tbuckley/cabot-search huggingface dataset:
Prognostic impact of first treatment choice in EGFR mutant non-small cell lung cancer (mNSCLC) patients (pts) per mutation type; retrospective analysis.
Authors: Jair Bar, Maya Gottfried, Julia Dudnik, Dov Flex, Shoshana P. Keren-Rosenberg, Abed Agbarya, Amir Onn, Mor Tal Moskovitz, Natalie Maimon, Irena Lazarev, Nir Peled, Noa Popovits-Hadari, Haim Biran, Damien Urban, Liv Herscovici, Mira Wollner
Journal: Journal of Clinical Oncology (2015)

e19120 Background: mNSCLC pts benefit from EGFR tyrosine kinase inhibitors (TKIs) but also from chemotherapy; the optimal sequencing of these treatments in not known. Methods: mNSCLC pts that received systemic treatment for stage 4 disease were eligible. De-identified data was retrieved from medical records of 6 cancer departments. Overall survival (OS) from diagnosis of metastatic disease was the primary outcome. Multivariate analyses included first line of treatment for metastatic disease (chemotherapy vs. TKI), EGFR mutation type, age, sex, stage at diagnosis, histologic subtype, smoking and performance status (PS). Based on our pilot study, to demonstrate OS HR ≥ 2.0 between pts treated with chemotherapy vs. TKI as first treatment, with significance level of 5% and power of 90%, we needed at least 88 events. Results: 287 pts were eligible, median age 66 years, 38% male, 76% stage 4 at diagnosis, 89% adenocarcinoma, 37% ever smokers, 79% PS 0-1. TKI was first treatment in 83%. Only stage at diagnosis (HR 3.15; 95% C.I. 2.02-4.92) and PS (HR 2.0; 95% C.I. 1.16-3.44) were prognostic. Median OS (mOS) was 26.8 months (95% C.I. 24.1-29.5). Among patients with exon 19 deletion, OS trended to be longer for pts that started chemotherapy first (HR 0.50; 95% C.I. 0.24-1.019, p = 0.056). For patients with L858R, the opposite trend was seen (HR 2.24; 95% C.I. 0.89-5.67, p = 0.088). Interaction of first treatment and mutation type was not significant. Patients ≥ 72 y were unlikely to receive chemotherapy first (p = 0.009). Conclusions: Type of EGFR mutation was neither prognostic nor predictive for OS in this cohort, but may influence the most effective treatment sequence. Further studies are required. All patients TKI first Chemotherapy first N (%) mOS (months, 95% C.I.) N mOS (months, 95% C.I.) N mOS (months, 95% C.I.) All pts 287 (100) 26.8 (24.4-29.2) 237 26.6 (23.2-29.9) 50 37.1 (14.9-59.3) Deletion 19 157 (55) 27.0 (25.4-28.5) 136 27.0 (23.7-30.2) 21 37.1 (7.7-66.5) L858R 67 (23) 24.3 (17.8-30.7) 57 26.7 (20.7-32.7) 10 19.5 (8.1-30.9) Other 10 (3.5) 14.7 (0-39.9) 8 25.6 (4.5-46.7) 2 2.56 (-_) Unknown 53 (18.5) 27.2 (14.6-39.8) 36 17.6 (9.7-25.6) 17 47.8 (21.4-74.2)
PD-L1 expression, immune cell correlates, and PD-1+ lymphocytes in sentinel lymph node positive melanoma patients: Implications for adjuvant PD-1 clinical trials.
