Timing of chemotherapy in small cell lung cancer: A National Cancer Database analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20076-e20076
Author(s):  
Shruti Bhandari ◽  
Danh Pham ◽  
Rohit Kumar ◽  
Jeremy T Gaskins ◽  
Goetz H. Kloecker
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Univariate Analysis ◽  
Small Cell ◽  
National Cancer Database ◽  
Small Cell Lung ◽  
Cytotoxic Treatment ◽  
Significant Difference

e20076 Background: Small cell lung cancer (SCLC) is an aggressive disease currently treated as soon as possible given its rapid doubling time. Evidence for appropriate timing of chemotherapy from diagnosis (TCD) for SCLC is lacking. This study evaluates TCD in SCLC on a national level. Methods: National Cancer Database identified SCLC patients treated with chemotherapy from 2010 - 2014. Factors associated with TCD were identified with multiple linear regression analyses. TCD was categorized into four groups using cutoff points of 7, 14, and 28 days. Using these categories, median overall survival (MOS) and log-rank test was used for univariate analysis of the survival outcome and the Cox model for multivariate analysis. Results: Among the 64491 SCLC, 42% received chemotherapy alone, 38% chemotherapy followed by radiation and 20% radiation followed by chemotherapy. Median TCD is 14 days with 21% treated within 7d, 21% 8-14d, 30% 15-28d and 28% > 28d from diagnosis. Age, race, insurance, comorbidities and stage were associated with TCD (Table). Significant difference in survival was found by TCD categories (P < .001). MOS for TCD within 7d was 8.2m, 8-14d was 9.2m, 15-28d was 10.3m, and > 28d was 10.8m. In the multivariate analysis, increased TCD was associated with better survival across all stages. Among stage IV patients, compared to those treated within 1 week, the HR is 0.92 (P < .001) for 1-2 weeks, HR 0.82 (P < .001) for 2-4 weeks, and HR 0.77 (P < .001) for > 4 weeks. Results are similar for Stage III and for Stage I/II. Conclusions: These results show a trend towards poor survival with early treatment. While we do not suggest delaying treatment for SCLC patients, our results provide new evidence to inform a discussion about appropriate treatment timing and individualizing treatment. Optimization of patients' clinical baseline before hasty cytotoxic treatment may lead to better outcomes. [Table: see text]

scholarly journals Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2800
Author(s):  
Amir Onn ◽  
Teodor Gottfried ◽  
Amos Stemmer ◽  
Sarit Appel ◽  
Yaacov R. Lawrence ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
The Impact

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.

scholarly journals Development and Validation of Nomograms for Predicting Survival of Elderly Patients With Stage I Small-cell Lung Cancer

2020 ◽  
Author(s):  
Yaji Yang ◽  
Shusen Sun ◽  
Feng Xiong ◽  
Yin Xiao ◽  
Jing Huang
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Univariate Analysis ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Predictive Tool

Abstract Background Predictive models to determine the prognosis of elderly patients with Stage I small-cell lung cancer (SCLC) are lacking. This study aimed to establish a useful nomogram for predicting the cancer-specific survival (CSS) of elderly patients with Stage I SCLC.MethodsUsing the Surveillance, Epidemiology, and End Results registry database, we identified patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014. The CSS was evaluated by the Kaplan-Meier method. Patients were divided into training and validation cohorts. In the training cohort, univariate analysis and multivariate analysis by the Cox proportional hazards regression identified risk factors that predicted CSS and the results were used to formulate a nomogram for the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The performance of the nomograms was internally and externally validated by the bootstrap resampling.Results: In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41 months. Multivariate analysis revealed that age, histologic type, tumor size, and AJCC Stage were significant predictors of CSS. A nomogram was formulated based on the results of multivariate analysis. The C-indices of the nomogram for training and validation cohorts were 0.68 and 0.62, indicating that the nomogram exhibited a sufficient level of discrimination. The calibration curves demonstrated good agreement between the nomogram prediction and actual observation.Conclusion:A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patient counseling and treatment decision making.

Gender and health care outcomes in patients with non-small cell lung cancer: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18113-e18113
Author(s):  
Junior S Torres-Roman ◽  
Claudio J. Flores ◽  
Alfredo Aguilar ◽  
Denisse Bretel ◽  
Christian Diego Rolfo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Univariate Analysis ◽  
Small Cell ◽  
Healthcare Outcomes ◽  
Small Cell Lung ◽  
Statistical Heterogeneity

