bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence patterns following curative therapy for stage I NSCLC.
Authors: Butts Emily , Gococo-Benore Denise , Pai Tanmayi , Chen Ruqin , Manochakian Rami , Lou Yanyan 
Published: May 2020

e21069 Background: Lobectomy remains the standard of care for definitive management of stage I non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is considered primarily for patients who were either unwilling to have surgery or deemed to be medically unfit for surgery. Current NCCN guidelines indicate the use of CT for surveillance following curative-intent therapies and recommend CT every 6 months for 2-3 years followed by CT annually without clear guidance on how long to keep doing annual CT scans. This study aims to evaluate the patterns of lung cancer recurrence within and beyond five years post curative therapy. Methods: Patients diagnosed with stage I NSCLC and treated with either curative surgery or SBRT from 1998-2016 at Mayo Clinic Florida were identified. Through retrospective chart review, data was collected on clinical and demographic features, surveillance imaging, pathology, time to recurrence or new primary lung cancer, and location of recurrence (loco-regional vs. distant). Statistical analysis with chi-square test was performed to identify risk factors associated with recurrence. Results: In total, 203 patients with stage I NSCLC were identified with most patients treated with surgery (n = 181) compared with SBRT (n = 22). Median time of follow up is 85 months. Overall, 48 patients (23.6%) developed a recurrence, with the median time to recurrence of 22.3 (3.9-69.8) months. Most recurrences were identified within 5 years from curative therapy (42/48) with 6 patients having a recurrence between 5 and 10 years post curative therapy. Of the 37 patients followed for more than 10 years, there were no recurrences. Twenty seven patients had new primary lung cancers identified and among them, 15 were found within 5 years, 10 found between 5-10 years and 2 found beyond 10 years. Median time to new primary lung cancer was 58.1 months. A positive smoking history and stage IB were found significantly associated with lung cancer recurrence (chi-square test P = 0.007 and P = 0.04 respectively), while age, gender, histology, grade, and treatment type had no association. Conclusions: In this study of 203 patients with stage I NSCLC treated with curative intention, there was no evidence of recurrent disease after 10 years following curative therapy, questioning the utility of continued annual CT surveillance once patients hit this milestone.
Impact of clinical and pathological variables on stage I non-small cell lung cancer outcomes.
Authors: Lee Matthew C , Stefanov Dimitre C , Angert Mallorie B , Cohn Erica C , Kohn Nina , Esposito Michael J , Seetharamu Nagashree 
Published: May 2020

e21071 Background: Stage I patients (pts) have 5-year survival ranging 50-75% suggesting heterogeneity within. While American Joint Committee on Cancer 8th edition upstages tumors with visceral pleural invasion (VPI) to IB, other histological features namely lymphovascular invasion (LVI), micropapillary pattern (MIP), spread through airspace (STAS) & neuroendocrine differentiation (NE) may also affect prognosis. This retrospective single institution study evaluated influence of these factors along with pt variables age, gender, smoking, Charleston comorbidity index (CCI) & chemotherapy (CT) on recurrence & mortality. Methods: 351 resected stage I cases from 2015-2019 were included. Data was summarized as means (standard deviation/SD) or percentages. Association between variables & outcomes (measured from diagnosis till event or last visit if no event) were investigated using Univariate & Multiple Cox proportional hazards models. Survival curves were compared using the Log-Rank test when the assumption for the proportional hazards was not satisfied. All predictors were included in the multiple Cox regression models based on their clinical importance. P < 0.05 was considered statistically significant. SAS 9.4 (SAS Institute, Cary, NC) was used for the analysis. Results: Mean age was 69.62 years (9.83). Majority were female (57.3%), smokers (76.9%), & had adenocarcinoma (AC) (78.6%). 39% had COPD & mean CCI was 6.3 (1.74). 193 (55%) pts had lobectomy or larger procedure while 158 (45%) had sub-lobar resection. 45 (12.8%) pts received CT. Recurrence & death occurred in 33 (9.4%) & 15 (4.3%) pts respectively. Univariate models indicated higher recurrence risk with NE (HR = 4.18 95% CI 1.47-11.9, p = 0.0075), LVI (HR = 2.68, 95% CI 1.03-6.94, p = 0.0423), COPD (HR = 3.28 95% CI 1.56-6.9, p = 0.0017), age (HR = 1.05 95% CI 1.01-1.09, p = 0.0212), & CCI (HR = 1.57 95% CI 1.35-1.83, p < .0001). CT was also associated with increased recurrence risk (HR = 8.61, 95% CI 4.28-17.33, p < .0001). Multivariable model for recurrence retained significance for CT & CCI. Age (HR = 1.07 95% CI 1.01-1.14, p = 0.0312), CCI (HR = 1.27 95 % CI 1.02-1.59, p = 0.0347) were associated with mortality in univariate models. Multivariate analysis for mortality wasn’t feasible due to few events. Conclusions: Histological features other than VPI may be associated with recurrence. Pts who received CT had increased recurrence but they possibly had multiple risk factors or other adverse features not assessed here. Limitations included retrospective nature, limited sample size & small number of events.
Phase II trial of biweekly carboplatin and nab-paclitaxel with concurrent radiotherapy for patients with locally advanced unresectable stage III non-small cell lung cancer.
Authors: Tanaka Hisashi , Okumura Fumihiko , Tabe Chiori , Ishioka Yoshiko , Itoga Masamichi , Taima Kageaki , Hasegawa Yukihiro , Yokouchi Junichi , Takanashi Shingo , Aoki Masahiko , Tasaka Sadatomo 
Published: May 2020