Authors: Hojabr Kakavand, Ricardo Vilain, James S Wilmott, Hazel Burke, Jennifer Yearley, John F Thompson, Peter Hersey, Georgina V. Long, Richard A Scolyer
Journal: Journal of Clinical Oncology (2015)

e20011 Background: Patients with positive sentinel lymph node biopsies (SLNB) that undergo a completion lymphadenectomy have variable five-year survival rates ranging from 39-70%. PD-1 and PD-L1 inhibitors have significantly improved recurrence free (RFS) and overall survival (OS) in AJCC stage IIIC/IV metastatic melanoma patients. The aims of this study were to characterise subpopulations of lymphocytes that interact with metastatic melanoma cells in SLNB, to determine tumoral PD-L1 expression and to identify whether the PD-1/PD-L1 pathway contributes to immune escape in these patients to provide a rationale for the use of anti-PD-1 inhibitors in the adjuvant setting and aid in the selection of patients for this treatment modality. Methods: The metastatic melanoma containing SLNB’s from sixty treatment-naive patients were analysed for CD3, CD4, CD8, FOXP3, PD-1, and PD-L1 and correlated clinico-pathologic features and outcome. Results: Tumoral PD-L1 expression ( ≥ 1%-cutoff) was present in 43.3% (n = 26) cases. Cox proportional hazard analysis showed a positive correlation between intratumoral CD3+ lymphocytes and RFS/OS (cutoff > 39.5,HR = 0.36(0.17-0.76),p = 0.005;HR = 0.29(0.14-0.61),p = 0.0005,respectively), a positive correlation between intratumoral CD4+ lymphocytes and RFS/OS (cutoff > 24,HR = 0.34(0.15-0.77),p = 0.007;HR = 0.32(0.14-0.74),p = 0.005,respectively) and a positive correlation between intratumoral CD8+ lymphocytes and RFS/OS (cutoff > 29,HR = 0.42(0.21-0.85),p = 0.013;HR = 0.32(0.19-0.78),p = 0.006respectively) in our cohort of patients. There was a negative correlation between peritumoral PD-1+ lymphocytes and RFS/OS (cutoff > 1.5,HR = 2.67(1.17-6.13),p = 0.016;HR = 2.74(1.14-6.76),p = 0.019respectively). Conclusions: Expression of PD-L1 in metastatic melanoma-positive SLNB’s provides a rationale for trials of anti-PD-1 therapy in AJCC stage IIIA melanoma patients, particularly those with peritumoral PD-1+ lymphocytes. The expression of immune markers may also be useful to predict the outcome of patients following a positive SNLB.
Cancer costs and trends for newly diagnosed malignancies at an academic institution.
Authors: Stephanie Purkat Lindauer, Barbara Hinojosa, Jessica Trevino Jones, Marcela Mazo- Canola, Jonathan Gelfond, Kate Ida Lathrop
Journal: Journal of Clinical Oncology (2017)

8 Background: The financial cost of cancer is a large burden and continues to rise substantially. Expenditures can be divided into the initial phase after diagnosis, the continuing phase, and the last year of life. Typically costs are greatest in the initial phase and last year of life. The major determinant of cost during the initial phase is hospitalizations. We sought to examine cancer costs of patients with newly diagnosed malignancies at an academic institution during the initial phase and compare outcomes based on insurance status. Our institution serves a significant portion of South Texas, a population facing serious cancer health disparities. Methods: This was a prospective, non-randomized study evaluating patients with new cancer diagnoses from 2014-2016 at an academic hospital. Patients meeting eligibility criteria were screened and consented for participation. A total of 74 patients were included in analysis. Results: The average age was similar in both the self-pay group and the insurance group (including government-sponsored, private, and county funding); 51.1 vs 54.8 years respectively (p = 0.09). Ethnicity between the two groups was not significantly different, 46.2% were Hispanic in the self-pay group vs 45.8% in the insurance group (p = 0.94). The majority of patients in both groups presented with advanced disease, 61.5% in the self-pay group vs 70.8% in the insurance group (p = 0.44). The average number of days of hospitalization was significantly higher in the insurance group compared to the self-pay group, 15.4 days vs 10.6 (p = 0.04). Congruently, average total cost of hospitalization was higher in the insurance group, $96,200 vs $64,200 (p = 0.05). 26.9% of patients in the self-pay group enrolled in hospice within 6 months of their diagnosis vs 20.8% in the insurance group (p = 0.26). Conclusions: With the limitation of a small sample size, our study demonstrates a statistically significant difference in hospitalization days and cost in insured vs uninsured patients with new cancer diagnoses at an academic hospital.
