tbuckley/cabot-search huggingface dataset:
PD-1 antibody pembrolizumab administered at non-standard frequency in non-small cell lung cancer (NSCLC).
Authors: Kartik Sehgal, Meghan Shea, Danielle M. McDonald, Mark Huberman, Glen J. Weiss, Paul A VanderLaan, Daniel Botelho Costa, Deepa Rangachari
Journal: Journal of Clinical Oncology (2019)

e20617 Background: Pembrolizumab (P) administered every 3 weeks ± chemotherapy is a standard treatment option for advanced NSCLC. However, there have been no post-approval studies to determine the optimal frequency of administration or if longer intervals between administrations are effective. Methods: We conducted a retrospective review of patients with advanced NSCLC treated with P for at least 4 cycles at a single academic center (02/2016-12/2018). Patients received P-based regimens administered at a standard frequency (3 weeks ± 3 days, group A), ≥ 25% of total treatment cycles outside the standard frequency (group B), and &lt; 25% of total treatment cycles outside the standard frequency (group C). We extracted demographic, tumor characteristic, treatment detail and outcomes data. Results: Of 84 P-treated patients, 43 (51%) were identified as receiving at least 4 cycles (groups A: 17, B: 10, C: 16). There were no significant differences in sex, stage at diagnosis, smoking status, tumor histology, driver oncogene mutations, PD-L1 expression, tumor mutation burden, line of therapy, performance status, or immune-related adverse events (irAEs). Patients in group A were more likely to receive P+chemotherapy (groups A: 41.2%, B: 10%, C: 6.3%; p = 0.03). The reasons for non-standard cycles were: patient-physician preference (65.4% patients), irAEs (15.4%), and non-irAE medical issues (42.3%). Time to treatment discontinuation was significantly longer in groups B &amp; C receiving P-based therapy at longer non-standard intervals and with no statistically significant differences in overall survival. Conclusions: Our data, though limited by sample size and single institution design, shows that a significant proportion of patients receive P at extended intervals in routine clinical practice and with comparable outcomes as would be expected for those with advanced NSCLC receiving P at label-specified 3-week intervals. Given the durability of benefit seen in such patients, this requires confirmation in larger datasets and prospective trials so as to maximize patient experience and clinical outcomes while minimizing financial toxicity.
Observational, multicenter, prospective study to assess the impact on patients' outcome of a systematic screening of oncogenic drivers in advanced cancer: The GETHI XX-16 study.
Authors: Carmen Beato, Paloma Navarro, JF Rodriguez-Moreno, L Miguel Navarro, Beatriz Jimenez Munarriz, Gema Bruixola, Carmen Balana, MD Fenor, Jose Fuster, Francisco Zambrana, Elena Sevillano, Elena Vila-Navarro, Esther NoguerÃ³n, Xabier Mielgo Rubio, Antonio Viudez, Maria Dolores Mediano, Juan Antonio Virizuela, Sergio Ruiz, Elena Mata, Jesus Garcia-Donas
Journal: Journal of Clinical Oncology (2019)

3082 Background: Identification of “agnostic” genetic drivers in cancer is foreseen as a major step forward in precision medicine.Unfortunately, “off label” use of targeted therapies is not widely available and many oncogenic alteration do not present the same behaviour accross all tumor types.We aimed to analyze the real impact on patients management of the implementation of a systematic screening of genetic alterations in centers of the Spanish Group for Rare Cancer (GETHI). Methods: We designed an observational, prospective and multicenter study to molecularly characterize any adult patient with advanced cancer.Formalin fixed paraffin-embedded samples were studied by TrkA-C,ROS1 and ALK immunohistochemistry followed by RT-PCR when positive to confirm gene fusions. Additonally, the Next Generation Sequencing paltform ArcherFusion Plex (able to detect point mutations and rearrangements in 53 cancer related genes) was implemented.Clinical data regarding treatment administered and outcome, were collected from patients identified as harboring drugable alterations. Results: Up to 26 hospitals all over the country got involved in the study. 341 tumoral tissues, representing 41 different histologies were collected. Molecular studies could be performed in 292 samples that led to the identification of 33 patients as harboring somatic oncogenic mutations. 21 were considered druggable and 5 got targeted therapy directed against the alteration identified (three glioblastoma patients with EGFR mutations received erlotinib, one prostate cancer with a BRAF fusion received trametinib and one lung cancer with ALK translocation, previously deemed as negative by standard screening, received crizotinib). One of the glioblastoma patients achieved a long lasting stabilitation and both the prostate and lung tumors presented dramatic partial responses. Conclusions: Though only few cases harboring drugable alteratons got specif treatment, 50% achieved a meanignful benefit. A wide access to molecular screening and targeted drugs could improve the outcome of cancer patients.
Factors affecting differential outcomes in the definitive treatment of anal cancer between HIV+ and HIV- patients.
Authors: Matthew Susko, Stephanie Kim, Ann Lazar, Angela Laffan, Mary Uan-Sian Feng, Alan P. Venook, Chloe Evelyn Atreya, Katherine Van Loon, Mekhail Anwar
Journal: Journal of Clinical Oncology (2019)

