Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer

doi:10.1016/j.radonc.2011.08.042

Radiotherapy and Oncology

Volume 102, Issue 2, February 2012, Pages 234-238

https://doi.org/10.1016/j.radonc.2011.08.042 Get rights and content

Abstract

Background and purpose

To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT).

Materials and methods

Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25 Gy/10 fractions) and chest RT (40 Gy/15 fractions) were given simultaneously 4–8 weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival.

Results

Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3 months, respectively (median follow-up = 21.8 months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic.

Conclusions

Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.

Section snippets

Eligibility

Accrual to the protocol commenced after institutional research ethics approval was granted. Eligible patients had pathologically-confirmed newly diagnosed SCLC with extensive stage disease at the time of diagnosis, adequate pulmonary function tests (FEV-1 >1.0 L, DLCO >50%), age at least 18 years, Karnofsky Performance Status ⩾70, documented objective response to at least one cycle of chemotherapy, and signed a study-specific consent form. Patients were excluded if they had undergone complete or

Results

Between March 2008 and September 2009, 33 patients were accrued to the protocol. All patients signed a study-specific consent form prior to commencing RT study. One patient was found to have inadequate pulmonary function tests after providing signed consent for the study and did not receive chest RT, leaving 32 patients who underwent study thoracic RT. Patient characteristics are summarized in Table 1. Table 2 summarizes chemotherapy agents prescribed and observed disease response details.

Discussion

The majority of ES-SCLC patients demonstrate a response to induction chemotherapy treatments, but complete responses are rare, and post-chemotherapy recurrences are the norm. A recent report suggests the prognostic value of a demonstrated radiologic response to chemotherapy on CT and PET imaging [9]. The addition of post-chemotherapy RT to regions of residual disease in ES-SCLC patients who respond to chemotherapy may provide further local control and possibly survival benefits by controlling

Conclusions

In this study, post-chemotherapy chest RT in ES-SCLC patients who responded to chemotherapy was associated with symptomatic chest recurrences in only 5 of 32 irradiated patients. This level of symptomatic local control will need confirmation in ongoing randomized trials of post-chemotherapy chest RT for ES-SCLC.

Conflict of interest statement

None of the authors of this work have any potential conflicts of interest to declare.

Acknowledgment

This work was supported by a grant from the Cross Cancer Institute Clinical Research Unit.

References (15)

P. Warde et al.
Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis
J Clin Oncol
(1992)
J.P. Pignon et al.
A meta-analysis of thoracic radiotherapy for small-cell lung cancer
N Engl J Med
(1992)
A.P. Meert et al.
Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis
BMC Cancer
(2001)
A. Auperin et al.
Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group
N Engl J Med
(1999)
B. Slotman et al.
Prophylactic cranial irradiation in extensive small-cell lung cancer
N Engl J Med
(2007)
B. Emami et al.
Tolerance of normal tissue to therapeutic irradiation
Int J Radiat Oncol Biol Phys
(1991)
D.C. Ihde et al.
Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer
J Clin Oncol
(1994)

There are more references available in the full text version of this article.

Cited by (82)

Feasibility and long-term outcomes of post-chemotherapy-based consolidation radiotherapy in extensive stage small-cell lung cancer
2023, Journal of the National Cancer Center
The target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC.
All ES-SCLC patients without initial brain metastases who completed ≥ 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT.
A total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9–39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1–11.2 months) and 16.2 months (IQR, 9.9–24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without synchronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12–0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13–1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred.
Small-field consolidation RT based on post-chemotherapy volume is safe and can significantly improve local control in ES-SCLC.
Radiation therapy for extensive-stage small-cell lung cancer in the era of immunotherapy
2022, Cancer Letters
Citation Excerpt :
In the absence of immunotherapy, Jeremic used accelerated hyperfractionated RT (54Gy/36f bid), and Slotman adopted 30Gy/10f as the TRT fraction. Overall, TRT dose was 30–60Gy/1.5∼3Gy for ES-SCLC [16–18,22–29]. A retrospective analysis of the NCDB found that TRT≥ 45Gy was an independent factor for better survival than TRT< 45Gy (HR = 0.78, P < 0.001) [50].
Unlike non-small-cell lung cancer (NSCLC), the progression of small-cell lung cancer (SCLC) is slow. Extensive-stage SCLC (ES-SCLC) is a serious threat to human health, with a 5-year survival rate of <7%. Chemotherapy has been the first-line treatment for the past 30 years. The anti-PD-L1 checkpoint blockades durvalumab and atezolizumab have greatly prolonged overall survival and have become the standard first-line therapy for ES-SCLC since the CASPIAN and IMpower133 trials. In the era of chemotherapy, radiation therapy (RT), including thoracic radiation therapy (TRT) and brain radiation therapy (BRT), has shown clinical effects in randomized and retrospective studies on ES-SCLC. RT-immunotherapy has shown exciting synergistic effects in NSCLC. For ES-SCLC, the clinical effects of combining TRT/BRT with immunotherapy have not yet been systematically explored. In this review, we found that studies on RT-immunotherapy in ES-SCLC are relatively few and limited to early phase studies focusing on toxicity. The efficacy and safety profiles of early phase studies encourage prospective clinical trials. In this review, we discuss the best population, optimum TRT dose, proper TRT time, and strategies for reducing radiation-induced neurotoxicity. Furthermore, we suggest that biomarkers and patient performance status should be fully assessed before RT-immunotherapy treatment. Prospective trials are needed to provide more evidence for RT-immunotherapy applications in ES-SCLC.
American Radium Society Appropriate Use Criteria on Radiation Therapy for Extensive-Stage SCLC
2021, Journal of Thoracic Oncology
The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy.
The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC.
Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing.
Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.
Radiotherapy for primary tumor in lung cancer with synchronous metastases: Overview from the past and proposal for the future
2020, Cancer/Radiotherapie
Citation Excerpt :
TRT is a mainstay in the treatment of localized-stages SCLC, as it early demonstrated a benefit in local control and OS compared with CHT alone [22]. After multiple retrospective studies [23,24] and a phase 2 prospective non-randomized trial [25] positioning thoracic RT as an option in ES-SCLC with synchronous distant metastases, its place in this indication has been consolidated and supported by 2 prospective phase 3 randomized trials: a first trial by Jeremic et al. [17], comparing TRT (54 Gy/36 fractions) with concomitant CHT (TRT/CHT) to CHT alone in 210 patients.
The management of metastatic lung cancers, either of the small-cell (SCLC) or the non-small cell (NSCLC) subtype, largely based on systemic treatments so far, has been the subject of breakthrough advances over the past few years, with notably the wide use of immunotherapy changing the landscape of these harmful prognosis diseases. In parallel with this major progress, the increasing use of radiotherapy (RT) for the treatment of the primary thoracic lesion ± the distant lesions, may contribute to improving the condition of these metastatic patients, both in terms of progression-free survival (PFS) and overall survival (OS). This review proposes to summarize and explain the findings provided by the different studies published in the last years experiencing RT of the primary tumor in metastatic lung cancers, either associated or not with the local ablative treatment of a low number of distant lesions. It will also expose the respective limits encountered in these studies and, in the light of all these elements, suggests various promising issues and fields of research for the future.
La prise en charge des cancers du poumon au stade métastatique, qu’il s’agisse des cancers du poumon à petites cellules (CBPC) ou non-à-petites cellules (CBNPC), reposant jusqu’ici sur les traitements systémiques, a bénéficié au cours des dernières d’avancées thérapeutiques majeures, avec notamment la percée des immunothérapies qui bouleverse le paysage de ces maladies au pronostic sombre. En parallèle de ces progrès majeurs, le recours grandissant à la radiothérapie pour le traitement de la lésion primitive thoracique éventuellement associé à celui des lésions métastatiques, constitue l’un des éléments susceptibles d’améliorer les résultats, à la fois en termes de survie sans progression et de survie globale. Cette revue de la littérature propose de récapituler les données à disposition dans les études publiées ces dernières années expérimentant la radiothérapie comme traitement de la tumeur primitive thoracique dans les cancers du poumon métastatiques, associée ou non au traitement des métastases. Elle expose également les limites respectives rencontrées dans ces études et, à la lumière de ces dernières, essaie de proposer des pistes de recherche prometteuses à l’avenir.
Efficacy and safety of thoracic radiotherapy in extensive-stage small-cell lung cancer patients receiving first-line immunotherapy plus chemotherapy: a propensity score matched multicentre retrospective analysis
2024, Radiation Oncology
Factors associated with overall survival, progression-free survival and toxicity in patients with small cell lung cancer and thoracic irradiation in a clinical real-world setting
2023, Radiation Oncology

View all citing articles on Scopus

View full text

Phase II trialClinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer

Abstract

Background and purpose

Materials and methods

Results

Conclusions

Section snippets

Eligibility

Results

Discussion

Conclusions

Conflict of interest statement

Acknowledgment

Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis

J Clin Oncol

A meta-analysis of thoracic radiotherapy for small-cell lung cancer

N Engl J Med

Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis

BMC Cancer

Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group

N Engl J Med

Prophylactic cranial irradiation in extensive small-cell lung cancer

N Engl J Med

Tolerance of normal tissue to therapeutic irradiation

Int J Radiat Oncol Biol Phys

Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer

J Clin Oncol

Phase II trial
Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer