tbuckley/cabot-search huggingface dataset:
Preliminary results from the international neoadjuvant melanoma consortium (INMC).
Authors: Alexander M. Menzies, Elisa A. Rozeman, Rodabe Navroze Amaria, Richard A. Scolyer, Michael T. Tetzlaff, Alexander Guminski, Michael A. Davies, Christian U. Blank, Jennifer Ann Wargo, Georgina V. Long
Journal: Journal of Clinical Oncology (2017)

9581 Background: For several cancers, response to neoadjuvant therapy (NAT) correlates with survival. Targeted and immune therapies achieve high response rates and durable survival in many patients with metastatic melanoma. Their role as NAT for stage III disease is not clear, and whether pathological response following NAT correlates with relapse-free (RFS) or overall survival (OS) in melanoma is unknown. Methods: Pooled clinical data from four ongoing NAT clinical trials (NCT02437279, NCT02231775, NCT02519322, NCT01972347) at three large melanoma centers participating in the INMC were examined. All trials included only patients with surgically resectable clinical stage III melanoma. NAT regimens included dabrafenib/trametinib (DT) and nivolumab (nivo) [single agent or in combination with ipilimumab (ipi/nivo)]. Patients who had undergone surgery prior to 27 th January 2017 are included in this preliminary analysis. A pathological complete response (pCR) was defined as no viable melanoma cells in the resected specimen by hematoxylin and eosin evaluations by dedicated dermatopathologists. Results: 58 patients with clinical stage III melanoma (AJCCv7: 18 IIIB, 40 IIIC) have completed NAT and undergone surgery. 18 received neoadjuvant immunotherapy (IT): ipi/nivo x2 doses (N = 10), ipi/nivo x3 doses (N = 4) or nivo x4 doses (N = 4). 40 received neoadjuvant DT, either for two (N = 10) or three months (N = 30). Median age is 55 years (range 22-84). A pCR was observed in 50% of patients, 7 (39%) with IT and 22 (55%) with DT. Median follow-up is 10.2 months (95% CI 8.7-12.5). 14 (24%) patients have recurred (5 local, 8 distant, 1 both), 2 (11%) after IT, 12 (30%) after DT. For those with pCR, 14% have recurred, 0/7 (0%) after IT, 4/22 (18%) after DT. In contrast, for those without pCR, 34% have recurred, 2/11 (18%) after IT and 8/18 (44%) after DT. Two deaths have occurred, both after neoadjuvant TT. Early data suggests improved RFS in those with pCR. Conclusions: Neoadjuvant targeted and immunotherapy are active regimens in clinical stage III melanoma patients and are associated with high pCR rate. Preliminary data suggest pCR correlates with improved RFS. Updated data will be presented. Clinical trial information: NCT02437279, NCT02231775, NCT02519322, NCT01972347.
Comparative evaluation of the safety and effectiveness of rivaroxaban (riva) and enoxaparin (enox) for treatment of venous thromboembolism (VTE) in cancer patients.
Authors: Shelly E Hummert, Jeffrey Gilreath, George M Rodgers, Nathan Wilson, David D. Stenehjem
Journal: Journal of Clinical Oncology (2017)