e21078 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small cell lung cell cancer (LA-NSCLC). We previously reported the phase I study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with RT. Recommended dose for phase II study was carboplatin (AUC 4) and nab-PTX (100 mg/m2) (J Clin Oncol 2015 suppl; abstr 7529). Here we report the phase II part designed to assess the efficacy of biweekly carboplatin and nab-PTX with concurrent RT (UMIN000023802). Methods: Patients with inoperable stage Ⅲ NSCLC were treated with carboplatin (AUC 4) and nab-PTX 100 mg/m2 on days 1, 15, and 29. Thoracic radiotherapy was administered from day 1 to a total dose of 60 Gy in 30 fractions. Consolidation chemotherapy after CCRT was 2 cycles of carboplatin (AUC 6) on day 1 and nab-PTX 100 mg/m2 on days 1, 8, and 15. The primary endpoint for the phase II part is 2-year overall survival (OS) rate. Assuming an expected survival rate was 60% and a lower limit was 35% (alfa 0.05, beta 0.2). Secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), OS, and safety profile. Results: A total of 28 patients (median age 66 years, male 94%) were enrolled. Of the evaluable patients (n = 28), the rate of 2-year OS was 67.8% (95% CI: 49.3–82.1). The ORR was 96%, a median follow-up time was 33.2 months. Median PFS was 18.2 months (95% CI 13.1–not reached), and median OS was not reached (95% CI, 25.6–not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.6%) and pneumonitis (3.6%). Conclusions: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT therapy was well tolerated and promising systemic antitumor activity for patients with LA-NSCLC. Clinical trial information: 000023802 .
Clinical characteristics and outcomes of simultaneous multiple primary lung cancer.
Authors: Liu Ying 
Published: May 2020

e21088 Background: Simultaneous multiple primary lung cancer (sMPLC) is detected increasingly nowadays with the development of image technology. But it has not been well characterized. Methods: All consecutive patients diagnosed as sMPLC according to Martini-Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 were enrolled in our center. The clinical characteristics and outcomes were compared between patients with same histology and different histology. Results: A total of 336 patients were enrolled, consist of 297 (88.4%) patients with same histology and 39(11.6%) patients with different histology. Compared to patients with same histology, patients with different histology were more common male (87.2% vs. 34%, p < 0.001) and diagnosed at an older age (54 [62-69] vs. 59 [52-65], p < 0.001). Also, more than half of them (56.4%) had respiratory symptom or pain before diagnosis and most of them had smoking history (79.5% vs. 19.2%, p < 0.001). During follow-up, 5 patients were lost and 16 patients were died, contributing the 1-, 2-, and 3-year survival of overall patients was 97.7%, 96.1%, and 92.2%, respectively. Importantly, the survival rate was lower in patients with different histology (1-, 2-, and 3-year 88.5%, 75.4, and 64.3%) than same histology (1-, 2-, and 3-year 99.2%, 99.2, and 96.8%) (p < 0.001). Conclusions: Although relative less common in sMPLC, patients with different histology showed different clinical features and worse prognosis. [Table: see text]
Comprehensive investigation of mutational features of various lung adenocarcinoma histological subtypes among Chinese patients.
Authors: Han Yuchen , Xiang Chan , Teng Haohua , Zhu Lei , Shao Jinchen , Zhao Jikai , Ma Shengji , Lin Jing , Zheng Jingjing , Lizaso Analyn 
Published: May 2020