e18113 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It is well known that there are differences in the outcome between genders; however the effects of the sex in the prognosis have not been previously properly defined. Our aim was to evaluate in a meta-analysis, differences in healthcare outcomes between women and men with NSCLC in terms of overall survival (OS) and progression-free survival (PFS). Methods: We searched for references of published studies of hospitalary databases indexed in PubMed/Medline. We retrieved 67 references (from 1989 to 2016), of which eleven references were eligible for data extraction. In total, 11 references were evaluable for OS. Meta-analysis for Hazard Ratios (HR) obtained from univariate and multivariate analysis were analyzed in different groups. The meta-analysis was done in the software Review Manager 5.3. Results: In total, 7 studies had information for OS univariate analysis, 7 studies for OS multivariate analysis, only, one for PFS univariate analysis and one for PFS multivariate analysis. The meta-analysis for OS univariate analysis resulted in a HR = 0.75 (P < 0.00001; 95% CI: 0.71 to 0.79) for women compared to men, although there was a high statistical heterogeneity between cohorts (P < 0.0001). In the meta-analysis for OS multivariate analysis was estimated a HR = 0.75 (P < 0.00001; 95% CI: 0.73 to 0.78), with statistical heterogeneity between cohorts (P = 0.0005). Conclusions: Our study quantified a 25%-risk reduction of death for women with NSCLC compare with male men patients with the same diagnosis.

scholarly journals Differential Expression of PD-L1 in Central and Peripheral and TTF1-Positive and -Negative Small-Cell Lung Cancer

2021 ◽  
Vol 7 ◽  
Author(s):  
Shili Yu ◽  
Meng Jia ◽  
Yuemin Li ◽  
Ping-Li Sun ◽  
Hongwen Gao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Differential Expression ◽  
Cell Lung Cancer ◽  
Survival Data ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Central Type ◽  
Significant Difference

Background: Central and peripheral location as well as thyroid transcription factor-I (TTF-1) expression was reported to be associated with different characteristics and prognosis of small-cell lung cancer (SCLC). This study aimed to investigate differential expression of PD-L1 in different SCLC subtypes, and in biopsy and resection specimens.Methods: We retrospectively analyzed 142 SCLC tumor samples using immunohistochemistry to correlate PD-L1 (22C3) expression with clinicopathologic features and survival data.Results: PD-L1 expression was found in 19.7% SCLCs (28/142) and was more frequent in females than in males (32%, 16/50 vs. 13%, 12/92, p = 0.009), in central type than in peripheral type SCLCs (26%, 26/100 vs. 4.8%, 2/42, p = 0.003), and in TTF-1 positive than in negative SCLCs (23.8%, 25/105 vs. 8.1%, 3/37, p = 0.039). PD-L1 expression was associated with vascular (p = 0.001) and lymphatic invasion (p = 0.001). There was no significant difference in PD-L1 expression between biopsy and resection specimens. On univariate analysis, patients with PD-L1 expression had significantly shorter progression-free survival (PFS; p = 0.026) and overall survival (OS; p = 0.012). Multivariate analysis revealed that PD-L1 expression was an independent prognostic factor for OS (HR, 2.317; 95% CI 1.199–4.478; p = 0.012) and PFS (HR, 1.636; 95% CI 0.990–2.703; p = 0.051) in SCLC.Conclusions: PD-L1 expression was more frequent in central type, TTF-1 positive SCLCs, and predicted a poor clinical outcome in these patients. Therefore, tumor location and TTF-1 expression could predict expression status of PD-L1, and could potentially serve as clinical response to immunotherapy.

scholarly journals Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer and Interstitial Lung Abnormalities

2020 ◽  
Author(s):  
Haruki Kobayashi ◽  
Kazushige Wakuda ◽  
Tateaki Naito ◽  
Nobuaki Mamesaya ◽  
Shota Omori ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Pneumonitis ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Limited Stage ◽  
Lung Abnormalities

Abstract Purpose: Patients with lung cancer and interstitial lung disease treated with radiotherapy have been reported to be at a risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILA) and radiation pneumonitis in patients with limited-stage small cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is unclear for patients with SCLC and ILA treated with chemoradiotherapy. We investigated the impact of ILA on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILA treated chemoradiotherapy. Methods and materials: We retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016. Results: In a univariate analysis, the patients with ILA showed a higher incidence rate of radiation pneumonitis compared with those without ILA (64% vs. 10%); multivariate analysis confirmed that ILA was significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILA showed poorer overall survival than those without ILA (median, 18.9 vs. 67.9 months). Multivariate analysis showed that ILA was a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILA treated with chemoradiotherapy were 36% and 26%, respectively; for those treated with chemotherapy alone were 8% and 0%, respectively.Conclusions: ILA was a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. The prognosis of the patients with LS-SCLC and ILA was poor; however, some patients with ILA treated chemoradiotherapy achieved long-term survival.

scholarly journals Development and Validation of Nomograms for Predicting Survival of Elderly Patients with Stage I Small-Cell Lung Cancer

2020 ◽  
Author(s):  
Yaji Yang ◽  
Shusen Sun ◽  
Feng Xiong ◽  
Yin Xiao ◽  
Jing Huang
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Elderly Patients ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Univariate Analysis ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Predictive Tool

