Extensive Disease Small Cell Lung Research Articles

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

Study design and rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease small cell lung cancer

BackgroundStudies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide. MethodsWe initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety. ResultsThis study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer. Clinical trial registrationEU CT: 2023-504670-38-00.

Sintilimab plus anlotinib as second or further-line therapy for extensive disease small cell lung cancer: a phase 2 investigator-initiated non-randomized controlled trial

Treatment options remain rather limited for extensive disease small cell lung cancer (ED-SCLC) patients in second or further-line setting. The phase 2 investigator-initiated non-randomized study enrolled patients who had disease progression on at least one line of platinum-based chemotherapy. Participants received intravenous sintilimab 200mg on day one and oral daily anlotinib 12mg on days 1-14 once every three weeks per cycle. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. This study is registered with ClinicalTrials.gov (NCT04055792). Forty-two patients were enrolled between August 29, 2019 and December 26, 2021at Henan Cancer Hospital in China. 37 patients were evaluable for efficacy. The median follow-up was 24.8 months (IQR: 16.9-28.2). The median PFS was 6.1 months (95% CI: 5.0-7.3). The OS was 12.7 months (95% CI: 7.1-18.2). The ORR was 56.8% (21/37, 95% CI: 40.0-73.5) and the DCR was 89.2% (33/37, 95% CI: 78.7-99.7). Forty patients (40/42, 95%) had at least one treatment-related adverse event (TRAE). Immune-related adverse events (irAEs) were reported in 39 patients (39/42, 93%), while grade 3 or higher irAEs occurred in 11 patients (11/42, 26%). The most frequent irAEs were hypothyroidism (16/42, 38%), elevated gamma-glutamyl transpeptidase (15/42, 36%) and elevated creatine kinase MB (15/42, 36%). The most frequent grade 3 or higher irAEs were elevated gamma-glutamyl transpeptidase (5/42, 12%) and increased aspartate aminotransferase (3/42, 7%). Sintilimab plus anlotinib demonstrated promising antitumor activities as second or further-line therapy for ED-SCLC and had manageable toxicities. The findings support further randomized controlled trials of this combination regimen for ED-SCLC. Henan Province Health and Youth Subject Leader Training Project, Henan Health Science and Technology Innovation Talents, ZHONGYUAN QIANREN JIHUA, Henan International Joint Laboratory of drug resistance and reversal of targeted therapy for lung cancer, Tumor Research Fund of Anti-Angiogenesis Targeted Therapy of China Anti-Cancer Association.

Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer.

Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.

Relationship between patterns of immunohistochemical conventional neuroendocrine markers and efficacy of immune check point inhibitors in patients with extensive disease small cell lung cancer.

Which patients benefit from the addition of immune checkpoint inhibitors (ICIs) to chemotherapy for small cell lung cancer (SCLC) remains unclear. There have been few reports on the efficacy of ICIs based on conventional immunohistochemical neuroendocrine (NE) markers (synaptophysin, chromogranin A, and neural cell adhesion molecule [NCAM]). In the present study, we aimed to analyze the relationship between the expression of immunohistochemical NE markers and the efficacy of ICIs in patients with extensive disease (ED)-SCLC, to assess whether conventional NE markers are predictive of ICIs. Patients with untreated ED-SCLC who received first-line therapy at the Shizuoka Cancer Center between November 2002 and July 2021 were retrospectively reviewed. We evaluated the efficacy of first-line chemotherapy according to the expression status of each immunohistochemical NE marker in patients treated with ICI plus chemotherapy (ICI-chemo group) and with chemotherapy alone (chemo group). A total of 227 patients were included in the ICI-chemo and chemo groups, respectively. The progression-free survival (PFS) tended to be better in patients in the ICI-chemo group than those treated with chemotherapy alone in patients with NE marker-positive SCLC. In particular, it was statistically significant in patients with chromogranin A-positive SCLC (p = 0.036). In patients with NE marker-negative SCLC, no significant differences were observed in PFS between the two groups. There were no significant differences in overall survival (OS), regardless of the expression of any conventional NE marker. Our study suggests that the efficacy of ICIs in addition to chemotherapy may be poor in patients with NE marker-negative SCLC.