e21090 Background: Lung adenocarcinoma (LUAD) is further classified into several histological subtypes according to the World Health Organization classification; however, data on the molecular profile of these histological subtypes are limited. In this study, we aimed to investigate the mutational features of various LUAD histological subtypes among Chinese patients. Methods: We retrospectively analyzed clinical, histopathologic, and sequencing data from 3,425 consecutive patients diagnosed with stage IA-IVB LUAD between January 2017 to December 2019 at the Department of Pathology. Results: Based on histologic subtype, the cohort comprised of 0.2% atypical adenomatous hyperplasia (AAH, n = 6), 7.2% adenocarcinoma in situ (AIS, n = 246), 14.0% minimally invasive adenocarcinoma (MIA, n = 479), and 78.6% invasive adenocarcinoma (INV, n = 2,694), including 42.0% acinar (n = 1,438), 12.7% papillary (n = 435), 8.8% lepidic (n = 302), 8.5% solid (n = 290), 3.2% micropapillary (n = 109), 2.8% invasive mucinous (n = 95), 0.6% enteric (n = 21), 0.1% fetal (n = 3), and 0.1% colloid (n = 1). Analysis of mutation profiles revealed significantly higher mutation detection rates of ERBB2 ( P< 0.01), BRAF ( P< 0.01), and MAP2K1 ( P= < 0.01) among patients with AIS, AAH and MIA as compared to patients with INV. Meanwhile, TP53 ( P< 0.01) and EGFR ( P< 0.01) mutations were significantly higher among patients with INV as compared to patients with AIS and MIA. Among the invasive subtypes, patients with invasive mucinous adenocarcinoma had significantly higher KRAS mutation rate (75%, P< 0.01). Lepidic (81%), acinar (80%), papillary (77%), and micropapillary (66%) were the subtypes with the highest EGFR mutation rates. Conclusions: By analyzing the genomic data of a large cohort of patients, our study provides a more comprehensive outlook of gene mutations according to LUAD histological subtypes. Enrichement of actionable mutation in particular histological subtype contributes to more treatment option and better clinical outcomes as compared to other histological subtype, indicating the clinical relevance of performing comprehensive mutation profiling in addition to histopathologic analysis in all LUAD patients.
Real-world outcomes of pembrolizumab in peritoneal mesothelioma.
Authors: Marmarelis Melina Elpi , Wang Xiao , Roshkovan Leonid , Walker Suzanne , McNulty Sally , Ciunci Christine Agnes , Muira John , Katz Sharyn I. , Cengel Keith A. , Karakousis Giorgos , Langer Corey J. 
Published: May 2020

e21094 Background: Clinical trials evaluating pembrolizumab (P) in malignant mesothelioma (MM) have included small numbers of peritoneal MM (MPM) patients (pts), but the efficacy of P in the MPM subpopulation remains unclear. We evaluated the efficacy of P in a cohort of MPM pts treated at our institution. Methods: This retrospective cohort study identified MPM pts via ICD9/10 codes seen at our institution between 1/1/2009 and 9/1/2019. Pts were included if they received P as treatment for MPM. Median progression free survival (PFS) and median overall survival (mOS) were estimated from Kaplan-Meier curves. PFS was defined as the start of P until radiologic or clinical progression. Best overall response rate (BOR) and disease control rate (DCR) were determined retrospectively using RECIST 1.1 criteria. Results: We identified 13 non-papillary MPM pts who received P. All pts had received prior chemotherapy (12 platinum/pemetrexed, 1 pemetrexed). Median age at diagnosis was 65.6 years; 77% were white; 46% never smokers; 62% with known asbestos exposure; 70% epithelioid/15% biphasic/ 7.7% sarcomatoid/ 7.7% desmoplastic. BOR to P was 18% (Partial response (PR): 2, Progressive disease (PD): 2, Stable disease (SD): 7, Lost to follow up: 2). DCR was 81% and mPFS 5.7mo. From the start of P mOS was 20.9 mo. Only 3 pts had known PDL1 positivity (1%, 2%, 80%), 4 were negative, 6 untested. Median PFS was not statistically different between PDL1 positive and negative pts (mPFS 5.1mo vs. 5.7 mo, log rank p = 0.73, respectively). Three pts experienced a PFS of > 2 years (PDL1/BOR/% tumor change: Unknown/SD/19%, Negative/SD/-21%, 80%/PR/-70%). The patient with PDL1 80%, biphasic histology and a PR experienced skin toxicity requiring a treatment break. Outcomes for epithelioid histology vs non-epithelioid after P did not differ statistically (mPFS 5 mo vs 39 mo, log rank p = 0.14; mOS 17.5 mo vs NA, log rank p = 0.31). Conclusions: In a real world setting, P has clinically meaningful activity in a PDL1 unselected cohort of MPM pts and should be considered a treatment option for this subpopulation of MM. We did not detect a difference in outcomes based on PDL1 level or histology.
Phase II study of amrubicin for previously treated patients with malignant pleural mesothelioma.
Authors: Akagi Kazumasa , Ikeda Takaya , Nakatomi Katsumi , Taniguchi Hirokazu , Shimada Midori , Gyotoku Hiroshi , Dotsu Yosuke , Umeyama Yasuhiro , Tomono Hiromi , Kitazaki Takeshi , Fukuda Masaaki , Soda Hiroshi , Senju Hiroaki , Takemoto Shinnosuke , Yamaguchi Hiroyuki , Fukuda Minoru , Mukae Hiroshi 
Published: May 2020

e21095 Background: Malignant pleural mesothelioma (MPM) is a rare disease with few effective treatments and poor prognosis. Although pemetrexed (PEM) and cisplatin for the first-line treatment, and nivolumab for the second-line are considered as the standard treatment for patients with unresectable disease, these effects are still limited. There are no other effective agents for second-line treatment, although PEM-based regimens, vinorelbine, gemcitabine are recommended by some guidelines. Novel therapeutic strategies for the treatment of MPM are urgently required. Amrubicin (AMR) is a chemically synthesized anthracycline-based anticancer drug that inhibits cell growth by stabilizing the cleavable complex via topoisomerase II. The same anthracycline; adriamycin was one of the key drugs for MPM prior to the appearance of PEM, but its efficacy against MPM has not been revealed. Thus, we planned a phase II study of AMR therapy for previously treated MPM. Methods: Eligibility criteria were previously treated patients with unresectable MPM, performance status 0-2, age≦75, and adequate hematological, hepatic and renal function. Patients were treated with injections of AMR 35 mg/m2 on days 1, 2, and 3. The treatments were repeated every 3-4 weeks. The primary endpoint was the response rate (RR), the secondary endpoints were safety, progression-free survival time (PFS), overall survival time (OS). Results: Although the number of target cases was 32 cases, case registration was delayed and evaluation was performed with 10 cases enrolled. Patients' characteristics were as follows: male/female = 9/1; performance status 0/1/2 = 0/10/0; median age (range) = 67 (49-73); histology epithelial/sarcomatoid/mixed = 4/3/3; stage (IMIG) I/II/III/IV/postoperative recurrence = 0/1/4/4/1. RR was 10.0% (1/10), median PFS was 1.6 months and median OS was 6.6 months. Disease control rate was 50.0% (5/10). Adverse events of Grade 3 or 4 were neutropenia 60.0% (6/10), thrombocytopenia 10.0% (1/10), anemia 10.0% (1/10), febrile neutropenia 10.0% (1/10), and pneumonia 10.0% (1/10). Conclusions: This study demonstrated that AMR therapy for previously treated MPM was tolerable. The efficacy was limited, but may be effective in some cases. Clinical trial information: UMIN000006381 .
Extensive small cell lung cancer (SCLC) chemotherapy: A population kinetics assessment.
Authors: Stewart David J. , Brule Stephanie Yasmin 
Published: May 2020