3572 Background: Anal cancer is an uncommon malignancy with numerous factors that influence treatment outcomes. Historically, HIV+ patients were restricted from entering clinical trials, limiting data on their outcomes to small retrospective reports. This study seeks to understand the factors related to anal cancer outcomes, specifically the differences between HIV+ and HIV- patients. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Clinical data related to baseline characteristics, treatment parameters, and post-treatment follow-up were extracted for calculation of freedom from local recurrence (FFLR) and overall survival (OS). Univariate analysis (UVA) and multivariate analysis (MVA) were done using cox proportional hazard model, and FFLR and OS were calculated using the Kaplan-Meier method. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. Median age was 56.7 years (IQR: 51.4-63.5), and 47% (N = 52) were HIV+. At median follow-up of 28 months, 12 and 24-month FFLR was 84.1% and 78.2% respectively, with 24-month OS of 87.3%. MVA demonstrated significant association between FFLR and T-stage HR 4.02 (95% CI: 2.14-7.55) p &lt; 0.001, elapsed treatment time (median of 50 days) 1.08 (95% CI: 1.04-1.12) p &lt; 0.001, and diagnosis to treatment start (median time of 15 weeks) 1.05 (95% CI: 1.01-1.08) p = 0.005. Additional analysis with log-rank test for FFLR demonstrated significant difference between patients taking &lt; 50 days to complete treatment (p = 0.03), and &lt; 15 weeks from diagnosis to treatment completion (p = 0.006). In HIV+ patients, post-treatment CD4 &lt; 150 was significantly associated with worse OS on log-rank test (p = 0.016), with pretreatment CD4 values being non-significant. Conclusions: This study represents the largest single institution report of HIV positive patients treated for anal cancer. No difference in local recurrence or overall survival between HIV+ and HIV- patients was elucidated; however, HIV+ patients with lower post-treatment CD4 counts had worse OS. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time.
Disrupting gender norms in health systems: making the case for change
Authors: Katherine Hay, Lotus McDougal, Valerie Percival, Sarah Henry, Jeni Klugman, Haja Wurie, Joanna Raven, Fortunate Shabalala, Rebecca Fielding-Miller, Arnab Dey, Nabamallika Dehingia, Rosemary Morgan, Yamini Atmavilas, Niranjan Saggurti, Jennifer Yore, Elena Blokhina, Rumana Huque, Edwine Barasa, Nandita Bhan, Chandani Kharel, Jay G Silverman, Anita Raj, Gary L Darmstadt, Margaret Eleanor Greene, Sarah Hawkes, Lori Heise, Sarah Henry, Jody Heymann, Jeni Klugman, Ruth Levine, Anita Raj, Geeta Rao Gupta
Journal: The Lancet (2019)
Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC: A validation study in Chinese patients.
Authors: Chen Chen, Xiaojie Huang, Mingzhe Song, Wei Yin, Alicia Hulbert, Malcolm Brock, James Herman, Fenglei Yu, Wenliang Liu
Journal: Journal of Clinical Oncology (2019)

8522 Background: Our previous study revealed that high diagnostic accuracy for early stage lung cancer could be obtained in plasma samples with ultrasensitive DNA hypermethylation detection methods called MOB-qMSP. In this study, we sought to validate and also improve the diagnostic accuracy of lung cancer screening with modified MOB-qMSP approach in Chinese patients. We also develop a lung cancer specific gene panel for Chinese patients. Methods: We included patients with small lung nodules (less than 3cm in diameter) on CT scan screening and conducted a case-control study. Cases (n=138) had pathological confirmation of Non-Small Cell Lung Cancer (NSCLC) lesions staged IA or IB. Controls (n=65) had pathological confirmation of non-cancerous lesions. Plasma samples were obtained pre-operatively. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5 and PAX5B) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP. Results: DNA methylation was detected in plasma more frequently in cases compared to controls (p&lt;0.001) for 5 out of 8 genes. The sensitivity and specificity for lung cancer diagnosis using the best individual gene was 64-85% and 55-79% respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 92% and 78%. Area under the Receiver Operating Curve (AUC) for this panel was 0.90, 95% CI (0.86-0.96). Cross validation combining gene methylation with clinical information correctly predicted lung cancer in 86% of subjects using plasma detection. Furthermore, we analyzed the sensitivity and specificity of the same three-gene combination in cases subgroups regarding the tumor size and the results are as follow: in subgroup with tumor size of 2-3cm, the sensitivity and specificity were 94% and 87%, and the AUC was 0.96, 95% CI (0.91-0.99); in subgroup with tumor size of 1-2 cm, the sensitivity and specificity were 92% and 80%, and the AUC was 0.90, 95% CI (0.84-0.96); in subgroup with tumor size less than 1cm, the sensitivity and specificity decreased to 66% and 87%, and the AUC was 0.77, 95% CI (0.64-0.88). Conclusions: This study validates our previous study but in Chinese patients that it is possible to obtain high diagnostic accuracy for early stage NSCLC using a panel of methylated promoter genes in plasma samples with ultrasensitive MOB-qMSP, especially in patients with tumor of larger size. These epigenetic biomarkers could potentially be used to identify patients with high risk of lung cancer development.
Anomalous Origin of the Right Coronary Artery From Contralateral Side: A Series of 17 Cases
Authors: Sedat Köroğlu, Arif Suner, Cemal Tuncer, Ahmet Akcay, Alper Nacar, Burak Altun, Talantbek Batyraliev, Mustafa Gokce, Beyhan Eryonucu, Remzi Yılmaz
Journal: Journal of the American College of Cardiology (2013)
Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).
Authors: Sara M. Tolaney, Romualdo Barroso-Sousa, Tanya Keenan, Lorenzo Trippa, Jiani Hu, Ines Maria Vaz Duarte Luis, Gerburg M. Wulf, Laura Spring, Natalie Faye Sinclair, Chelsea Andrews, Jessica Demeo Pittenger, Edward T. Richardson, Deborah Dillon, Nancy U. Lin, Beth Overmoyer, Ann H. Partridge, Eliezer VanAllen, Elizabeth A. Mittendorf, Eric P. Winer, Ian E. Krop
Journal: Journal of Clinical Oncology (2019)

1004 Background: Studies of checkpoint inhibitor monotherapy show only modest activity in HR+ MBC. We report data from the first randomized study comparing E plus P versus E alone in HR+/HER2- MBC. Methods: Eligible patients (pts) had HR+/HER2- MBC, ≥2 lines of hormonal therapies and 0-2 lines of chemotherapy for MBC. Pts were randomized 1:1 to E 1.4mg/m2 intravenously (IV) on d1 and d8 with P 200 mg/m2 IV on d1 of a 21-day cycle (Arm A) or E alone (Arm B). At time of progression, pts in arm B could crossover and receive P alone. Primary endpoint was progression-free survival (PFS). Key secondary endpoints were: objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), neutrophil-lymphocyte ratio (NLR), tumor mutation burden (TMB), and genomic alterations by next generation sequencing on archival tissue. Results: 88 pts initiated protocol therapy; the median age was 58, median prior lines of chemotherapy 1, prior lines of hormonal therapy 2. Median follow-up was 6.3 months. Median PFS and ORR were not different between Arms A and B (PFS 4.1 vs 4.2 months p = 0.38; ORR 25% and 34% respectively (p = 0.49). 14 patients initiated crossover treatment with pembrolizumab; 1 patient experienced a PR (ORR 7%). All-cause AEs occurred in 100% of pts (G3-4, 54.6%) including 2 treatment related deaths on Arm A, both from known AEs attributed to both drugs. PD-L1 assay was performed in 65 pts: 24 (36.9%) had PD-L1 positive ( &gt; 1% with 22C3, centrally tested) tumors. PD-L1 status, TILs, NLR, TMB, and genomic alterations were not associated with PFS (Table). Updated data, including OS and genomic results, will be presented. Conclusions: Among pts with HR+/HER2- MBC, the combination of E and P was not associated with longer PFS than E alone in the ITT or PD-L1+ population, though the PD-L1+ subgroup had very limited power to assess P benefit. Clinical trial information: NCT03051659. [Table: see text]
Real-world data analysis of ovarian cancer (OC) maintenance utilization among maintenance eligible patients.
Authors: David Garofalo, Ebru Aydin, Monica Labrador, Jennifer Webster, Greg Brown, Joseph Donaldson, Hinco Jasper Gierman, Prateesh Varughese, Ash Malik, Jeffrey A. Scott
Journal: Journal of Clinical Oncology (2019)