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1months; HR: 0.52; p = 0.0127). Patients older than 70years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

2008P Brazilian real-world data of immunotherapy (IO) in extensive disease small cell lung cancer (ES-SCLC)

2008P Brazilian real-world data of immunotherapy (IO) in extensive disease small cell lung cancer (ES-SCLC)

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Consolidative thoracic radiotherapy for extensive disease small cell lung cancer

Relationship between immune-related adverse events and treatment effectiveness in extensive disease small cell lung cancer.

This study aimed to assess the relationship between immune response adverse events (irAEs) and treatment efficacy in patients with extensive disease small cell lung cancer (ED-SCLC). We retrospectively evaluated the clinical effects in 40 ED-SCLC patients who had received immune-checkpoint inhibitors (ICIs), platinum agents, and etoposide between September 2019 and September 2021. We identified and compared patients belonging to two groups: irAE and non-irAE. Fifteen patients experienced irAEs, and 25 did not. The median progression-free survival in patients with irAE was longer than that in patients without irAE (12.6 months [95% CI: 6.3-19.3 months] vs. 7.2 months [95% CI: 5.8-7.9 months], p = 0.0108). However, the median overall survival (OS) was similar between irAE and non-irAE groups (27.6 months [95% CI: 15.4-NA] vs. 24.9 months [95% CI: 13.7-NA], p = 0.268). Seven (46.7%) in the irAE group and 20 (80%) in the non-irAE group received sequential therapy. The median OS was prolonged in patients who received first- and second-line therapy than in those who received first-line therapy alone (27.6 months [95% CI: 19.2-NA] vs. 6.6 months [95% CI: 0.3-NA], p = 0.053). Grade ≧ 3 irAEs occurred in five (12.5%) patients. Among them, grade 5 irAEs were observed in two patients, including exacerbation of polymyositis and pulmonary arterial embolism. In this study, the development of irAEs did not affect OS in patients with ED-SCLC who received platinum-based agents, etoposide, or ICI therapy. We determined that managing irAEs and administering first- and second-line therapies could contribute to prolonged OS.

Post-progression survival after atezolizumab plus carboplatin and etoposide as first-line chemotherapy in small cell lung cancer has a significant impact on overall survival.

BackgroundThe effect of first‐line chemotherapy on overall survival (OS) may be significantly influenced by subsequent therapy for patients with extensive disease small cell lung cancer (ED‐SCLC). Therefore, we evaluated the relationship between progression‐free survival (PFS), post‐progression survival (PPS), and OS of ED‐SCLC patients treated with atezolizumab plus carboplatin and etoposide as first‐line therapy.MethodsWe analyzed the data of 57 patients with relapsed ED‐SCLC treated with atezolizumab plus carboplatin and etoposide (AteCE) as first‐line chemotherapy between August 2019 and September 2020. The respective correlations between PFS‐OS and PPS‐OS following first‐line AteCE treatment were examined at the individual patient level.ResultsSpearman's rank correlation analysis and linear regression analysis showed that PPS strongly correlated with OS (r = 0.93, p < 0.05, R 2 = 0.85) and that PFS moderately correlated with OS (r = 0.55, p < 0.05, R 2 = 0.28). Performance status at relapse (0–1/≥2), number of cycles of atezolizumab maintenance therapy (<3/≥3), and platinum rechallenge chemotherapy all significantly positively correlated with PPS (p < 0.05).ConclusionsUpon comparing OS‐PFS and OS‐PPS in this patient population, OS and PPS were found to have a stronger correlation. These results suggest that performance status at relapse, atezolizumab maintenance, or chemotherapy rechallenge could affect PPS.