Abstract Background There is a lack of predictive models to determine the prognosis of elderly patients diagnosed with Stage I small-cell lung cancer (SCLC). The purpose of this study was to establish a useful nomogram to predict the cancer-specific survival (CSS) in this patient population.Methods Based on the Surveillance, Epidemiology, and End Results registry database, patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014 were identified. The CSS was evaluated by the Kaplan-Meier method. Patients were randomly split into training and validation sets. In the training cohort, univariate analysis and multivariate analysis by using the Cox regression identified risk factors that affected CSS, and the results were utilized to construct a nomogram for prediction of the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The effectiveness of the nomogram was validated internally and externally by the bootstrap method.Results In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41 months. Multivariate analysis revealed that histologic type, tumor size, age, and AJCC Stage were significant predictors of CSS. A nomogram was constructed according to the results of multivariate COX analysis. The C-indices of the nomogram for training and validation sets were 0.68 and 0.62, indicating that the nomogram demonstrated a favorable level of discrimination. The calibration curves exhibited satisfactory agreement between the actual observation and nomogram prediction.Conclusion A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patients counseling and treatment decision making.

scholarly journals Chemoradiotherapy for limited-stage small-cell lung cancer and interstitial lung abnormalities

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haruki Kobayashi ◽  
Kazushige Wakuda ◽  
Tateaki Naito ◽  
Nobuaki Mamesaya ◽  
Shota Omori ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Pneumonitis ◽  
Univariate Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Limited Stage ◽  
Lung Abnormalities

Abstract Background Patients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy. Methods We retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016. Results In the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P < 0.001). Multivariate analysis confirmed that ILAs were significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILAs showed poorer overall survival than those without ILAs (median, 18.9 vs. 67.9 months, P = 0.0338). Multivariate analysis showed that ILAs were a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILAs treated with chemoradiotherapy were 36% and 26%, respectively, and 8% and 0%, respectively, for those treated with chemotherapy alone. Conclusions ILAs were found to be a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. Patients with LS-SCLC and ILAs who were treated with chemoradiotherapy had both the possibility of long-term survival and risk of radiation pneumonitis.

scholarly journals Digital Pathology and PD-L1 Testing in Non Small Cell Lung Cancer: A Workshop Record

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1800 ◽  
Author(s):  
Fabio Pagni ◽  
Umberto Malapelle ◽  
Claudio Doglioni ◽  
Gabriella Fontanini ◽  
Filippo Fraggetta ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gold Standard ◽  
Digital Pathology ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Standard Quality ◽  
A Minor

A meeting among expert pathologists was held in 2019 in Rome to verify the results of the previous harmonization efforts on the PD-L1 immunohistochemical testing by scoring a representative series of non-small cell lung cancer (NSCLC) digital slides. The current paper shows the results of this digital experimental meeting and the expertise achieved by the community of Italian pathologists. PD-L1 protein expression was determined using tumor proportion score (TPS), i.e., the percentage of viable tumor cells showing partial or complete membrane staining at any intensity. The gold standard was defined as the final PD-L1 score formulated by a panel of seven lung committed pathologists. PD-L1 status was clustered in three categories, namely negative (TPS < 1), low (TPS 1–49%), and high (TPS ≥ 50%). In 23 cases (71.9%) PD-L1 staining was performed using the companion diagnostic 22C3 pharmDx kit on Dako Autostainer, while in nine (28.1%) cases it was performed using the SP263 Ventana kit on BenchMark platform. A complete PD-L1 scoring agreement between the panel of experts and the participants was reached in 57.1% of cases, whereas a minor disagreement in 16.1% of cases was recorded. Italian pathologists performed best in strong positive cases (i.e., tumor proportion score TPS > 50%), whereas only 10.8% of disagreement with the gold standard was observed, and 55.6% regarded a single challenging case. The worst performance was achieved in the negative cases, with 32.0% disagreement. A significant difference resulted from the analysis of the data separated by the different clones used: 22.3% and 38.1% disagreement (p = 0.01) was found in the group of cases analyzed by 22C3 and SP263 antibody clones, respectively. In conclusion, this workshop record proposed the application of a digital pathology platform to share controversial cases in educational meetings as an alternative possibility for improving the interpretation and reporting of specific histological tools. Due to the crucial role of PD-L1 TPS for the selection of patients for immunotherapy, the identification of unconventional approaches as virtual slides to focus experiences and give more detailed practical verifications of the standard quality reached may be a considerable option.

Transient asymptomatic pulmonary opacities and interstitial lung disease in EGFR-mutated non-small cell lung cancer treated with osimertinib

2021 ◽  
pp. 030089162110478
Author(s):  
Gianluca Taronna ◽  
Alessandro Leonetti ◽  
Filippo Gustavo Dall’Olio ◽  
Alessandro Rizzo ◽  
Claudia Parisi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Clinical Variable ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Egfr Mutated

Introduction: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)—clinically benign pulmonary opacities that resolve despite continued osimertinib treatment—and are not associated with the clinical manifestations of typical TKI-associated ILDs. Methods: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients’ clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. Results: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6–80) and median duration time 14 weeks (range 8–37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. Conclusions: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

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