5579 Background: Approximately 1% of US women will be diagnosed with epithelial OC during their lifetime. OC patients who achieve a response to platinum-based chemotherapy may benefit from maintenance therapy, with the goal of inducing a lasting remission or extending the time interval before progression without any deleterious impact on quality of life 1 . This analysis, based on real world data sourced from US community oncology practices, was designed to assess the current utilization of maintenance therapy among maintenance eligible patients. Methods: This analysis utilized the Integra Data Exchange (DTX) database, a deidentified data source from community oncology practice systems (EMR, practice management, paid claims). This retrospective study included 3,629 OC patients with at least two visits between 7/16/16 and 4/16/18. 398 patients who completed 2nd line or later platinum-based chemotherapy for 4-9 cycles and/or had a complete/partial response between 1/1/17 and 7/31/18 were included. Potential maintenance therapy options were monotherapy of PARP inhibitors, bevacizumab, and non-platinum-chemotherapy agents. Rate of maintenance therapy after platinum-based treatment was assessed. Results: Our real-world analysis found that 49% of 398 maintenance eligible patients received maintenance therapy at least once following response to 2 nd line or later platinum chemotherapy. Among those that received maintenance, 46% received PARPi, 28% bevacizumab, and 26% non-platinum chemotherapy. Further, 56% of women with BRCA mutations received maintenance treatment, compared with 49% of women without BRCA mutations. Conclusions: Though there are several options available, 51% of OC women studied who could potentially benefit from maintenance treatment did not receive maintenance. Only 56% of BRCA mutation carriers were targeted for maintenance in the real world. Among patients that receive maintenance therapy following 2 nd line or later platinum chemotherapy 46% received a PARPi based regimen. 1) Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomized controlled trial. Lancet Oncol. 2018 Aug;19(8).
Half-dose olaparib reduction: Safe and efficient dose in multi-treated Mexican ovarian cancer patients.
Authors: Dolores Gallardo-Rincon, Gabriela Alamilla, Edgar Montes-Servín, David Michel-Tello, Elizabeth Montes-Servín, Alfredo Toledo-Leyva, Antonio Bahena-Gonzalez, Ernesto Gonzalez-Ibarra, Flavia Morales-Vasquez, Claudia Cano Blanco, Raquel Espinosa-Romero
Journal: Journal of Clinical Oncology (2019)

e17101 Background: Ovarian cancer (OC) is the most common gynecological cancer worldwide, and in Mexico stands as the 2nd gynecological cancer-related death cause with 4,759 new cases yearly. PARP inhibitors in BRCA1/2 mutated patients offer disease control after response to chemotherapy with few side effects and minimal impact on quality of life. The primary objective of this study was to evaluate the clinical benefit of Olaparib half-dose reduction in multi-treated Mexican OC patients. Methods: Nineteen OC BRCA1/2 positive patients were enrolled (Nov 2016-Dec 2018), at the Instituto Nacional de Cancerología, Mexico. Eligible patients had received &gt; 2 previous platinum-based lines. Olaparib dose was 800 mg/day, as maintenance therapy after complete or partial response. Half-dose administration was allowed in grade 3 toxicity events. Median PFS curves were estimated by the Kaplan–Meier method. Results: The most common mutation in OC patients was BRCA1 (78.9%), four patients had founder mutation (Del9-12). Eleven patients (57.9%) received Olaparib in ≥4 lines. Nine patients required dose adjustment following hematological (42.1%) and gastrointestinal toxicity (5.2%). There was not statistical differences between complete-dose and half-dose administration groups. However patients with founder BRCA1 mutation did not require dose adjustment ( P= 0.033) and multi-treated (≥4 lines) patients were more susceptible to develop hematological toxicity ( P= 0.030). The median PFS was 12.02 months, patients HGSP histology had a better PFS compared with endometroid histology (14.8 Vs 5.19; P= 0.020). BRCA1 founder mutated patients had a better PFS compared with other BRCA mutations (NR Vs 11.30; P= 0.050). The median PFS in first, second and third or more recurrence was NR Vs 14.8 Vs 8.3; P= 0.050. We did not find statistical difference in the PFS in half-dose reduction compared with complete-dose groups (9.6 Vs NR; P= 0.221). Conclusions: We provide evidence that using Olaparib in first and second recurrence had better outcome compared with third or more recurrence. However the recommended dose exhibits a high toxicity profile; therefore half-dose reduction in multi-treated patients needs to be suggested in Olaparib OC guidelines as a safety and effective strategy.
Outcomes of post-operative treatment with concurrent systemic therapy and radiotherapy (RT) in intermediate (INT) risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.
Authors: Jessica Lyn Geiger, Neil McIver Woody, C. Jillian Tsai, Ahmed I. Ghanem, Neal Dunlap, Howard Liu, Brian B. Burkey, Eric Lamarre, Jamie Ku, Joseph Scharpf, Nikhil Purushottam Joshi, Jimmy J. Caudell, Farzan Siddiqui, Sandro Porceddu, Nancy Y. Lee, Shlomo A. Koyfman, David J. Adelstein
Journal: Journal of Clinical Oncology (2019)

