Limited-stage SCLC Research Articles

MA17.05 Longitudinal MRD Monitoring Enhances Prognosis Prediction in 105 Patients with Limited-Stage SCLC Receiving Concurrent Chemoradiotherapy

MA17.05 Longitudinal MRD Monitoring Enhances Prognosis Prediction in 105 Patients with Limited-Stage SCLC Receiving Concurrent Chemoradiotherapy

LBA81 Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial

LBA81 Durvalumab (D) as consolidation therapy in limited-stage SCLC (LS-SCLC): Outcomes by prior concurrent chemoradiotherapy (cCRT) regimen and prophylactic cranial irradiation (PCI) use in the ADRIATIC trial

PP01.90 Real-world Demographics, Clinical Characteristics, Treatment Patterns and Clinical Outcomes for US Patients with Limited-Stage SCLC (LS-SCLC)

PP01.90 Real-world Demographics, Clinical Characteristics, Treatment Patterns and Clinical Outcomes for US Patients with Limited-Stage SCLC (LS-SCLC)

Tazemetostat in combination with topotecan and pembrolizumab in patients with recurrent small cell lung cancer.

TPS8130 Background: Small-cell lung cancer (SCLC) is the most fatal type of lung cancer characterized by exquisite chemo-sensitivity at diagnosis and chemoresistance at relapse. Despite a highly mutated genome, patients with SCLC derive little benefit from immunotherapy. EZH2 (enhancer of zeste homolog 2) is a master epigenetic regulator of SCLC neuroendocrine cell fate and plasticity. EZH2 inhibition 1) promotes upregulation of Schlafen 11 (SLFN11) which irreversibly blocks replication in response to DNA damaging agents and 2) enhances intrinsic immune signaling, leading to constitutive MHC I recovery, sensitizing resistant SCLC models to DNA damaging chemotherapy and immunotherapy. Tazemetostat is a selective oral EZH2 inhibitor. Methods: This is an investigator-initiated, NCI Cancer Therapy Evaluation Program (CTEP) sponsored, phase I dose escalation and dose expansion study which will evaluate safety and tolerability of combination of tazemetostat with topotecan, a selective TOP1 inhibitor, and programmed cell death protein 1 (PD-1) inhibitor antibody pembrolizumab. Adult patients with relapsed/recurrent SCLC after at least platinum doublet (limited stage-SCLC) or chemo-immunotherapy (extensive stage-SCLC) and ECOG performance 0-1 are eligible. The regimen design involves a 7-day “run-in” of oral tazemetostat BID followed by 21-day cycles of tazemetostat (1-21 days), intravenous (IV) topotecan (day 1-5) and IV pembrolizumab (Day 1). The dose escalation cohort aims to determine safety and optimal doses of tazemetostat and topotecan (with standard dose of pembrolizumab) using a 3+3 design by assessing for dose limiting toxicities. The dose expansion cohort aims to assess safety, tolerability and preliminary efficacy of the combination in 15 additional patients with relapsed SCLC. The study involves collection of mandatory biopsies at pre-treatment and post-treatment (cycle 1) to gain insights into mechanism of action and resistance of the combination using single cell and spatial transcriptomic approaches. For more questions regarding enrollment and eligibility please contact Rasa.vilimas@nih.gov or anish.thomas@nih.gov . Clinical trial information: NCT05353439 .

Effect of FDG PET-CT for Staging and Radiotherapy Planning – A Comparison of Cohorts From Two Randomized Trials of Thoracic Radiotherapy in Limited-Stage SCLC

Introduction18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival. MethodsPatients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4–7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]). ResultsA total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, p = 0.043), less grade >=1 pneumonitis (5% versus 16%, p = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, p = 0.59) or progression-free survival (11 versus 11 mo, p = 0.23). ConclusionsUsing PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.