1540P Real-world analysis of outcomes of first-line chemo-immunotherapy in patients with extensive disease small cell lung cancer (ED-SCLC)

SCLC accounts for approximately 13% of lung cancer diagnoses. For the more than 70% of patients diagnosed with ED-SCLC the standard of care 1L-treatment is platinum and etoposide in combination with PD-L1 blockade, based on the 2-month improvement in median overall survival (OS) in two randomized phase III trials. Yet, the efficacy and safety of first-line chemo-immunotherapy in patients with ED-SCLC in a real-world setting remains unclear. Patients with ED-SCLC who received first-line ICI in combination with platinum-based chemotherapy at ten cancer centers in Switzerland were included in this retrospective analysis. Responses were assessed by the local investigators using standard RECIST v1.1 criteria. Progression-free survival (PFS) and OS were analyzed by the Kaplan-Meier method. 200 patients were included between October 2018 and October 2021. Mean age was 67 years, 117 (58.5%) were males, 125 patients (62.5%) were current and 68 (34.0%) former smokers. 39 patients (25.3%) had a performance status (PS) ≥2. 185 patients (92.5%) were diagnosed with ED-SCLC, 15 patients (7.5%) had a relapse after initial limited disease stage treatment. The majority of patients was treated with atezolizumab (n=190, 95.5%) in combination with chemotherapy, 4.5% received durvalumab. 69 patients (35.2%) had undergone radiotherapy (RT) prior to or during ICI. At the time of analysis, 132 patients (66.0%) have died. Median duration of response was 2.6 months. Median PFS and OS were 6.1 and 11.0 months, respectively. The overall response rate was 75.2%. Immune-related adverse events were seen in 25.0% of patients with no new safety signals. Most frequent sites of tumor progression were lung (21.5%), lymph nodes (19.5%) and brain (15.4%). 112 patients (56.6%) received another systemic therapy after combined chemo-immunotherapy. This is the largest retrospective analysis of outcomes of 1L chemo-immunotherapy in patients with ED-SCLC in the real-world setting also including patients with ECOG PS ≥2. Outcomes in this real-world cohort are comparable to data in the pivotal trials. It will be important to better characterize the patient population that benefits most from this treatment strategy.

New Advances in Supportive Care: Chemoprotective Agents as Novel Opportunities in Geriatric Oncology.

To explore the effectiveness of trilaciclib and ALRN-6924 in the prevention of cancer chemotherapy-induced toxicity in older patients. New chemoprotective agents are necessary because age is the main risk factor for chemotherapy complications that account largely for the poorer outcome of cancer in the elderly. Trilaciclib and ALRN-6924 cause a reversible block of the proliferation of normal cells through cell cycle arrest (CCA). With this mechanism, they may prevent the toxicity of cycle-active cancer treatment including neutropenia, anemia, thrombocytopenia, lymphopenia, mucositis, and alopecia. Myelopoietic growth factors may prevent neutropenia in the aged, but they may cause severe bone pain, may aggravate thrombocytopenia and anemia, and may cause myelodysplasia and acute leukemia as a late complication. The prevention of thrombocytopenia, anemia, mucositis, and alopecia is unsatisfactory at present. These complications may jeopardize the treatment outcome as they require a reduction of treatment dose/intensity and because many patients find the resulting symptoms intolerable. In three studies of patients with extensive disease small cell lung cancer (ES-SCLC), trilaciclib reduced the severity and duration of neutropenia and thrombocytopenia as well as the need for blood transfusions. In addition, it produced a significant expansion of T-cell clones. Trilaciclib received FDA approval for the prevention of chemotherapy-induced myelosuppression in patients with ES-SCLC. ALRN-6924 is currently studied in phase II study of ES-SCLC. In a phase IB of 38 patients, ALRN-6924 prevented myelosuppression to an extent comparable with trilaciclib. Both drugs proved as effective in patients 65 and older as they were in the younger ones. In an "ex vivo" study, ALRN-6924 protected the epithelial stem cells of hair follicles from taxanes and promised to prevent alopecia. The possibility that CCA of tumor cells may reduce the effectiveness of cycle-active chemotherapy is a major concern. For this reason, the use of trilaciclib, an inhibitor of CDK 4/6, should be limited to tumors with inactivated RB1, and the use of ALRN-6924, an inhibitor of P53, should be limited to tumors with inactivated P53. Chemotherapy-related toxicities limit dose intensity and contribute to significant morbidity and mortality in elderly cancer patients. Trilaciclib and ALRN-6924 are of particular interest to geriatric oncologists because of their novel mechanism of action. Ameliorating chemotherapy-induced toxicities holds the promise of transforming the practice of geriatric oncology by enabling chemotherapeutic regimens that are currently not feasible for this patient population. Specifically, these agents may prevent chemotherapy-induced neutropenia and thrombocytopenia, perhaps the most life-threatening complications of cytotoxic chemotherapy, thereby obviating the need for the use of rescue strategies such as hematopoietic growth factors. In addition, these agents offer the potential for broad tissue protection from other chemotherapy-related toxicities, including mucositis, diarrhea, and alopecia, which historically have been poorly managed. Importantly, by preventing a spectrum of chemotherapy-related toxicities, these agents may permit the administration of chemotherapy at full-dose intensity, prevent functional decline, and grant maintenance of resilience to older cancer patients. As a result, the successful prevention of chemotherapy-induced side effects may not only mitigate the costs of care but also improve patient outcomes and quality of life. Finally, chemoprotective strategies offer the opportunity to apply geriatric principles to clinical trials of cancer treatment. In particular, they may allow the testing of prolongation of "active life expectancy" as a major goal of clinical trials in elderly patients. They may also enable novel and more practical forms of clinical trials. By assessing the risk of chemotherapy-related toxicity with the Chemotherapy Risk Assessment Scale for High Age Patients (CRASH) or the Cancer and Aging Research Group (CARG) instruments, these agents may permit researchers to utilize patients as their own controls and endorse the approval of supportive care drugs based upon the risk profile of individual patients.

Long-term outcomes in extensive disease small cell lung cancer patients treated without immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been approved as first-line treatment for patients with untreated extensive disease-small cell lung cancer (ED-SCLC). However, there are few reports about the long-term outcomes in patients with ED-SCLC treated without ICIs. Thus, we analyzed the long-term outcomes in patients with ED-SCLC. We retrospectively examined the medical records of patients with SCLC who were treated at our hospital between September 2002 and September 2019. The main inclusion criteria were as follows: (i) histological or cytological confirmation of SCLC, (ii) diagnosed with ED-SCLC and (iii) received chemotherapy, not including ICIs, as the first-line treatment. To assess the trends of treatment outcomes, we compared the survival outcomes between 2002-2010 (early) and 2011-2019 (late) groups. A total of 314 patients were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69years; 82% of the patients were male and 70% had a performance status of 0 or 1. The median follow-up time of overall survival (OS) was 7.4years, and 89% of the patients died. The median progression-free survival and survival time were 4.9 and 12.1months, respectively. Five-year survival rate was 2%. There was no significant difference in survival between the early and late groups. We found that the long-term outcomes in ED-SCLC patients treated without ICIs were poor. Prior to the approval of ICI treatment for ED-SCLC, there was no improvement in the OS for ~20years.

P30-3 Clinical experience of tumour lysis syndrome in patients with extensive disease small cell lung cancer

P30-3 Clinical experience of tumour lysis syndrome in patients with extensive disease small cell lung cancer

History of Extensive Disease Small Cell Lung Cancer Treatment: Time to Raise the Bar? A Review of the Literature.

Simple SummarySmall cell lung cancer (SCLC) remains the most aggressive form of neuroendocrine tumor of the lung, for which treatment options remain limited. The introduction of immune checkpoint inhibitors has modified for the first time the therapeutic strategies in patients with extensive disease after decades. New therapeutic approaches are required. Deeper knowledge of tumor biology is required to gain new insights into this complex disease.Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.

Systematic evaluation of the efficacy-effectiveness gap of systemic treatments in extensive disease small cell lung cancer.

The aim of this study is to assess how clinical outcomes in real-world (effectiveness) correspond to the outcomes in clinical trials (efficacy) of systemic treatments for extensive disease small cell lung cancer (ED SCLC). All patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. For every patient, an efficacy-effectiveness factor (EE factor) was calculated by dividing individual patients' overall survival (OS) by the pooled median OS assessed from clinical trials with the respective treatment. From 792 diagnosed patients, 568 (72%) started with first-line treatment. Overall, the median EE factor was 0.79 (P < .001 from 1.00). Poor performance status (ECOG≥2) and a higher age at diagnosis (age ≥ 65 years) were independent predictors for a lower EE factor. The EE gap was 43% in patients with both age ≥ 65 years and ECOG ≥2 (EE factor 0.57). The mean age and the proportion of patients with ECOG≥2 in real-world were different from those in clinical trials (mean age of 66 versus 62 years, and ECOG≥2 25% versus 17%; both P < .001). OS of patients with ED SCLC treated with systemic therapy in real-world practice is 21% shorter than for patients included in trials. Age at diagnosis and performance status partly explain this gap.

LBA85 REACTION: A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer

Anti-PD-L1 antibodies extend overall survival (OS) of patients with extensive disease Small Cell Lung Cancer (ED-SCLC) when combined with platinum-etoposide (Pl-E) from cycle 1. We evaluated the benefit of first-line pembrolizumab (P) combined with Pl-E from cycle 3 in the subgroup of chemo-sensitive ED-SCLC.

Artificial intelligence and lung cancer treatment decision: agreement with recommendation of multidisciplinary tumor board.

BackgroundIBM Watson for Oncology (WFO) is a cognitive computing system helping physicians quickly identify key information in a patient’s medical record, surface relevant evidence, and explore treatment options. This study assessed the possibility of using WFO for clinical treatment in lung cancer patients.MethodsWe evaluated the level of agreement between WFO and multidisciplinary team (MDT) for lung cancer. From January to December 2018, newly diagnosed lung cancer cases in Chonnam National University Hwasun Hospital were retrospectively examined using WFO version 18.4 according to four treatment categories (surgery, radiotherapy, chemoradiotherapy, and palliative care). Treatment recommendations were considered concordant if the MDT recommendations were designated ‘recommended’ by WFO. Concordance between MDT and WFO was analyzed by Cohen’s kappa value.ResultsIn total, 405 (male 340, female 65) cases with different histology (adenocarcinoma 157, squamous cell carcinoma 132, small cell carcinoma 94, others 22 cases) were enrolled. Concordance between MDT and WFO occurred in 92.4% (k=0.881, P<0.001) of all cases, and concordance differed according to clinical stages. The strength of agreement was very good in stage IV non-small cell lung carcinoma (NSCLC) (100%, k=1.000) and extensive disease small cell lung carcinoma (SCLC) (100%, k=1.000). In stage I NSCLC, the agreement strength was good (92.4%, k=0.855). The concordance was moderate in stage III NSCLC (80.8%, k=0.622) and relatively low in stage II NSCLC (83.3%, k=0.556) and limited disease SCLC (84.6%, k=0.435). There were discordant cases in surgery (7/57, 12.3%), radiotherapy (2/12, 16.7%), and chemoradiotherapy (15/129, 11.6%), but no discordance in metastatic disease patients.ConclusionsTreatment recommendations made by WFO and MDT were highly concordant for lung cancer cases especially in metastatic stage. However, WFO was just an assisting tool in stage I–III NSCLC and limited disease SCLC; so, patient-doctor relationship and shared decision making may be more important in this stage.

Real‐world treatment patterns and outcomes of patients with extensive disease small cell lung cancer

ObjectiveClinical outcome data on patients with extensive disease small cell lung cancer (ED SCLC) treated in routine practice is limited. The aim of this retrospective study is to present data on treatment patterns and survival in an unselected patient population with ED SCLC.MethodsAll patients diagnosed with ED SCLC between 2008 and 2014 in six Dutch large teaching hospitals (Santeon network) were included. We collected data on patient characteristics, systemic treatments, overall survival (OS), dose reductions (<80% of initial dose) and early discontinuation (<4 cycles).ResultsFrom 792 diagnosed patients, 568 (72%) started with first‐line treatment. Of these patients, 41% received second‐line treatment. Only 68 patients received third‐line treatment. For all treated patients, the mean age was 66 years. The majority (72%) had a performance status (ECOG) of 0 or 1 at diagnosis. Median OS of treated patients was 7.4 months. Of all patients with first‐line treatment, 26% received <4 cycles and dose reductions were observed in 29%.ConclusionAfter first‐line systemic treatment in ED SCLC the fraction of patients receiving subsequent lines of treatment is rapidly decreasing. This information is necessary as background for evaluation of the added value of future drugs under study for ED SCLC.

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

PurposeTo identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methodsAmong 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. ResultsMedian follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). ConclusionThree prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended.