUBMITTER: Higgins KA
PROVIDER: S-EPMC7656365 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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What is the role of consolidative thoracic radiotherapy in the era of chemo-immunotherapy for extensive stage small cell lung cancer?
Higgins Kristin A KA Slotman Ben J BJ
Journal of thoracic disease 20201001 10
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Project description:Extensive stage small cell lung cancer (ES-SCLC) represents approximately half of all diagnosed small cell lung cancer worldwide. It is notorious for a high risk of local recurrence although it's sensitive to chemotherapy. Nearly 90% of intrathoracic failures happen in the first year after diagnosis. The cornerstone of treatment for ES-SCLC is etoposide-platinum based chemotherapy. Consolidative radiotherapy to thorax has diminished the incidence of local relapse, therefore it should be offered to patients with excellent response to induction first-line chemotherapy. This review centers on the clinical evidence for the use of thoracic radiotherapy (TRT) and current modalities of TRT delivery, then tries to determine a feasible way to conduct TRT in a selective group of cases.
| S-EPMC5400661 | biostudies-literature
Project description:PurposeExtensive-stage small cell lung cancer (ES-SCLC) carries a dismal prognosis. The benefit of consolidative thoracic radiotherapy (TR) after first-line chemoimmunotherapy with PD-L1 inhibitors in this setting remains unclear. As TR can improve overall survival (OS) after conventional chemotherapy, we retrospectively analyzed OS of an inhouse cohort treated either with TR or with chemoimmunotherapy alone.MethodsA total of 41 patients treated with chemoimmunotherapy with PD-L1 inhibitors (atezolizumab or durvalumab) for ES-SCLC at our hospital since 2019 were analyzed. TR was administered in 10 fractions of 3 Gy. Patient characteristics, number of immunotherapy cycles received, brain irradiation, and presence of hepatic and cerebral metastasis at diagnosis were assessed. Primary endpoint was OS after first diagnosis.ResultsConsolidative TR was associated with a significantly longer OS than systemic therapy alone (1-year OS 78.6% and 2‑year OS 37.1% vs. 1‑year OS 39.7% and 2 years not reached, p = 0.019). With regard to radiotherapy indication, survival at 1 year was 88.9% (log-rank p = 0.016) for patients receiving consolidative TR. For patients receiving TR in case of progression, 1‑year survival was 66.7%. Hepatic and cerebral metastasis at first diagnosis had no significant effect on OS.ConclusionTR was significantly associated with longer OS. The survival benefit of TR was most pronounced for consolidative radiotherapy after initial chemoimmunotherapy compared to TR in case of progression. Although retrospective findings need to be interpreted with caution, in the absence of prospective data, our findings provide a basis for offering consolidative TR in the era of chemoimmunotherapy.
| S-EPMC10281891 | biostudies-literature
Project description:The improvement in treatment strategies and outcomes in small cell lung cancer (SCLC) has lagged behind other cancers. The addition of immune checkpoint inhibitors (ICIs), durvalumab and atezolizumab, to the platinum-based chemotherapy in frontline setting has improved the survival in extensive stage SCLC, (ES-SCLC), albeit modestly, and is now the new standard of care. Prior to advent of immunotherapy into the therapeutic armamentarium in ES-SCLC, consolidative thoracic radiotherapy (TRT) was associated with improved thoracic control and survival outcomes. In the era of ICIs, the role of TRT is not well defined, chiefly because TRT was not incorporated in any immunotherapy trials, secondly due to concerns regarding the increased risks of pneumonitis, and finally uncertain magnitude of benefit with this combined approach. In principle, radiation can increase in the immunogenicity of tumor and hence the activity of immune checkpoint blockade, thereby increasing efficacy both locally and distantly. Such an approach has been promising in non-small cell lung cancer with ICIs improving outcomes after concurrent chemoradiation, but remains unanswered in ES-SCLC. It is, thus, possible that the modest improvement in survival by addition of ICIs to chemotherapy in ES-SCLC can be further improved by the incorporation of consolidative TRT in selected patients. Several early phase trials and retrospective studies have suggested that such an approach may be feasible and safe. Prospective trials are ongoing to answer whether adding radiation therapy to chemoimmunotherapy will improve outcomes in ES-SCLC.
| S-EPMC10467203 | biostudies-literature
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.
| S-EPMC10493776 | biostudies-literature
Project description:BackgroundImmunotherapy has greatly increased the survival time of patients with extensive-stage small cell lung cancer (ES-SCLC), and is now a standard first-line treatment for these patients. Increasing evidence suggests a possible synergistic effect between immunotherapy and radiotherapy, yet there is a paucity of evidence regarding the efficacy and safety of thoracic radiotherapy (TRT) combined with chemo-immunotherapy for ES-SCLC.MethodsThe medical records of 78 consecutive patients with ES-SCLC who received TRT in combination with chemo-immunotherapy at Jinling Hospital and Jiangsu Cancer Hospital from January 2019 to January 2023 were retrospectively reviewed. The median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, and the incidence of adverse events (AEs) was used to evaluate safety.ResultsThe median follow-up time was 31.9 months, the objective response rate (ORR) was 59%, and the disease control rate (DCR) was 89.8%. The mOS time was 20.0 months, and the 6-month OS rate was 95%. The mPFS time was 9.2 months, and the 6-month PFS rate was 78%. There were no treatment-related deaths. The incidence of pneumonitis was 23.1%, the incidence of radiation esophagitis was 5.1%, and 2 patients experienced high-grade pneumonitis. Primary liver metastasis was a predictor of poor OS and PFS. Patients who received consolidative TRT after chemo-immunotherapy experienced more benefit than those who received TRT as palliative or salvage treatment for superior vena cava syndrome or disease progression.ConclusionsTRT is a feasible treatment for patients who receive chemo-immunotherapy for the management of ES-SCLC in consideration of its considerable efficacy and tolerable safety risk. This treatment is especially useful for patients without primary liver metastasis and who receive consolidative TRT after chemo-immunotherapy. Large-scale prospective studies are needed to confirm the efficacy and safety of this treatment modality.
| S-EPMC10654438 | biostudies-literature
Project description:BackgroundExtensive-stage small cell lung cancer (ES-SCLC) remains a challenging malignancy with a poor prognosis. The integration of immunochemotherapy and combined consolidative thoracic radiotherapy (cTRT) presents a potential paradigm shift in treatment. This study aims to evaluate the real-world efficacy and safety of this approach.MethodsIn a single-center retrospective study conducted at Shandong Cancer Hospital, electronic medical records of 828 ES-SCLC patients treated between January 1, 2022, and December 31, 2023, were reviewed. Patients were divided into three cohorts based on treatment strategies: chemoradiotherapy (cohort A), immunochemotherapy without/with cTRT (cohort B/C). Propensity score matching was utilized to adjust for baseline differences. The primary outcomes were real-world progression-free survival (rwPFS) and overall survival (OS). Secondary outcomes included the incidence and severity of specific interested adverse events (AEs).ResultsOf the 374 patients analyzed, cohort C showed significant improvements in rwPFS and OS compared to cohort A. The median rwPFS in cohort C (10.9 months) was longer than that of cohorts A (7.6 months) and B (8.0 months). The 12-month rwPFS rate was highest in cohort C (41%), compared to cohorts A (19%) and B (34%). The incidence of grade 3 or higher AEs was comparable across cohorts, with myelosuppression being the most common. However, the incidence of grade 3 or higher pneumonitis was notably higher in cohorts B and C, aligning with previous reports.ConclusionsThe combination of cTRT with immunochemotherapy for ES-SCLC showed improved rwPFS and OS, indicating potential benefit in this population. The overall safety profile remained manageable. These findings highlight the need for further prospective studies to confirm the optimal integration of cTRT in ES-SCLC treatment strategies.
| S-EPMC11898347 | biostudies-literature
Project description:PurposeThis study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment.Materials and methodsWe retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group.ResultsThe median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively).ConclusionIn ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.
| S-EPMC11016648 | biostudies-literature
Project description:Small cell lung cancer has been a difficult disease to treat with poor survival and few significant improvements in outcomes in the last three decades. Most recently the addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) resulted in improved overall survival and progression-free survival compared to chemotherapy alone. Recent randomized studies examining both consolidative thoracic radiotherapy and prophylactic cranial irradiation (PCI) in ES-SCLC have impacted the utilization of these interventions. The approval of immune checkpoint inhibitors (ICIs) to platinum/etoposide chemotherapy for the treatment of ES-SCLC in the front-line setting may also further impact the role of radiotherapy in this disease. In this article, we review the current evidence supporting thoracic radiotherapy in ES-SCLC and discuss the promising therapeutic implications of thoracic radiation in light of the inclusion of ICIs. We also address how the increasing routine use of surveillance brain magnetic resonance imaging (MRI) and ICIs may diminish the use of PCI in ES-SCLC.
| S-EPMC6795575 | biostudies-literature
Project description: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.
| S-EPMC6310308 | biostudies-other
Project description:BackgroundThe role of prophylactic cranial irradiation (PCI) is not well-defined in extensive-stage SCLC (ES-SCLC), with conflicting results from randomized trials and a lack of relevant data for patients who received consolidative thoracic radiotherapy (CTRT). We sought to evaluate the impact of PCI on the outcomes of ES-SCLC patients who were all treated with CTRT.MethodsA retrospective analysis of ES-SCLC patients without brain metastases who were all treated with CTRT between 2013-2021 at our institution was conducted. Overall survival (OS) and incidence of brain failure (BFR) were estimated using Kaplan-Meier estimation and cumulative incidence function. Multivariable Cox or Fine-Gray's proportional hazard regression analysis (MVA) were performed to determine association between PCI and OS.Results47 patients met inclusion criteria and were theoretically eligible for PCI, 27 (57.4 %) received PCI and CTRT while 20 (42.6 %) received CTRT alone. Baseline characteristics were similar except for age, where patients receiving PCI were younger (median age 62) compared to patients who did not receive PCI (median age 72). Median OS with PCI was 19.2 months, compared to 10.8 months without PCI (P = 0.0334). This improved OS remained apparent in patients who received post-chemotherapy MRI restaging (P = 0.0245). BFR was reduced with PCI (HR = 0.22 [0.09-0.52], P = 0.0004). On MVA, PCI was significantly and independently associated with improved OS (HR = 0.39 [0.19-0.80], P = 0.01) and reduced BFR (HR = 0.20 [0.09-0.44], P = < 0.001).ConclusionThis real-world study found PCI was independently associated with improved OS and reduced BFR in ES-SCLC patients treated with CTRT compared to patients treated with CTRT not receiving PCI, including after post-chemotherapy brain MRI. The role of PCI with CTRT should be evaluated in prospective studies.
| S-EPMC11787411 | biostudies-literature