Independent validation of progression-free survival rate at 9 and 18 weeks (PFSR-18, PFSR-9) as predictor for overall survival (OS) in patients with malignant pleural mesothelioma (MPM): EORTC 08052 study.
Authors: Baktiar Hasan, Athanasios G. Pallis, Rabab Mohamed Gaafar, Laurent Greillier, Jan P. Van Meerbeeck, Mary O'Brien
Journal: Journal of Clinical Oncology (2013)

7584 Background: The increasing incidence and the plateau of current treatment outcomes in MPM necessitates development of new therapeutic approaches. Reliable and meaningful response assessment is difficult in phase II trials thus a primary endpoint based on progression free survival (PFS) rate at certain time point has been proposed (Greillier et al, 2011). EORTC 08052 was a phase II study in MPM where independent validation of PFSR-18 weeks was foreseen. We extend this to PFSR-9. Methods: Association of PFS and response with OS was assessed at two distinct time points; 9 and 18 weeks after registration. Landmarks method was used, PFS status (CR/PR/SD vs. PD) and response status (CR/PR vs. PD/SD) were determined at those time points. Cox regression and logrank test were performed and the corresponding c-indexes were calculated. Results: Of 82 registered patients, 28.4% achieved CR/PR and 77.8% had disease control (CR/PR/SD) as their best overall response. PFSR-18 and PFSR-9 were both strongly correlated with OS. Patients with no progression at 18 weeks had median OS of 16.9 months compared to 11.9 months in those who progressed at 18 weeks. Hazard ratio [HR] (95 confidence interval [CI]) was 0.46 (0.32-0.67), logrank test was 0.007 and C-index = 0.60. Adjusting for 3 important baseline prognosis factors, histology, performance status and disease stage resulted in PFS-18 as the only significant factor. When 9 weeks landmark was chosen, patients with no progression had median OS of 16.9 months vs. 6.8 months in those who progressed with HR (CI), logrank test and C-index 0.35(0.25-0.49), &lt; 0.0001 and 0.66 respectively. When adjusted by 3 important baseline prognosis factors PFS-9 remained the only significant factor. The results also confirmed that response at 18 weeks and 9 weeks was correlated with OS. Conclusions: PFSR-18 was strongly correlated and discriminated patients with better OS from the poorer prognosis patients. An earlier endpoint, PFSR-9 was also strongly correlated to OS and had a better discriminating capacity. Previous results on correlation between PFSR-9 and PFSR-18 and OS were independently validated.
Association of decreased expressions of α1,6-fucosyltransferase (α1,6-FT), GDP-mannose-4,6-dehydratase (GMD), and GDP-fucose transporter (GDP-Fuc Tr) with squamous histology in non-small cell lung cancers (NSCLCs).
Authors: Rio Honma, Ichiro Kinoshita, Eiji Miyoshi, Yoshihiro Matsuno, Yasushi Shimizu, Kichizo Kaga, Naoyuki Taniguchi, Hirotoshi Akita
Journal: Journal of Clinical Oncology (2012)

e17520 Background: α1,6-FT, a key enzyme for the core fucosylation of N-glycans, has been shown to be needed for the function of EGF and TGF-β1 receptors. α1,6-FT expression is found in human normal bronchial epithelial cells and bronchial gland cells. However, α1,6-FT expression has not been previously examined in NSCLCs. GMD generates GDP-fucose from GDP-mannose, and is imperative for the synthesis of all fucosylated oligosaccharides. GDP-fucose is transported into the Golgi apparatus by GDP-Fuc Tr to serve as a substrate of FTs. Methods: We examined expressions of α1,6-FT, GMD and GDP-Fuc Tr by immunohistochemistry in 156 surgically resected NSCLCs. Results: High, moderate and low expression of α1,6-FT was found in 25 (16.0%), 35 (22.4%) and 96 (61.6%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between α1,6-FT expression and various characteristics revealed a significant association between low α1,6-FT expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.0005; low vs. high, p = 0.005). High, moderate and low expression of GMD was found in 32 (20.5%), 32 (20.5%) and 92 (59.0%) NSCLCs, respectively. Multivariate logistic regression analysis for the correlation between GMD expression and various characteristics revealed a significant association between low GMD expression and squamous cell carcinomas, as compared with non-squamous cell carcinomas (low vs. moderate, p = 0.005; low vs. high, p = 0.02). Low expression of α1,6-FT was more prevalent in tumors with low GMD expression than in those with moderate or high GMD expression (p = 0.002). High/moderate, low and no expression of GDP-Fuc Tr was found in 7 (4.5%), 23 (14.7%) and 126 (80.8%) NSCLCs, respectively. Low GDP-Fuc Tr expression was significantly more prevalent in squamous cell carcinomas compared with non-squamous cell carcinomas (p = 0.003). Conclusions: These results indicate that α1,6-FT, GMD and GDP-Fuc Tr may be new markers of NSCLCs with specificity for histology.