e17567 Background: Patients (pts) with adverse pathologic factors in resected OCSCC excluding positive surgical margins or extranodal extension represent a group of INT risk disease. Though not standard of care, adjuvant CRT is often used in INT pts. We conducted a multi-institutional study to evaluate factors associated with improved outcomes in INT pts treated with or without chemotherapy. Methods: An IRB-approved collaborative database of patients with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by pathologic features and adjuvant therapy. Kaplan Meier curves, log-rank p-values and multivariate analysis (MVA) were used to describe outcomes by treatment including locoregional control (LRC) and disease free survival (DFS). Results: From a total sample size of 1270 patients, 455 INT risk pts were treated with primary surgical resection and adjuvant therapy; 95 received CRT, 274 received RT alone, and 86 received RT without recorded chemotherapy. 49% of pts had perineural invasion (PNI), 24.8% lymphovascular space invasion, 21.5% poorly differentiated histology, 47.3% with pT3/4 disease, and 27.9% with &gt; 2 lymph node positive (LN+). 55.8% of CRT pts were treated with cisplatin. &gt; 2 LN+ was the only significant predictor of LRC (HR 1.49, p= 0.049). PNI and &gt; 2 LN+ were significant predictors of DFS (HR 1.52, p= 0.003 and HR 1.76, p&lt; 0.001). On MVA, after adjusting for &gt; 2 LN+, treatment with cisplatin-RT was borderline significant for LRC (HR 0.52, p= 0.08). 3 year LRC in pts with &gt; 2 LN+ was 84.4% in pts treated with cisplatin-RT compared with 64.9% for RT alone. Conclusions: The addition of cisplatin-based CRT to INT risk pts is controversial but among pts with &gt; 2 LN+ there was a trend toward benefit. This study is limited by small numbers of pts treated with CRT, though these results highlight the need for further investigation in this population to identify INT pts who would benefit from adjuvant therapy intensification.
Predicting future cancer incidence by age and gender.
Authors: Wesley B. Garner, Benjamin D. Smith, Jacob Ezra Shabason, Grant Richard Williams, Michelle Y. Martin, Matthew T. Ballo, Noam Avraham VanderWalde
Journal: Journal of Clinical Oncology (2019)

1559 Background: Cancer remains a substantial and unique burden on society. While the impact of changing demographics on cancer incidence has previously been characterized (Smith et al, JCO, 2009), this has not been done with updated population data. Our objective was to update projections on the number of new cancer diagnoses in the United States by age and gender through 2040. Methods: Population-based cancer incidence data were obtained using SEER 18 delay-adjusted data. Population estimates were made by age, race, and gender using the 2010 US Census data population projections to calculate future cancer incidence rates. Trends in age- adjusted incidence rates for 23 cancer types were calculated as previously described (Edwards et al, Cancer, 2014). Results: From 2020 to 2040 the projected total cancer incidence will increase by almost 30% from 1.86 million to 2.4 million. This increase is due to the projected increase in population growth, particularly in older individuals. The population of older adults will represent a growing proportion of total cancer diagnoses. Specifically, patients ≥65 years old will make up 69% of all new cancer diagnoses, while 13% of new diagnoses will be in patients ≥85 years old by 2040 (see Table). Cancer diagnoses in females are projected to rise 27%, while male cancer diagnoses are projected to increase by 32% from 2020 to 2040. The incidence rates for lung, colorectal, and prostate cancer are expected to decline, while those for thyroid, liver, melanoma and myeloma are expected to increase. Conclusions: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial and will continue to disproportionately affect older adults. The growing proportion of older cancer patients and changes in site-specific cancer incidence rates remain of particular interest. These projections should help guide future health policy and research priorities. [Table: see text]