Extensive Stage Small Cell Lung Research Articles

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate. Utilizing an institutional database search tool, we queried the electronic medical record to identify patients with SCC or neuroendocrine carcinoma of the prostate who had been treated with atezolizumab and chemotherapy. We recorded patient characteristics, including age, pathology, and disease extent. Treatment characteristics included number of prior treatments, use of concominant androgen deprivation, number of cycles of immunotherapy, and prior systemic therapies (including those for adenocarcinoma of the prostate). Progression free survival (PFS) and overall survival (OS) were the primary outcomes. We identified seven men who received atezolizumab for metastatic prostate cancer with a small cell or neuroendocrine component. In six of the seven patients, the combination of carboplatin, etoposide, and atezolizumab was the first-line of treatment after diagnosis of small cell or neuroendocrine carcinoma. Two of the seven patients had de novo small cell/neuroendocrine pathology, while the other five had transformation from a preexisting adenocarcinoma. In the patients who received chemotherapy plus immunotherapy in the first-line setting, at a median follow-up of 6.5 months (range: 1.5-15.1) the median PFS was 3.4 months and median OS was 8.4 months. Small cell or neuroendocrine carcinoma of the prostate was associated with poor survival outcomes despite adding immunotherapy (atezolizumab) to chemotherapy (carboplatin and etoposide). To our knowledge, there has been no demonstrable benefit of adding immunotherapy to chemotherapy in this setting.

136 - Assessing outcomes in patients that received consolidation radiotherapy following palliative chemotherapy in patients diagnosed with extensive stage small cell lung cancer

136 - Assessing outcomes in patients that received consolidation radiotherapy following palliative chemotherapy in patients diagnosed with extensive stage small cell lung cancer

Protein expression of programmed cell death ligand 1 and ligand 2 and their prognostic values in extensive-stage small cell lung cancer.

e20593 Background: The receptor-ligand interaction between programmed cell death protein-1 (PD-1) and its ligands (PD-L1 and PD-L2) plays a critical role in tumor immune evasion and has become a therapeutic target in a number of cancer types, including extensive stage small cell lung cancer (ES-SCLC). While there are some published data on PD-L1 expression in ES-SCLC, the results vary with different laboratory assays or thresholds of positivity employed. Data on PD-L2 expression is very limited in ES-SCLC. The prognostic values of these biomarkers are not well understood. The current study aims to address this data gap. Methods: A retrospective cohort study of patients with ES-SCLC receiving usual care in the clinical setting in Denmark was conducted. Formalin-fixed paraffin embedded (FFPE) tumor tissue samples and data on patient characteristics and clinical outcomes were obtained for the patient population. Protein expression of PD-L1 and PD-L2 was determined by immunohistochemistry (IHC), and a combined positive score (CPS, the percentage of tumor cells and mononuclear inflammatory cells expressing the biomarker at any intensity out of the total number of tumor cells) of ≥1 was used to define biomarker positivity. Kaplan-Meier plots and Cox proportional hazard models were employed to assess the relationship between PD-L1 and PD-L2 protein expression and overall survival (OS). Results: Among the 80 patients with ES-SCLC included in this study, 25 and 29 were positive for PD-L1 and PD-L2, respectively (Table). A total of 68 patients had concordant expression status of PD-L1 and PD-L2 (21 as double positive and 47 as double negative). There was a significant association between PD-L1 positivity and longer OS, which persisted after adjustment for age and stage at SCLC diagnosis, performance score, prior exposure to chemotherapy, and lactate dehydrogenase levels (Table). Similar results were observed for PD-L2 (Table), and the data did not suggest any additional prognostic value of PD-L2 expression independent of PD-L1 expression. Conclusions: PD-L1 and PD-L2 positivity was both observed, and highly correlated with each other, in approximately one third of the ES-SCLC tumor samples tested. Patients with PD-L1 or PD-L2 positive tumors have significantly longer OS than those with negative tumors in this study, independent of other known prognostic factors.[Table: see text]

Real-world treatment patterns, clinical outcomes, and health care resource utilization in extensive-stage small cell lung cancer in Canada.

e20575 Background: Extensive stage small cell lung cancer (ES-SCLC) patients face a high risk of recurrence and a uniformly poor prognosis. Real-world evidence related to treatment patterns, clinical outcomes, and healthcare resource utilization is needed to highlight the unmet clinical need and demand for novel therapies within this patient population. Methods: A population-based, retrospective, longitudinal study of adult ES-SCLC patients diagnosed in the province of Alberta, Canada between January 2010 and December 2018 was conducted using provincial electronic medical records and administrative claims data. Results: A total of 1,941 ES-SCLC patients were included of which 1,465 (75%) initially presented with ES-SCLC and 476 (25%) had recurrent disease. Among newly diagnosed ES-SCLC patients, front-line therapy was as follows: 523 (35.7%) chemotherapy and radiotherapy, 280 (19.1%) chemotherapy alone, 133 (9.1%) radiotherapy alone, and 529 (36.1%) best supportive care. The primary sites of radiation were the chest (67.1%) and the brain (45.7%). Median age at diagnosis was 70 years (range: 39-94) and 50.2% were men. In contrast to the de novo patients, the majority of recurrent cases (71.6%) received no front-line therapy. In the full cohort (de novo and recurrent cases), 46.5% of patients initiated first-line, 8.7% second-line, and 1.4% third-line chemotherapy. The majority of patients received either carboplatin plus etoposide (49.5%) or cisplatin plus etoposide (43.0%) in first-line. Median overall survival was higher for patients who were treated with chemotherapy and radiotherapy (10.59 months; 95% CI: 10.03-11.61) compared to patients who received chemotherapy alone (5.65 months; 95% CI: 5.06-6.12), radiotherapy alone (3.02 months; 95% CI: 2.47-4.01), or best supportive care (0.82 months; 95% CI: 0.72-0.92; log-rank p-value < 0.001). Among patients who received first-line systemic therapy, the 1-year, 2-year and 5-year survival was 29.1% (95% CI: 26.3-32.3), 7.3% (95% CI: 5.7-9.2) and 2.9% (95% CI: 1.8-4.5), respectively and the average time spent in hospital was 17, 11, and 10 days per patient within years 1, 2, and 3, respectively. Conclusions: In a Canadian real-world setting, the initiation of first-line treatment in ES-SCLC was low with significant attrition in subsequent lines. It was evident that patients who received treatment had greater survival compared to those who do not. Collectively, these results underscore the need for effective front-line therapeutic options and highlight the potential for novel therapies to improve patient outcomes.

Role of Radiation in Extensive Stage Small Cell Lung Cancer: A National Cancer Database Registry Analysis

The role of prophylactic cranial irradiation (PCI) and thoracic radiation therapy (TRT) in extensive-stage small cell lung cancer remains controversial. The authors examined the National Cancer Database and identified patients with extensive-stage small cell lung cancer with no brain metastasis. Patients were excluded if they died 30 days from diagnosis, did not receive polychemotherapy, had other palliative radiation or had missing information. A propensity score-matched analysis was also performed. A total of 21,019 patients were identified. The majority of patients did not receive radiation (69%), whereas 10% received PCI and 21% received TRT. The addition of PCI and TRT improved median survival and survival at 1 and 2 years (p ≤ 0.05). The propensity score-matched analysis confirmed the same overall survival benefit with both PCI and TRT. This registry-based analysis of >1500 accredited cancer programs shows that PCI and TRT are not commonly utilized for extensive-stage small cell lung cancer patients who are treated with multiagent chemotherapy. The addition of PCI and TRT significantly improves overall survival in this otherwise poor prognostic group. Further research is needed to confirm the role of PCI and TRT, especially in the era of improved systemic therapy.

Prognostic factor analysis of patients with small cell lung cancer: Real-world data from 988 patients.

BackgroundSmall cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking.MethodsPatients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors.ResultsAmong 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC.ConclusionsThe present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively.

60TiP ORIENTAL: An open label, multicenter, phase IIIb study of first-line durvalumab plus platinum-based chemotherapy in Chinese patients with extensive stage small cell lung cancer (ES-SCLC)

60TiP ORIENTAL: An open label, multicenter, phase IIIb study of first-line durvalumab plus platinum-based chemotherapy in Chinese patients with extensive stage small cell lung cancer (ES-SCLC)

FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer.

The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first-line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti-programmed death ligand 1 antibodies when added to platinum-based chemotherapy as compared with chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54-0.91; p = .0069), with median OS of 12.3 months compared with 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR, 0.73; 95% CI, 0.59-0.91; p = .0047) with median OS of 13.0 months compared with 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune-checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents. IMPLICATIONS FOR PRACTICE: Effective therapeutic options for small cell lung cancer (SCLC) are limited, and there has been modest improvement in the overall survival (OS) of patients with SCLC over the past 3 decades. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first-line treatment of patients with extensive stage SCLC represent the first approved therapies with OS benefit for this patient population since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.

Role of thoracic radiation in extensive stage small cell lung cancer: a NCDB analysis.

Prognosis of extensive stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE), is unknown. Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed as independent validation. Univariate, multivariate analyses were conducted with cox proportional hazard model. A P value < 0.05 was considered as statistically significant. A total of 36,762 were analyzed. In both M1a and IPE groups, use of CXRT was significantly associated with younger age, female sex, non-academic institution, and clinical T stage. Both univariate and multivariate analyses showed that use of CXRT demonstrated significantly longer overall survival in all the groups, with lower hazard ratios in M1a and IPE groups than M1b (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of IPE group showed the survival advantage with hazard ratio of 0.54. Use of SEER data validated its survival advantage of CXRT in IPE group. This retrospective database analysis suggests M1a and IPE subgroups have more survival benefit of CXRT than M1b subgroup. Further studies are warranted to confirm the hypothesis.

P50.09 Estimates of First-Line Extensive Stage Small Cell Lung Cancer Treatment Rates from a U.S. Claims Database

Immunotherapy (IO) plus chemotherapy (CT) has been an NCCN-recommended first-line (1L) treatment for extensive stage small cell lung cancer (ES-SCLC) since 2018. Estimates of treated ES-SCLC rates (treated patients per year/real-world population size) are useful in assessing the clinical and economic effects of improved treatments.

P86.07 CDK12 Mutated Extensive Stage Small Cell Lung Cancer Showed an Exceptional Response to Olaparib and Paclitaxel

P86.07 CDK12 Mutated Extensive Stage Small Cell Lung Cancer Showed an Exceptional Response to Olaparib and Paclitaxel

P48.10 Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons

For decades platinum-doublet chemotherapy (CT) has represented the standard of care for extensive stage Small Cell Lung Cancer (ES-SCLC) patients. More recently, the addition of an immune checkpoint inhibitor (ICI) to standard CT has shown to improve survival in patients with treatment-naïve ES-SCLC. The current work aims to assess any difference in both efficacy and safety profiles among different Immuno-Oncology (IO) agents in combination with platinum-based CT in ES-SCLC patients according to different ICIs subtypes. We performed a systematic review (MEDLINE, Cochrane database, meetings abstracts) and finally included in our metanalysis six first-line randomized controlled trials (Reck et al 2013, Reck et al 2016, IMpower 133, EA5161, KEYNOTE-604, CASPIAN) comparing the association of standard CT (carboplatin plus paclitaxel or cisplatin/carboplatin plus etoposide) with an ICI (ipilimumab, nivolumab, pembrolizumab or durvalumab) versus standard CT alone in ES-SCLC. Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), 12-month duration of response rate (DORR), treatment-related adverse events (TRAEs) and discontinuation rates (DRs) were obtained. Although no clear advantage in terms of ORR was directly underlined, our pooled results showed how the addition of ICIs to CT significantly improved DORR (RR 4.45 , 95% CI 1.76 – 11.21), resulting in long term benefits in PFS (HR 0.80, 95% CI 0.73 – 0.86) and OS (HR 0.82, 95% CI 0.75 – 0.90) with no differences in terms of TRAEs or DRs. Of note, indirect comparisons according to the different IO strategies suggested a slight advantage in favor of both PD-1 and PD-L1 over anti-CTLA-4 agents in terms of efficacy outcomes along with no additional significant differences in the safety profile, respectively (Figure 1a-b). When indirectly comparing PD-1 with PD-L1 inhibitors, no relevant significant differences regarding both efficacy and safety endpoints were observed, with benefit trends only for DORR (RR 1.86, 95% CI 0.52 – 6.69) and DR (RR 0.49, 95% CI 0.15 – 1.61) in favor of anti-PD-1 over anti-PD-L1 (Figure 1c). Based on the pooled results of our meta-analysis, the association of an ICI with CT confirmed to provide a survival benefit when compared to CT alone. Although chemo-immunotherapy would now represent an established standard for newly diagnosed ES-SCLC patients, establishing the optimal therapeutic options still addresses an unmet need in the clinical setting and predictive biomarkers eventually need to be identified.

P79.04 A Phase 2 Trial of Nivolumab and Temozolomide in Extensive Stage Small Cell Lung Cancer: Interim Efficacy Analysis.

P79.04 A Phase 2 Trial of Nivolumab and Temozolomide in Extensive Stage Small Cell Lung Cancer: Interim Efficacy Analysis.

P48.18 Chemo-Immunotherapy in First Line Extensive Stage Small Cell Lung Cancer (ES-SCLC): A Systematic Review and Meta-Analysis

Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with early metastatic potential. Standard of care with platinum-etoposide chemotherapy has not changed in 30 years. Immune checkpoint inhibitors (ICI) have recently demonstrated significant improvement in non-small cell lung cancer (NSCLC) patients. There is evidence for increased benefit of ICI in mutagenic cancers, such as SCLC, caused by exposure to carcinogens (i.e. smoking). There are now several studies that report improved progression free survival (PFS) and overall survival (OS) with combined ICI and chemotherapy in ES-SCLC. We aimed to assess the magnitude of the survival benefit of combined chemo-ICI in the first line systemic treatment of ES-SCLC as compared to standard of care chemotherapy. MEDLINE, EMBASE and the Cochrane library were systematically searched, along with abstracts from relevant major conferences (i.e. ASCO, ESMO, WCLC). We searched databases between January 1, 2010 and June 10, 2020 and limited the search of relevant meeting and conference proceedings to 2018 to 2020. Studies were included if they met the following criteria: randomized controlled trials, patients with untreated ES-SCLC treated with combined chemo-ICI as compared to standard of care chemotherapy. Any chemo-ICI pairings were eligible including PD-1 inhibitors, PD-L1 inhibitors and CTLA-4 inhibitors, combined with platinum-etoposide or platinum-paclitaxel chemotherapy. Trials were excluded if patients were being treated in the second or further line. Relevant outcomes of interest were survival outcomes (PFS and OS), measures of response (objective response rate (ORR), duration of response (DoR)), and toxicity (Grade 1-4 toxicity, Grade 3-4 toxicity). A total of 2705 studies and abstracts were identified in our initial search, with 6 studies (33 publications) included in the final analysis. PFS was significantly improved for patients randomized to chemo-ICI compared with chemotherapy alone (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.75-0.87). Similarly, OS was significantly improved (HR 0.82, 95% CI 0.76-0.89). The between-study heterogeneity was low (I2 0%) for both outcomes. A prespecified subgroup analysis demonstrated no evidence of any significant differential effect between PD-1/PD-L1 inhibitors and CTLA-4 inhibitors. The pooled ORR as expressed as a risk ratio comparing chemo-ICI with chemotherapy alone was 1.04 (95% CI 0.98-1.10) and the pooled duration of response demonstrated a mean difference of 0.09 months (95% CI -0.13-0.32) in favor of chemo-ICI. There were no significant increases in either all grade adverse events (pooled risk ratio of 1.03, 95% CI 1.01-1.06), or grade 3-4 adverse events (risk ratio of 1.06, 95% CI 0.99-1.13). Multiple trials have assessed the efficacy of combined chemo-ICI regimens. They consistently demonstrate survival improvements in both PFS and OS with combined chemo-ICI. This review demonstrates an approximate18% risk reduction in death, and 19% risk reduction in disease progression. The pooled analysis suggests a minimal increase in toxicity with chemo-ICI regimens though clinically relevant toxicity (Grade 3-4 toxicity) crossed null. Chemo-ICI appears to offer survival benefit with potentially equivalent toxicity profile in the setting of first line ES-SCLC regardless of the class of ICI.

P50.01 A Year Experience With Atezolizumab Plus Chemotherapy For Small Cell Lung Cancer In Alberta, Canada

The authors assessed the real-world effectiveness of newly approved regimen, atezolizumab plus carboplatin-etoposide (Atezo-CaE) for extensive stage (ES) small cell lung cancer (SCLC) in Alberta, Canada. Atezo-CaE is yet to be provincially funded for ES treatment but can be accessed through special access programs. Included in this study were confirmed ES patients treated with first-line Atezo-CaE at the tertiary and community cancer care centres in Alberta, Canada post FDA/ Health Canada approval (2019) up to the data cut-off date (September 1, 2020). Demographic and clinical data were extracted from the institutional Glans-Look Research Database. Any with active multiple malignancies and/or prior curative-intent treatment were excluded. Outcomes including overall response rate (ORR, RECIST v1.1), adverse events (CTCAE criteria v5), progression-free and overall survival were estimated using descriptive and Kaplan-Meier survival (Log-Rank) statistics. A priori statistical significance was p < 0.05. Analyses were performed using SPSS statistical software (version 25). There were 34 patients seen at the community care centres (18%) or academic tertiary institutions (82%). 53% were male, 24% had ECOG performance status ≥2 and the median age was 65 years. The median number of days from diagnosis to Atezo-CaE receipt was 40 (range: 14-128) days. 21% had no maintenance atezolizumab. In addition, 65% had radiotherapy treatment. 21% were still having ongoing atezolizumab treatment. The median duration of atezolizumab was 4.2 (range: 0.1-13.5) months. ORR was 62% with a median of 84 (range: 47-210) days time to best response. 18% have an ongoing response to atezolizumab. Disease progression was the commonest reason for 1L discontinuation while also accounting for the 2nd most common reason for no maintenance atezolizumab only after adverse events. Overall, progressive disease rate was 76%. The median duration of response was 98 (range: 35-635) days. 24% continued atezolizumab for ≥ 1 month past disease progression. 2L rate was 26%. The median progression-free and overall survival for all patients were 6 (95% CI: 4-8) and 11 (95% CI: 9-11) months while in those who received maintenance atezolizumab were 8 (p=0.01) and 13 (p<0.01) months respectively. Within a year of Atezo-CaE treatment for ES, there was 18% ongoing response to Atezo-CaE. The ORR (62 vs 60%), median treatment duration (4.2 vs 4.7 months) and overall survival outcomes (12.7 vs 12.3 months) appeared consistent in real-world versus clinical trial patients1. Future study to identify factors predicting Atezo-CaE treatment response and survival outcomes in SCLC is very much needed.

Role of thoracic radiotherapy in extensive stage small cell lung cancer: a systemic review and meta-analysis.

BackgroundThe role of thoracic consolidation radiotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) remains controversial. This study aimed to evaluate the efficacy of thoracic radiotherapy (TRT) in these patients.MethodsA systematic literature search was performed in PubMed, Embase, and the Cochrane library to identify qualified clinical studies. The hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS) and local recurrence-free survival (LRFS) were extracted, and toxicity of the TRT group versus non-TRT group was analyzed.ResultsA total of 12 studies were included in this meta-analysis, including 936 patients in the TRT group and 1,059 patients in the non-TRT group. The combined results showed that TRT significantly improved OS (HR =0.65; 95% CI: 0.55–0.77, P<0.00001), PFS (HR =0.64; 95% CI: 0.56–0.72, P<0.00001) and LRFS (HR =0.38, 95% CI: 0.26–0.53, P<0.00001). Subgroup analysis showed that OS benefits were observed in patients receiving sequential TRT (HR =0.67; 95% CI: 0.54–0.84, P=0.0006). The addition of TRT significantly improved OS in patients over 65 years of age (HR =0.55; 95% CI: 0.40–0.74, P=0.0001). For patients with only one organ metastasis, there was no significant difference in OS between the two groups (HR =0.61; 95% CI: 0.36–1.01, P=0.06). There was no statistical difference in hematologic toxicity (leukopenia, thrombocytopenia, anemia) and non-hematologic toxicity (nausea or vomiting) between the two groups. The incidence of grade ≥3 esophageal toxicity was 4.6% in the TRT group and 0% in the non-TRT group (P=0.0001). Grade ≥3 bronchopulmonary toxicity was 2.9% in the TRT group and 0.8% in the non-TRT group (P=0.02).ConclusionsTRT improves OS, PFS and LRFS in patients with ES-SCLC, with a low increase in esophageal and bronchopulmonary toxicity. More randomized controlled trials (RCTs) are expected to confirm our conclusions.PROSPERO registration numberCRD42020190575.

Generalized and orofacial choreoathetosis: a case report of anti-CV2 paraneoplastic syndrome after cardiac arrest

ABSTRACT CV2/CRMP5 is the most common antibody accompaniment of paraneoplastic choreoathetosis. We present a case of paraneoplastic choreothetosis with associated cerebellar dysfunction, peripheral neuropathy, and likely dysautonomia. Our patient developed a movement disorder after a cardiopulmonary arrest, which unfortunately masked the true etiology of his symptoms. He was later found to have extensive stage small cell lung cancer, with further evaluation revealing seropositivity for anti-CV2 antibodies. Choreoathetosis is a known sequelae of hypoxic-ischemic brain injury, but clinicians should continue to keep an open mind. The utility of immunotherapy is unclear in these circumstances and many physicians adopt a symptom-based approach.

394P Apatinib plus etoposide capsules as third-line or further-line treatment for extensive stage small cell lung cancer patients: A multicenter, single arm, phase II clinical trial

394P Apatinib plus etoposide capsules as third-line or further-line treatment for extensive stage small cell lung cancer patients: A multicenter, single arm, phase II clinical trial

Utilization of Prophylactic Cranial Irradiation for Extensive Stage Small Cell Lung Cancer–Is There a Benefit in the MRI Screening Era?

Utilization of Prophylactic Cranial Irradiation for Extensive Stage Small Cell Lung Cancer–Is There a Benefit in the MRI Screening Era?

Outcomes of Initial Therapy for Synchronous Brain Metastases from Extensive Stage Small Cell Lung Cancer

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. 20% of SCLC patients have synchronous brain metastases at initial diagnosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases treated with chemotherapy (chemo) and/or whole brain radiation (WBRT). Among the 836 SCLC patients treated at a single institution between 1998 and 2018, 109 patients with synchronous brain metastases at initial diagnosis were included in this retrospective analysis. Survival was estimated with the Kaplan-Meier method. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression modeling and log-rank testing. Of the 109 patients, 18 received chemo without WBRT, 15 received WBRT without chemo, and 76 received chemo and WBRT. Of the 76 patients who received chemo and WBRT, 8 started both concurrently, 35 received chemo first, and 33 received WBRT first. Median WBRT dose was 30 Gy in 10 fractions. The median number of brain lesions at diagnosis was 3, and the median size of the largest metastasis was 2.0 cm. Median OS for the entire cohort was 9 months and median bPFS was 8.4 months. OS was 30.3% at 1 year and 14.4% at 2 years. Increased number of brain lesions was significantly associated with decreased OS. 59 patients presented with neurological symptoms, which was not associated with OS or bPFS. 46 patients had isolated brain metastases (no extracranial metastases), which was not associated with improved OS (p = 0.061) or bPFS (p = 0.17) compared to patients with other extracranial metastatic disease. The median age at diagnosis was 63. Patients younger than 63 years old had improved OS compared to patients age 63 or older, but not bPFS. Patients who received chemo and WBRT had improved OS compared to those who had either chemo or WBRT alone (p<0.001), but there was no difference in bPFS (p = 0.34). There was no significant difference in OS or bPFS depending on the sequence of therapy initiation. For patients who had chemo followed by WBRT, the median time between start of chemo and start of radiation was 103 days (range 6 – 182 days), which was not significantly associated with OS or bPFS. 13 patients received upfront brain metastasis resection, which was associated with improved OS but not bPFS compared to those who did not have surgery. 14 patients received SRS or partial brain radiation as part of their initial therapy, which was not significantly associated with OS or bPFS. 15 patients received salvage brain radiation after WBRT failure, which was associated with improved OS compared to those who did not have salvage radiation (25.5 months vs 8.0 months, p<0.001). The combination of chemo and WBRT was associated with improved OS compared to either modality alone. The sequence of treatment was not associated with OS or bPFS. Shorter time to WBRT after chemo was not significantly associated with OS or bPFS.