Pamiparib as consolidation treatment after concurrent chemoradiotherapy of limited-stage small cell lung cancer: a single-arm, open-label phase 2 trial

BackgroundSmall cell lung cancer (SCLC) is highly invasive with poor prognosis, and its treatment has historically been hindered due to the absence of targetable driver genomic alterations. However, the high genomic instability and replication stress in SCLC have made poly(ADP-ribose) polymerases (PARPs) inhibitors a focus of research. Pamiparib is an orally available PARP1/2 inhibitor with high selectivity, strong PARP trapping activity, and excellent brain penetration. Utilizing pamiparib as consolidation maintenance therapy in limited-stage SCLC holds promise for improving survival outcomes and offering a viable therapeutic approach.MethodsThis single-arm, open-label phase II trial will enroll patients aged 18–75 years with histologically/cytologically confirmed, limited-stage SCLC who have not progressed following definitive platinum-based cCRT and have an ECOG PS of 0 or 1. Patients will be excluded if they have histologically confirmed mixed SCLC or NSCLC, or have undergone previous tumor resection, or can be treated with surgery or stereotactic body radiation therapy/stereotactic ablative radiation therapy. Participants will receive pamiparib 40 mg twice daily every 3 weeks within 2 to 6 weeks after cCRT for up to 1 year or until disease progression according to RECIST v1.1. The primary endpoint is the 1-year progression-free survival (PFS) rate assessed by investigators per RECIST v1.1. Secondary endpoints include PFS, objective response rate, and duration of response assessed by investigators per RECIST 1.1, overall survival, time to distant metastasis, and safety.DiscussionThe study will provide valuable data on the feasibility, safety, and effectiveness of pamiparib as a consolidation therapy after cCRT in patients with LS-SCLC. The correlation between molecular typing or gene expression profile of the disease and curative response will be further explored.Trial registrationNCT05483543 at clinicaltrials.gov.

Abstract 1125: TNIK induced chemoradiation resistance in small cell lung cancer

Abstract Chemoradiation (CRT) is the standard first-line therapy for limited stage small cell lung cancer (LS-SCLC), which is characterized by early metastasis, intrinsic-acquired CRT resistance and tumor recurrence. CRT confers a 20-25% 5-year overall survival in patients with LS-SCLC. In this study, we utilized patient-derived xenograft (PDX) models to demonstrate CRT resistance of SCLC and identified CRT resistance candidate genes from various SCLC PDX that represent the majority of molecular subtypes (n=4 that include SCLC-A and SCLC-N subtypes). RNA-seq data identified TNIK (Traf2- and Nck-interacting kinase) as one such gene that is consistently upregulated in SCLC PDXs exposed to CRT compared to single modality treatments. Copy number gains of TNIK were also present in human SCLC samples. Overcoming this CRT resistance is crucial in improving treatment outcomes and patient survival. Genetic depletion or pharmacological inhibition of TNIK reduced the in vitro clonogenic survival of TNIKhigh SCLC cells, NCI-H446 and makes them increasingly sensitive to CRT. In vivo, pharmacological inhibition of TNIK with the inhibitor NCB-0846, enhances the CRT sensitivity of NCI-H446 cell line-derived xenografts (CDX) in NOD SCID immunodeficient mice. Furthermore, pharmacological inhibition of TNIK in vivo demonstrated sensitivity to CRT in LX33 PDX. In conclusion, our results indicate that TNIK plays a role in conferring resistance to CRT in vitro in SCLC cell lines and in vivo in SCLC CDX and PDX models and therefore, can be a potential therapeutic target in limited stage SCLC. Citation Format: Dipanwita Dutta Chowdhury, Eddie Imada, Nick Connis, Triet Nguyen, Jinhee Chang, Danielle Council, Audrey Lafargue, Mohammad Rezaee, Phuoc T. Tran, Luigi Marchionni, Christine L. Hann. TNIK induced chemoradiation resistance in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1125.