Patient and provider perspective on financial burden after an allogeneic hematopoietic cell transplantation.
Authors: Sunny Wonsun Kim, Gregory Alan Abel, Julie McNulty, Mary Weise, Diana Salas Coronado, Shahrukh Hashmi, Vivek Roy, Jon Charles Tilburt, Randy Albelda, Nandita Khera
Journal: Journal of Clinical Oncology (2014)

e17539 Background: Although the economic impact of allogeneic hematopoietic cell transplantation (HCT) on the health care system has been described, little is known about the financial consequences for patients. We utilized 2 data sources to assess the perceptions of patients and providers about the financial burden for patients. Methods: For patient perspective, a 25 item questionnaire was mailed to 482 allogeneic HCT recipients transplanted from 1/06 to 6/12 at the Mayo Clinic to collect socioeconomic and financial burden information including an open-ended question: ‘how has transplant made an impact on your financial situation’. A constant comparative analysis of the narrative comments by 79 of 268 respondents was done and themes were compared with the themes from a focus group of 10 HCT social workers/ nurses at the Dana Farber Cancer Institute, formed to explore perceptions of patients’ concerns. Results: Patients and providers described specific concerns such as inadequate pre HCT communication/ preparation for financial burden, caregiver stress and importance of support like good insurance and assistance from non-profit organizations. Dichotomies such as ‘painful but worth it’ and ‘grateful to be alive yet HCT created a financial strain’ were apparent. While the patients worried about lifetime costs and loss of home/ business, providers stressed poor pre-HCT finances, non-medical costs/ costs not covered by insurance and wage loss as factors for increasing burden. (Table) Conclusions: Both patients and providers recognize financial distress as a predominant concern post HCT.Future research should consider both perspectives to design interventions to help patients plan optimally to avoid catastrophic financial outcomes. Narrative comments. Patient Provider Medical coverage good, but other things add up (e.g., gas, childcare, time of work) Patients stop getting care because it really is burdensome, expensive, and awful Had to short sale our home of 29 years People circle back for ongoing complications, which means spouses often have to take more time off Post-transplant issues limits what and how much I can do; earning ability is really depleted Insurance is a huge driver in terms of financial burden
Trends in antineoplastic receipt after Medicare payment reform: Implications for future oncology payment design.
Authors: Helen M. Parsons, Susanne Schmidt, Amy J. Davidoff, Laura LaNiel Tenner, Beth A. Virnig
Journal: Journal of Clinical Oncology (2015)

6513 Background: The Medicare Modernization Act (MMA) changed antineoplastic reimbursement from average wholesale price to average sales price +6%, reducing many outpatient reimbursement rates and altering practice patterns for lung cancer. To further evaluate the MMA’s effect, we focus on colon cancer, where longstanding fluorouracil-based regimens were augmented in 2004 with 3 newly-approved drugs (oxaliplatin, bevacizumab, and/or cetuximab). Methods: Using the 2000-2009 SEER-Medicare data, we examined trends in chemotherapy use and type of antineoplastic received among 59,642 stages II-IV colon cancer patients. Logistic regression models tested the effect of time (pre-post the 2005-2006 reimbursement change) and setting (physician offices implemented reimbursement changes in 2005 vs hospital outpatient departments (OPD) in 2006); interaction terms tested for differential effects of MMA implementation in the 2 settings. Models controlled for patient demographic and tumor characteristics. Results: Overall, 16.3% of stage II, 52.4% stage III and 39.6% stage IV colon cancer patients received antineoplastics. After the reimbursement change in 2007-09 relative to 2000-03, stages II (marginal probability (MP) = -0.06, p < 0.01) and III (MP = -0.04, p < 0.01) patients decreased antineoplastic use, while stage IV patients increased use (MP = 0.03, p < 0.01). While use of fluorouracil-based therapy decreased slightly after reimbursement changes (MP:-0.07 stage II; -0.04 stage III; -0.04 stage IV; p < 0.01 for all), use of new drugs increased substantially (MP: 0.47 stage II; 0.67 stage III, 0.77 stage IV; p < 0.01 for all). Use of new drugs for stage IV cancer occurred earlier in physician offices compared to OPDs (p < 0.01). Conclusions: Colon cancer patients saw small decreases in treatment with fluorouracil-based chemotherapy, but large increases in newly approved drugs after the MMA. Trends suggest slightly earlier increases in physician office settings for stage IV patients, consistent with an MMA effect. The identifiable effects of the MMA are relatively small, but highlight the responsiveness of providers to changes in reimbursement, and the need to integrate new drugs into payment schema.
3D-microdevice for the in vivo capture of cancer-associated circulating cells.
Authors: Hélène Cayron, Alejandro Kayum Jiménez Zenteno, Aurore Esteve, Sylvain Sanson, Christophe Vieu, Bernard Andre Malavaud, Aline Cerf
Journal: Journal of Clinical Oncology (2017)

e579 Background: Circulating tumor cells (CTCs) are cancer cells that have detached from a tumor and have entered into the blood circulation at a very low concentration (D. Shook, Mech. Dev., Nov 2003). CTCs have a strong prognostic value, as their number has been correlated to overall survival in different metastatic cancers (J. S. de Bono, Clin. Cancer Res., Oct 2008). Considering the rareness of CTCs in blood, capturing them in vitro is very challenging. CTCs being mainly larger and less deformable than most of blood cells, ISET was the first system exploiting their physical traits using a filtration membrane to enrich 10mL blood samples (G. Vona, Am. J. Pathol., Jan 2000). However, placing the trapping system directly within the bloodstream would increase the amount of blood screened and ensure no sampling bias. To our knowledge, the only system developed for in vivo capture of CTCs relies on an immunologic detection targeting CTCs with specific epithelial-cell adhesion molecules (N. Saucedo-Zeni, Int. J. Oncol., Oct 2012). The major drawback of this technique is the selection bias induced, given the strong heterogeneity of antigen expression profiles in CTC population as confirmed by several studies. Methods: Our device combines the advantages of in vivo capture and physical trapping of CTCs. A polymeric 3D net-like microdevice is fabricated using a Direct Laser Writing technique (Nanoscribe) and integrated onto a Nitinol guidewire to be introduced into the basilic vein through a routine 20G catheter. To optimize the design, we conducted simulation studies and in vitro assays using a fluidic platform reproducing in vivo conditions. Results: We succeeded in capturing PC3 human prostate cancer cells from 20 mL healthy donor blood spiked with 1,000 PC3 cells in 2 minutes, demonstrating the capability to capture CTCs in conditions close to those found in vivo, in terms of pressure and flow rate and without any additional treatment or dilution of the blood. Conclusions: This device could facilitate treatment personalization and follow-up. Its versatility should render it transposable to the capture of single or clustered CTCs, derived from all types of cancer and, by extension, to other circulating cellular and molecular biomarkers.