e21101 Background: Most progression-free (PFS) and overall survival (OS) curves fit exponential decay models on nonlinear regression analysis (NLRA). Log-linear curve shape varies with tumor & therapy type: straight line vs inflection to right (2 phase decay due to 2 distinct subpopulations with differing sensitivities) vs convex (downward inflection, eg due to stopping therapy that is slowing tumor growth).1 We compared SCLC to other cancers. Methods: As previously described,1 we did NLRA of published PFS & OS curves for etoposide-platinum in SCLC. We also assessed various therapies in other cancers. We calculated PFS & OS half-lives and classified curves by log-linear shape. Results: Of 18 evaluable SCLC PFS curves, 14 (78%) were highly convex & 18 (100%) were moderately or highly convex, compared to 35/888 (4%) highly convex & 186 (21%) moderately or high convex curves for other cancers (p < 0.0001). Of 24 evaluable SCLC OS curves, 12 (50%) were highly convex & 24 (100%) were moderately or highly convex, compared to 15/363 (4%) being highly convex & 87 (24%) moderately or highly convex for other cancers (p < 0.0001). In SCLC, 6 vs 4 cycles induction therapy minimally changed PFS half-life (median across studies 5.5 vs 5.2 months, p = 0.27) or OS half-life (9.5 vs 10.4 months, p = 0.06). PFS half-life correlated with OS half-life for other cancers (n 320, Spearman r 0.81, p < 0.0001) but not for SCLC (n 18, r 0.04, p = 0.86). Post progression survival (PPS) correlated positively with PFS half-life for other cancers (n 376, r 0.68, p < 0.0001) but correlated negatively for SCLC (n 18, r -0.43, p = 0.07). SCLC PFS curves had an initial downward inflection at a median of 2.9 months (where 87% of patients are still progression-free), followed by a 2nd inflection point at 4.5 months (where 71% are still progression-free). Median PFS half-life was 14.6 months prior to the 1st inflection point vs 1.9 months after the 2nd inflection point. Our analysis methods1 suggest that after the 2nd PFS inflection point, 23% of patients would progress by the next scan if scans are done every 3 weeks, while 40% would progress by the next scan if they are done every 6 weeks. Conclusions: PFS & OS curves for SCLC are more often highly convex than for other cancers since SCLC is sensitive to chemotherapy but progresses rapidly after induction therapy is completed. Giving 6 rather than 4 induction cycles makes no OS difference. New maintenance strategies are needed. Very short PFS half-lives post induction suggest that frequent follow up scans should be done for patients who are candidates for 2nd line therapy. 1. Stewart. Cancer Med 2019; 8:6871
Genomic characterization of circulating tumor DNA from Chinese advanced small-cell lung cancer to reveal potential therapeutic opportunities.
Authors: Yang Jing , Lu Jingli , Zhang Qiwen , Fu Xiaomin , Chen Hui , Zhao Xiaochen , Bai Yuezong , Zhang Xiaojian 
Published: May 2020

e21111 Background: Molecular profiling via next-generation sequencing (NGS) has been applied to select patients benefiting from targeted therapy or immunotherapy. Sequencing of blood-derived circulating tumor DNA (ctDNA) presents an alternative for advanced cancers given the challenge of obtaining tumor biopsies. We identified potentially actionable genomic alterations (GAs) in Chinese advanced small-cell lung cancer (SCLC) patients using ctDNA testing. Methods: Blood samples from 119 patients with advanced SCLC were sequenced via target deep sequencing covering 150 or 189 cancer-related genes and 100 microsatellite loci. Blood tumor mutation burden (bTMB), defined as the number of somatic single-nucleotide variants, short insertions and deletions (SNV/Indels) in examined coding region, was calculated in 93 patients. High bTMB was set to 10 that ranks top 25% in all SCLC patients. Results: The total number of GAs was 1156 in 127 genes, with an average of 9.7 GAs per sample ranging from 1 to 31. All patients harbored at least one GA and 107/119 patients had at least one GA with clinical significance. TP53 (82.4%) was the commonly altered gene followed by RB1 (57.1%), LRP1B (41.2%), FAT1 (25.2%), FAM135B (23.5%), PIK3CA (21%). GAs were detected frequently in cell cycle pathway (83.2%), PI3K/AKT/mTOR pathway (33.6%), RTK-RAS-MAPK pathway (29.4%), and DDR pathway (10.1%). Overall, 54 (45.4%) patients had alterations with therapeutic relevance, including 2 high blood microsatellite instability and 23 high bTMB that might benefit from immune checkpoint inhibitors. Actionable SNV/Indels were identified, including EGFR mutation (3), KRAS/HRAS mutation (5), DNA damage repair (DDR) pathway (4; including ATM, BRCA1, BRCA2), and PI3K/AKT/mTOR pathway (10; including PIK3CA, PTEN) that might benefit from EGFR tyrosine kinase inhibitors, RAS inhibitors, PARP inhibitors and mTOR inhibitors, respectively. We also found amplification of HER2 (3), FGFR1 (14), and MET (3) that might benefit from anti-HER2 antibodies, FGFR1 inhibitors and MET inhibitors, respectively. Conclusions: To our knowledge, this is the first large-scale analysis of blood-derived ctDNA in Chinese advanced SCLC. Potentially actionable GAs were detected in 45.4% patients. Deep sequencing of ctDNA could provide molecular profiles and might optimize treatment decision in advanced SCLC.