EP13.04-04 Preliminary Results of a Prospective Trial of Hypofractionated Radiotherapy Versus Hyperfractionated Radiotherapy for Limited-stage SCLC

EP13.04-04 Preliminary Results of a Prospective Trial of Hypofractionated Radiotherapy Versus Hyperfractionated Radiotherapy for Limited-stage SCLC

Facility-Level Analysis of Twice Daily Radiation Utilization for Limited Stage Small Cell Lung Cancer

Treatment of limited stage SCLC (LS-SCLC) with twice daily (BID) fractionation (fx) to 45 Gy remains the standard of care for many decades. However, many patients receive once daily (QD) treatment as outcomes appear similar. Recent data have suggested that dose escalation to 60 Gy BID may improve outcomes, stressing the importance of BID delivery for SCLC. In this study, we examined the use of BID fractionation across treatment facilities and hypothesized that a substantial number of centers may never utilize BID treatment. The National Cancer Database (NCDB) was used to identify U.S. facilities treating LS-SCLC patients with definitive chemoradiation from 2004 to 2019. Included patients had stage I-III disease, received doublet chemotherapy, and did not undergo surgery. All patients received thoracic radiation therapy (RT), defined as QD (59.4-70.2 Gy in 30-39 fx) or BID (45 Gy in 30 fx). Other RT regimens were excluded. Facilities were classified into two cohorts (BID-treating and QD-only) based on whether or not at least one patient received BID treatment over the study period. Facility-level statistics including facility type, geographic location, and facility volume were analyzed. Predictors of BID-treating facility classification were determined using Chi-squared tests and uni/multivariable logistic regression. From 2004 to 2019, 22,545 LS-SCLC patients were treated by 1,222 facilities. Of the 1,222 facilities, 832 (68%) were BID-treating facilities while 391 (32%) were QD-only facilities. On univariable analysis, facility type (community cancer program, comprehensive community cancer program, integrated network cancer program, or academic program; p = 0.783) and geographic location (Northeast, Midwest, South, West; p = 0.417) were not associated with classification as a BID-treating facility. In contrast, facility volume was significantly associated with classification as a BID-treating facility, with BID use noted in 42.8% of the lowest quartile volume facilities vs. 84.0% of the highest quartile volume facilities (p<0.001). Dichotomized facility type (academic vs. non-academic), geographic location (South vs. other), and facility volume (greater or less than median volume) were included in a multivariable analysis. Facility volume (p<0.001) remained significant while facility type (p = 0.956) and facility location (p = 0.516) remained insignificant. Despite evidence supporting BID fractionation as the standard of care for LS-SCLC, 32% of facilities have never delivered BID treatment over the 15-year study period. Facilities with a low volume of patients are most likely to use QD-only. Barriers to BID treatment adoption will need to be overcome if dose escalated BID fractionation defines a new standard of care for LS-SCLC.

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

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.

Impact of systemic immune-inflammation index in patients with limited-stage small cell lung cancer.

e20626 Background: The systemic immune-inflammation index (SII) has been suggested as a prognostic marker in several solid malignant neoplasms. However, there are few studies on the prognostic value of SII in patients with limited-stage SCLC. This study explored the impact of SII on overall survival (OS) and progression-free survival (PFS) in patients with limited-stage small cell lung cancer, and compared the predictive ability of SII and platelet/lymphocyte ratio (PLR) to find a better prognostic marker. Methods: In total, 572 patients with new diagnosis of limited-stage SCLC were included in this study. The optimal threshold of SII and PLR were determined using the outcome(OS)-based method by maximizing the log-rank test statistic and the survival differences.The predictive ability of SII and PLR were compared by drawing the continuous time-dependent receiver operating characteristic curves (time-dependent ROC). Logistic multivariable analysis was performed to identify factors associated with high SII. Propensity score matching (PSM) was used to balance confounders between groups and adjust observed selection bias. Kaplan-Meier methods and Cox proportional hazards models were used to assess the impact of pre-treatment SII on OS and PFS. Results: The median age of the whole group was 60.0 (25.0-81.0) years, and the median follow-up time was 56.5 (2.5-95.4) months. The optimal cutoff value of SII and PLR were 760.6 and 137.3, respectively. The area under the time-dependent ROC curves of SII and PLR in 1-, 2- and 3-year were 0.727, 0.708, 0.680 and 0.680, 0.669, 0.649, respectively. The high SII group was correlated with pleural effusion (P = 0.001), T stage (P = 0.009), N stage (P = 0.048), and pretreatment serum sodium (P = 0.003). The median OS and PFS of the whole group was 26.0 months (95%CI 23.8-28.2) and 13.0 months (95%CI 11.3 -14.7), and the 1-, 3-, 5-year OS rates and the 1-, 3-, 5-year PFS rates were 81.1%, 35.5%, 27.1% and 52.8%, 24.8%, 19.9%, respectively.There were 414 patients after PSM. In multivariable survival analysis, SII remained an independent prognostic factor for OS (HR1.792; 95%CI 1.416-2.268; P &lt; 0.001) and PFS (HR1.410; 95%CI 1.043-1.906; P = 0.025). Conclusions: Elevated SII is an independent adverse prognostic factor in patients with limited-stage SCLC and is superior to PLR in terms of prognostic ability.

Real world outcomes of trilaciclib in ES-SCLC.

e20637 Background: Carboplatin, etoposide, and atezolizumab (PEA) is the most widely used combination for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). Chemotherapy-induced myelosuppression is a common sequalae that is traditionally managed with lineage-specific supportive care modalities. Studies that evaluated trilaciclib versus placebo in combination with chemotherapy demonstrated statistically significant improvements in the duration of severe neutropenia (SN), defined as ANC &lt; 500 cells/µL, in cycle 1 and incidence of SN as a result of its transient myeloprotective effects. There remains considerable controversy in the adoption of trilaciclib as a supportive medication in clinical practice. The objective of this quality assessment study was to assess utility of trilaciclib in real-world ES-SCLC patients. Methods: This was a single center study with quasi-experimental design comparing patients with confirmed ES-SCLC who received trilaciclib + PEA (PEAT) from April 2021 to July 2022 versus those who received PEA without trilaciclib (PEA) from February 2020 to February 2021. Patients with limited-stage SCLC, prior treatment with immunotherapies, carboplatin dose AUC &lt; 3.5 with cycle 1, and active clinical trial enrollment were excluded. The primary endpoint evaluated was incidence of SN after cycle 1 and during treatment period. Additional measures related to myelopreservation and patient outcomes were assessed as secondary endpoints. Demographic data was analyzed using descriptive statistics. Dichotomous and continuous variables were compared by Mann-Whitney U or one-sided Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier (KM) estimate. Results: 34 patients received PEAT and 44 patients received PEA. Demographic and baseline clinical characteristics were similar between both cohorts except for older median age of patients (69 years old vs 64 years old) and higher proportion of male patients (65% vs 39%) in the trilaciclib cohort. Even though there was a numerically lower rate of SN (3%) and hospitalization due to febrile neutropenia (FN) or infection (6%) in the PEAT versus the PEA (18%;11%) cohort, statistical significance was not met (p = 0.07;p = 0.065). Likewise, incidence of FN, platelet transfusion requirements, all-cause chemotherapy reductions, and treatment delays were not statistically different. However, the PEAT cohort as compared to PEA experienced a statistically significant reduction in red blood cell transfusion requirements (3% vs 23%; p = 0.02) and grade 3-4 anemia (6% vs 25%; p = 0.03). PFS and OS between the two cohorts were not statistically different. Conclusions: Based on this single center retrospective study, use of trilaciclib appears to confer improvement in the safety profile of PEA without negatively impacting survival outcomes. Therefore, results of this study support the integration of trilaciclib with PEA for ES-SCLC.