Basket Studies: Redefining Clinical Trials in the Era of Genome-Driven Oncology
Authors: Jessica J. Tao, Alison M. Schram, David M. Hyman
Journal: Annual Review of Medicine (2017)

Understanding a tumor's detailed molecular profile has become increasingly necessary to deliver the standard of care for patients with advanced cancer. Innovations in both tumor genomic sequencing technology and the development of drugs that target molecular alterations have fueled recent gains in genome-driven oncology care. "Basket studies," or histology-agnostic clinical trials in genomically selected patients, represent one important research tool to continue making progress in this field. We review key aspects of genome-driven oncology care, including the purpose and utility of basket studies, biostatistical considerations in trial design, genomic knowledgebase development, and patient matching and enrollment models, which are critical for translating our genomic knowledge into clinically meaningful outcomes.
Safety and tolerability of sorafenib for treatment of locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer (RAI-rDTC): Detailed analyses from the phase III DECISION trial.
Authors: Francis P. Worden, Martin Fassnacht, Yuankai Shi, Tatiana Hadjieva, Francoise Bonichon, Ming Gao, Laura Fugazzola, Yuichi Ando, Yasuhisa Hasegawa, Do Joon Park, Christopher Nutting, Steven I. Sherman, Young Kee Shong, Johannes WA Smit, John Woojune Chung, Christian Kappeler, Istvan Molnar, Martin Schlumberger, Marcia S. Brose
Journal: Journal of Clinical Oncology (2014)

6062^ Background: The phase III DECISION trial established that sorafenib treatment improved progression-free survival in RAI-rDTC patients. We report here on the incidence and prevalence of adverse events (AEs) by severity and treatment cycle and the dose modification patterns for patients treated on the DECISION trial. Methods: Patients with locally advanced/metastatic progressive RAI-rDTC were randomized and received sorafenib 400 mg bid po or placebo. AEs were recorded by cycle (C) and by grade (G) during the double-blind treatment period using NCI CTCAE v 3.0 or MedDRA v 15.1. Results: A total of 417 patients were randomized (207 to sorafenib and 210 to placebo). Hand-foot skin reaction (HFSR; 76% any grade/20% grade 3/ - grade 4), rash (50/5/0) and hypertension (41/10/0) tended to occur early in treatment (C1 and C2). G1-G3 HFSR occurred in C1, but was primarily G1 thereafter. Diarrhea (69/5/1) and fatigue (50/5/1) had a relatively constant onset across cycles and were predominantly G1. Weight loss (47/6/-) was primarily G1 and G2 with prevalence of G2 increasing with length of treatment. G1 TSH elevation (>0.5 mU/L) necessitating an increase in thyroxine replacement was observed in 33% of sorafenib patients and 13% of placebo patients. Hypocalcemia (19/6/3) was most likely to first occur in C2. Dose reductions in the sorafenib arm started early (35% of patients in C1 were on a reduced dose then ranged 50-60% thereafter). Dose interruptions were highest in C1 and C2 (37% and 26% of patients with dose interruption, respectively) and was <10% by C5. Most AEs decreased in severity or resolved following dose modification. Treatment discontinuation due to AEs occurred in 19% of sorafenib patients and were relatively evenly distributed after C1 (4% C1 and 0-2% C2-C9); 4% of patients in the placebo arm discontinued due to AEs. Conclusions: The incidence and prevalence patterns of AEs by severity and treatment cycle for RAI-rDTC patients treated with sorafenib demonstrated that the majority of AEs were Grade 1-2, occurred early during the treatment course, and were typically manageable over time. Clinical trial information: NCT 00895674.
Zeta-Chain-Associated Protein Kinase-70 (Zap-70) Promotes Acute Lymphoblastic Leukemia (ALL) Infiltration into the Central Nervous System By Enhancing Chemokine Receptor 7 (CCR7) Expression
Authors: Ameera Alsadeq, Henning Fedders, Steffi Spielberg, Christian Vokuhl, Gunnar Cario, Martin Schrappe, Denis Martin Schewe
Journal: Blood (2015)