Abstract 3906: The mRNA translational plasticity of small cell lung carcinoma is associated with its phenotypic transdifferentiation

Abstract Small cell lung carcinoma(SCLC), classified as a recalcitrant cancer type, accounts for 13-15% of all lung cancers with a median overall survival less than 10 months in patients with extensive stage SCLC. SCLC was once considered as molecularly homogeneous due to nearly universal loss of TP53 and RB1, whereas subsets of MYC-driven, non-neuroendocrine (non-NE) SCLC variants, possess chemoresistance, suggesting its high plasticity and intertumoral heterogeneity related to rapid refractory to first-line chemotherapies. Current pathognomonic classification stratifies SCLC into two NE subtypes (ASCL1+, NEUROD1+) and two non-NE subtypes (POU2F3+ and triple negative), associated with different expression patterns of MYC family proteins. MYC is a master regulator of mRNA translation, whether translational regulation actively tunes SCLC plasticity and the associated chemosensitivity remains an enigma. Here, we delineate the translation landscape of NE and non-NE SCLC cells by using paired human NE SCLC cell line and constitutive or induced non-NE SCLC cells. As expected, non-NE SCLC cells are more resistant to the clinically relevant first-line chemotherapy than NE SCLC cells. With polysome profiling in combination with polysome RNA-seq, we showed differential expression at both transcription- and translation-level. However, transcription-level changes minimally overlapped with the translational changes between NE and non-NE SCLC cells, with a global reduction of translation activity observed in non-NE SCLC cells. Through analyzing the polysome profiles, we observed a striking accumulation of 60S monosomes and diminishment of 80S ribosomes derived from non-NE SCLC cells compared to those from NE SCLC cells. This unique translational pattern in non-NE SCLC cells was correlated with an increased expression of eIF6, a ‘sitting on the bench’ member of eukaryotic initiation factor (eIF) family. The eIF6 couples 60S monosome maturation and recycling, enrolling a quintessential role in functional 80S ribosome formation. Positive correlation between eIF6 expression and non-NE SCLC tumors was observed in 81 tumor samples derived from patients with limited stage SCLC and CCLE cell consortium, in which c-MYC expression was also positively correlated with eIF6 level. By using both ultracentrifugation and fraction analysis from polysome profiling, we found that less association of eIF6 with 60S may mitigate 80S ribosome assembly in non-NE SCLC cells. In addition, in vivo xenograft models showed that eIF6 expression was higher in residual tumors upon chemotherapy. Taken together, these data revealed an eIF6-dependent translational regulation in non-NE transdifferentiation of SCLC subtypes, suggesting an underappreciated function of translational regulation of SCLC plasticity and the potential therapeutic value of eIF6 for overcoming SCLC resistance to chemotherapy. Citation Format: Haoning Peng, Mengyao Wang, Lu Li, Lunxu Liu, Shensi Shen. The mRNA translational plasticity of small cell lung carcinoma is associated with its phenotypic transdifferentiation. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3906.

168P Demographics, clinical characteristics, treatment (tx) patterns and clinical outcomes for patients (pts) with limited-stage SCLC (LS-SCLC)

168P Demographics, clinical characteristics, treatment (tx) patterns and clinical outcomes for patients (pts) with limited-stage SCLC (LS-SCLC)

Age-Stratified Analysis of First-Line Chemoimmunotherapy for Extensive-Stage Small Cell Lung Cancer: Real-World Evidence from a Multicenter Retrospective Study.

Chemoimmunotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage small cell lung cancer (ES-SCLC) in two phase III trials. They set the age-stratified subgroup analyses at 65 years; however, over half of the patients with lung cancer were newly diagnosed at ≥75 years in Japan. Therefore, treatment efficacy and safety in elderly patients ≥ 75 years with ES-SCLC should be evaluated through real-world Japanese evidence. Consecutive Japanese patients with untreated ES-SCLC or limited-stage SCLC unfit for chemoradiotherapy between 5 August 2019 and 28 February 2022 were evaluated. Patients treated with chemoimmunotherapy were divided into the non-elderly (<75 years) and elderly (≥75 years) groups, and efficacy, including PFS, OS, and post-progression survival (PPS) were evaluated. In total, 225 patients were treated with first-line therapy, and 155 received chemoimmunotherapy (98 non-elderly and 57 elderly patients). The median PFS and OS in non-elderly and elderly were 5.1 and 14.1 months and 5.5 and 12.0 months, respectively, without significant differences. Multivariate analyses revealed that age and dose reduction at the initiation of the first chemoimmunotherapy cycle were not correlated with PFS or OS. In addition, patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) = 0 who underwent second-line therapy had significantly longer PPS than those with ECOG-PS = 1 at second-line therapy initiation (p < 0.001). First-line chemoimmunotherapy had similar efficacy in elderly and non-elderly patients. Individual ECOG-PS maintenance during first-line chemoimmunotherapy is crucial for improving the PPS of patients proceeding to second-line therapy.

Treatment Outcomes of Older Participants in a Randomized Trial Comparing Two Schedules of Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC

IntroductionHalf of the patients with limited-stage SCLC (LS SCLC) are above or equal to 70 years old, but they account for less than 20% of participants in most trials. Comorbidities and reduced organ and physical function might lead to more treatment toxicity, and population-based studies indicate that fewer older than younger patients with LS SCLC receive standard chemoradiotherapy, although there is limited evidence for such a policy. MethodsWe compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health-related quality of life, and treatment outcomes between patients above or equal to 70 years old and those younger than 70 years old in an open-label, randomized phase II trial comparing twice-daily thoracic radiotherapy of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent i.v. cisplatin (75mg/m2) or carboplatin (AUC 5-6 mg/ml x min) day 1 and i.v. etoposide (100 mg/m2) day 1-3 chemotherapy. This trial is registered at ClinicalTrials.gov (NCT02041845). ResultsA total of 170 patients who were above or equal to 18 years old and had performance status of 0 to 2 were randomized. Of these, 53 patients (60 Gy: 25, 45 Gy: 28) were above or equal to 70 years old and 117 (60 Gy: 64, 45 Gy: 53) were younger. There were no differences in baseline characteristics, treatment completion rates, toxicity, or response rates across the age groups. Health-related quality of life mean scores were similar during year one, but older patients reported more decline on functional scales than younger patients during year two. Overall survival was shorter for older patients, whereas there was no difference in progression-free survival or time to progression. ConclusionsPatients above or equal to 70 years old tolerated concurrent twice-daily chemoradiotherapy and achieved similar disease control as younger patients, indicating older patients should receive the same treatment as younger patients.

Durvalumab plus platinum-etoposide chemotherapy for extensive-stage small cell lung cancer: a retrospective real-world study.

Immune checkpoint inhibitor plus platinum-etoposide (PE) improved overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). While the CASPIAN trial demonstrated the efficacy of durvalumab plus PE, the clinical trial results may not be representative of the general, real-world population because clinical trials often have strict inclusion and exclusion criteria. We herein report the efficacy and safety of durvalumab plus PE in patients with ES-SCLC in real-world, clinical practice. The present, monocentric, retrospective study evaluated patients with ES-SCLC or recurrent, limited-stage SCLC who received durvalumab plus PE between September 2020 and February 2023. The efficacy and incidence of adverse events (AEs) were also evaluated. The study included 40 patients, of whom 17 were elderly (age >70 years), and 15 had performance status (PS) 2 or 3. The median follow-up time was 13.0 months [95% confidence interval (CI): 8.0-22.2 months]. The objective response rate was 80.0% (95% CI: 63.1-91.6%), and the disease control rate was 88.6% (95% CI: 73.3-96.8%). The median progression-free survival (PFS) was 5.9 months (95% CI: 4.9-6.9), and the median OS was 25.4 months (95% CI: 4.6-46.2). Factors such as advanced age, poor PS, and presence of brain metastases were not associated with lower PFS and OS. Twenty-six patients (65.0%) experienced grade 3 or higher AEs, mainly hematological toxicity. AEs leading to treatment discontinuation occurred in three patients (8%). Durvalumab plus PE in patients with ES-SCLC showed good efficacy and safety according to our real-world data, suggesting that this treatment is well tolerated in clinical practice, even in elderly patients and those with poor PS.

Prognostic ability of lung immune prognostic index in limited-stage small cell lung cancer

BackgroundLung immune prognostic index (LIPI) is a prognostic marker of extensive-stage small cell lung cancer (ES-SCLC) patients received immunotherapy or chemotherapy. However, its ability in limited-stage SCLC (LS-SCLC) should be evaluated extensively.MethodsWe retrospectively enrolled 497 patients diagnosed as LS-SCLC between 2015 and 2018, and clinical data included pretreatment lactate dehydrogenase (LDH), white blood cell count, and absolute neutrophil count levels were collected. According to the LIPI scores, the patients were stratified into low-risk (0 points) and high-risk (1–2 points). The correlations between LIPI and overall survival (OS) or progression-free survival (PFS) were analyzed by the Cox regression. Additionally, the propensity score matching (PSM) and inverse probability of treatment weight (IPTW) methods were used to reduce the selection and confounding bias. A nomogram was constructed using on multivariable Cox model.ResultsTwo hundred fifty and 247 patients were in the LIPI high-risk group and low-risk group, and their median OS was 14.67 months (95% CI: 12.30–16.85) and 20.53 months (95% CI: 17.67–23.39), respectively. In the statistical analysis, High-risk LIPI was significantly against worse OS (HR = 1.377, 95%CI:1.114–1.702) and poor PFS (HR = 1.338, 95%CI:1.1–1.626), and the result was similar after matching and compensating with the PSM or IPTW method. A novel nomogram based on LIPI has a decent level of predictive power.ConclusionLIPI stratification was a significant factor against OS or PFS of LS-SCLC patients.

Simultaneous Integrated Boost vs. Routine IMRT in Limited-Stage Small-Cell Lung Cancer: An Open-Label, Non-Inferiority, Randomized, Phase 3 Trial—Interim Analysis

<h3>Purpose/Objective(s)</h3> Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy. <h3>Materials/Methods</h3> This randomized, non-inferiority, open-label, phase 3 study was done in a single institution in China. Patients aged 18–70 years who was diagnosed with treatment-naïve and confirmed limited-stage SCLC were eligible. All participants received 4-6 courses of intravenous cisplatin 75 mg/m² or carboplatin (area under the curve 5–6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m² on days 1–3 every 3 weeks. Participants were randomly assigned (1:1) stratifying for the timing of thoracic radiation therapy to receive simultaneous integrated boost radiotherapy (PGTV 60.2Gy/2.15Gy/28F, PTV 50.4Gy/1.8Gy/28F) or conventional fractionated radiotherapy (PTV 60Gy/2Gy/30F) to the primary lung tumor and CT positive lymph node metastases. Responders were offered prophylactic cranial irradiation of 25Gy/2.5Gy/10F.The primary endpoint was 2-year progression-free survival, the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity. <h3>Results</h3> Between February 2017, and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among which 106 patients in the conventional fractionated radiotherapy group,110 patients in the SIB group. The 2-year progression-free survival rates were 45.2% vs 38.3% and the median progression-free survival was 18 months (95%CI:9.06-26.39) in the conventional fractionated radiotherapy group versus 17 months(95%CI:11.47-22.53) in the SIB group (P=0.2, HR 1.22,95%CI:0.87-1.72). The 2-year overall survival rates were 73.5% VS 60.9% (P=0.14, HR 1.35,95%CI:0.90-2.04). The 2-year local-regional recurrence-free survival rates were 68.7% VS 69.9% (P = 1.0, HR = 0.98, 95% CI = 0.62-1.56). The most common grade 3–4 adverse events were myelosuppression (21.7% vs 15.4%, P = 0.83), radiation pneumonitis (4.7% vs 2.7%, P = 0.44), radiation esophagitis (3.8% vs 1.8%, P = 0.51). <h3>Conclusion</h3> Simultaneous integrated boost radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with limited-stage small cell lung cancer. Further enrollment and follow-up are warranted to confirm these findings in this ongoing trial. This trial is registered at ClinicalTrials.gov, NCT04500145.

An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer – A Mainstay of Treatment or a Modality in Decline?

AimsSmall cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC. Materials and methodsThe search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. ClinicalTrials.gov was also queried for relevant trials. ResultsThoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era. ConclusionRadiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.