e18268 Background: The current standard for VTE management in patients with active malignancy is low molecular weight heparin (LMWH). Direct oral anticoagulants (DOACs) are convenient options, but comparative data is lacking in cancer patients. Methods: An observational cohort study was conducted to identify patients with cancer treated with either enox or riva (institutional preferences) from December 2012 to April 2015. Patients were excluded if they received prophylactic dosing of enox, prior anticoagulation, transitioned to warfarin, or received anticoagulation for less than 15 days unless they had a bleeding event. Results: A total of 182 patients were included: enox (n = 97) and riva (n = 85). Median age was 65 years at initiation for riva vs 57 years for enox, p = 0.0007. Gender was similar between groups (54% male). Fifty-three percent (n = 97) had metastatic disease and 54% (n = 99) were actively receiving chemotherapy when diagnosed with initial VTE. Sixty-five percent (n = 119) were treated for deep venous thrombosis (DVT), 19 percent (n = 35) had pulmonary embolism (PE), and 11 percent (n = 20) had both DVT and PE. More patients initiated riva for extensive VTE’s 48% vs 29% (p = 0.02). Median duration of anticoagulation was 3.1 months in the enox group and 7.1 months in the riva group (p &lt; 0.0001). Recurrent VTE occurred in 3 patients (one on riva). Ten percent of patients (n = 10) had a bleeding event on enox compared to 15 percent on riva (n = 13, p = 0.3). Major bleeds occurred in seven percent (n = 7) in the enox group and 8 percent (n = 7) in the riva group (p = 0.4). One fatal bleed occurred with each anticoagulant. Pharmacodynamic interactions with antiplatelet agents may have contributed to 3 major bleeds (two with riva). Three percent of patients (n = 3) experienced minor symptomatic bleeds on enox compared to six (7%) on riva. Mean time to bleeding will be presented. Conclusions: Riva is a safe and effective alternative to enox for VTE management in cancer patients. Concomitant medications must be reviewed before initiation and during anticoagulant therapy to minimize drug interactions. Randomized trials are needed to directly compare LMWH to DOACs in this population.
A randomized, double-blind, placebo-controlled, phase II study of regorafenib vs placebo in advanced/metastatic, treatment-refractory liposarcoma: results from the SARC024 study.
Authors: Richard F. Riedel, Karla V. Ballman, Yao Lu, Steven Attia, Elizabeth Trice Loggers, Kristen N. Ganjoo, Michael B. Livingston, Warren Allen Chow, Jennifer A. Wright, John Harris Ward, Daniel A. Rushing, Scott H. Okuno, Damon R. Reed, David A. Liebner, Vicki Leigh Keedy, Leo Mascarenhas, Lara Emily Davis, Christopher W. Ryan, Denise K. Reinke, Robert G. Maki
Journal: Journal of Clinical Oncology (2018)

11505 Background: Pazopanib, a multi-targeted tyrosine kinase inhibitor, has shown activity in various soft tissue sarcomas. Activity in liposarcoma, however, is limited. Regorafenib is a multi-kinase inhibitor with anti-angiogenic properties similar to pazopanib. We conducted a randomized, phase II study of regorafenib (R) vs. placebo (P) in refractory liposarcoma patients (pts). Methods: Pts with advanced/metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg daily or placebo (3 weeks on/1 week off). Pts. with well-differentiated liposarcoma only were excluded. Crossover for placebo pts was allowed upon progression. The primary objective was progression-free survival (PFS) for R vs P. Stratification factors included prior lines of therapy (1 vs 2+) and WHO performance status (0-1 vs 2). The study was powered to detect a difference of ≥ 3 months in median PFS. Secondary objectives included AE assessments, overall response rate (ORR), time to tumor progression (TTP), PFS at 8 and 16 weeks, overall survival (OS), and disease–specific survival (DSS). Results: Forty-eight subjects were enrolled with 47 (27 M: 20 F) having follow-up information. Median follow-up was 3.8 months (0.2-15.3). More women were randomized to R than men (58% vs. 42%; p < 0.03), otherwise baseline characteristics were similar between cohorts. Thirty-three dedifferentiated, 12 myxoid/round cell and 2 pleomorphic liposarcomas were included in the analyses. Most common grade 3-4 AEs observed with R included: grade 3 abdominal pain (13%), hypertension (13%), rash (13%), anemia (8%), anorexia (8%), generalized weakness (8%), and elevated lipase (8%); (grade 4 – none). One grade 5 event occurred in R and 3 in P. Median PFS was 1.9 (0.9-3.7) months for R vs 2.1 (1.6-3.1) months for P; stratified HR 0.87 (0.47, 1.64), p-value = 0.68. No responses were seen in R. One PR was observed in P. Median OS was NR (4.2-NR) for R vs 8.1 (2.9-NR) months for P, stratified p-value = 0.13. Conclusions: Regorafenib did not achieve the primary outcome of improved PFS in treatment-refractory liposarcoma. No new safety signals were observed. Clinical trial information: NCT02048371.
PREDICTOR (UNICANCER GEP11): Randomized phase II study of preoperative afatinib in untreated head and neck squamous cell carcinoma (HNSCC) patients.
Authors: Christophe Le Tourneau, Jean-Pierre Delord, Gilles Dolivet, Olivier Malard, Jérôme Fayette, Olivier Capitain, Caroline Even, Caroline Hoffmann, Sebastien Vergez, Lionnel Geoffrois, Frederic Rolland, Philippe Zrounba, Laurent Laccourreye, Joel Guigay, Ivan Bieche, Jerzy Klijanienko, Nicolas Aide, Valerie Benavent, Jocelyn Gal, Stephane Temam
Journal: Journal of Clinical Oncology (2017)

6021 Background: Afatinib, a pan-HER irreversible tyrosine kinase inhibitor, demonstrated limited antitumor activity compared to methotrexate in unselected recurrent and/or metastatic HNSCC patients (LUX-HN1, Machiels et al, Lancet Oncol 2015). The UNICANCER (GEP 11) PREDICTOR study’s objective was to identify predictive and pharmacodynamic biomarkers of biological activity and efficacy of afatinib (EUDRACT N° 2010-024046-29). Methods: This open-label, randomized, multicentric, controlled, phase II study included untreated patients with operable T2-4N0-2M0 HNSCC of the oral cavity, pharynx and larynx, with a PS &lt; 2, adequate organ function and LVEF &gt; 50%. Patients were randomized (2:1) to: oral afatinib (A) 40mg/day (d) for 14-28d or no treatment (NT). Patients had pre-treatment tumor biopsies, tumor imaging, and PET CT scan, with a 2 nd tumor imaging before surgery and a PET scan at D15. Adverse events were classified by NCI CTCAE criteria. Based on the biological primary endpoint of tumor reduction the sample size was designed to identify biomarkers associated with a 20% difference between the study arms. Results: 61 patients were included (A: 41/NT: 20). 2 patients in the NT arm were not analyzed (consent withdrawal, no surgery). 7 patients in arm A received &lt; 14d of treatment, including 6 patients with unacceptable toxicity. Afatinib-related toxicities were: grade (G)1 37%, G2 41%, G3 7%, G4 5%, and G5 0%. G≥3 toxicities were mainly gastrointestinal. Partial responses (RECIST1.1) were observed in 3 patients (7.3%) in arm A versus none in the NT arm (p = 0.018). Progressive disease was not observed in arm A versus 3 (16.6%) in the NT arm. Partial responses on PET CT scan by PERCIST were observed in 15/31 evaluable patients (48%) in arm A versus 1/15 (6.7%) in the NT arm (p = 0.005). Conclusions: Afatinib given to HNSCC patients in the preoperative setting is safe and is associated with improved response according to RECIST1.1 and PERCIST compared to no treatment. Clinical trial information: NCT01415674.
The relationship between Pim-3 expression and chemoradiotherapy resistance in locally advanced rectal cancer patients.
Authors: Rong-xin Zhang, Zhongguo Zhou, Shi-xun Lu, Zhen-hai LU, Desen Wan, Zhi-zhong Pan, Xiao Jun Wu, Gong Chen
Journal: Journal of Clinical Oncology (2017)

e15112 Background: It is difficult for clinical oncologists to predict which types of rectal cancer patient would respond to neoadjuvant chemoradiotherapy. About 30% of rectal cancer patients who could not benefit from chemoradiotherapy, and about 10% of patients even suffered from disease progression. It is of considerable importance to identify a bio-marker to identify patients who would benefit from neoadjuvant treatment. Methods: This study enrolled 175 rectal cancer patients who underwent neoadjuvant treatment. Tissue samples from all the patients were deposited in the tissue bank of Sun Yat-sen University Cancer Center prior to neoadjuvant treatment. We compared the expression of Pim-3 in rectal tumors and investigated correlations with the response to chemoradiotherapy and with survival. Results: The Pim-3-negative patients were more likely to achieve a pathological complete response to chemoradiotherapy (P = 0.001, RR = 5.132, 95% CI: 2.442–10.787). Cox multivariate analysis in 137 patients with at least 24 months follow-up showed that the expression of Pim-3 (P = 0.041, RR = 1.209, 95% CI = 1.007–1.452) and cycles of neoadjuvant chemotherapy cycles (P = 0.006, RR = 0.557, 95% CI = 0.367–0.845) were significant factors affecting the survival status of patients. Cox multivariate analysis of disease-free survival showed that Pim-3 expression (P = 0.012, RR = 1.180, 95% CI: 1.037–1.344) and adjuvant chemotherapy cycles (P = 0.003, RR = 0.745, 95% CI: 0.615–0.902) were statistically significant factors. Conclusions: Pim-3 could be a potential predictive bio-marker of the response to chemoradiotherapy.
Breast cancer screening guidelines: Is it time to revisit? A survey.
Authors: Archana C. Rao, Srivalli Gopaluni, Sheila M. Lemke
Journal: Journal of Clinical Oncology (2012)

e11089 Background: Breast cancer is the most common non-skin cancer among women in US. In a 2012 report by CDCbreast cancer screening rates are falling short of government targets. At least 10 different societies have laid out screening guidelines, making it difficult to follow. We conducted a survey to better understand adherence to guidelines among health care providers. Methods: A questionnaire comprising of 15 questions was distributed to 120 providers within the Department of Medicine at a University Hospital. Results: 68% returned completed questionnaires: Residents (53%), Attendings/Fellows (36%) and Nurse Practioners/Medical students (11%). Despite 60% respondents claiming that screening guidelines were easy to comprehend and follow; the table suggests otherwise. 49% of the respondents follow United States Preventive Services Task Force guidelines (USPSTF) 28% of these commenced screening at age 40; against the recommendations to start at age 50 and to initiate discussions between the ages of 40-50. 16% of the respondents followed National Comprehensive Cancer Network (NCCN)/American Cancer Society guidelines. 46% of these commenced screening at age 50 or between ages 40-50 contrary to recommendations to begin screening at age 40. Similarly 42% of respondents chose to discontinue screening at the age of 75 in concordance to USPSTF guidelines. 5% chose to screen indefinitely and 1% said they would individualize. 52% did not conform to any guidelines. 69% advocated self breast examinations despite most societies not encouraging the same. Conclusions: While majority of providers follow USPSTF guidelines, there is a considerable discordance between guidelines respondents claim to follow and their practices. This could be attributed to the lack of uniformity in the guidelines across various societies making it harder to comprehend and recall. A unifying consensus would make it easier for providers to improve effective screening. [Table: see text]
Early palliative care interventions in patients with glioblastoma.
Authors: Prakash Ambady, Connor Hambelton, Rongwei (Rochelle) Fu, Jenny Firkins, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2018)

e22203 Background: Glioblastomas (GBMs) are primary malignant brain tumors that, in spite of aggressive treatment, carry a poor prognosis and a significant emotional and socioeconomic burden. Early palliative intervention has been shown to improve quality of life, reduce cost and influence end of life care decisions. We evaluate if early palliative care (PC) referrals alter end of life care in patients with GBM. Methods: After Institutional review board approval, we conducted a retrospective chart review of 44 consecutive patients diagnosed with GBM who received chemo-radiation between 11/2012 and 3/2017. Time from diagnosis to PC referral and number of outpatient PC visits were correlated with multiple variables including number of hospice care days and number of non-elective hospital admissions, using Spearman correlation coefficient. Results: The median age at diagnosis was 60.4 years (range: 20-79, 12 females). Majority (68%) received home hospice. The median number of days on hospice was 29 (range: 0-157), and median outpatient PC visits were 2 (range: 0-25). Although not statistically significant, time from diagnosis to PC referral showed a positive correlation with number of days on hospice, (r = 0.241, p = 0.134), while the number of outpatient PC visits correlated negatively with days on hospice, (r = -0.263, p = 0.088). Number of days of non-elective hospital admissions for symptom management or complications was not correlated with number of PC visits (r = -0.48, p = 0.75) or time to referral (r = 0.0041, p = 0.979). The number of hospice days did not differ by age, performance status at diagnosis and gender of the primary caregiver, either. Only 3 of 44 (7%) patients discussed Death With Dignity (DWD) and only 1 went through the process to obtain the drugs. Conclusions: Although PC may be beneficial from a social and emotional standpoint; early initiation of PC was not associated with the number of non-elective hospital admissions, or number of days on hospice. Our results suggest that early and aggressive PC may provide services that help reduce the number of hospice days and facilitate home hospice. An extremely low number of patients initiated discussion about DWD. A multiple-institution study may be necessary to produce more robust results.
Multivariate analysis on prognostic factors for intrathyroid papillary thyroid carcinoma.
Authors: Ivan Markovic, Merima Goran, Marko Buta, Igor Djurisic, Nevena Petrovic, Andjela Babic, Marko Jevric, Gordana Pupic, Radan Radoslav Dzodic
Journal: Journal of Clinical Oncology (2018)

e18100 Background: The aim of this study was to examine prognostic significance of patient-related, tumor-related and treatment-related factors for intrathyroid papillary thyroid carcinomas (IPTC). Methods: This study included 153 patients with IPTC (pT1-3) surgically treated in one Institution during 18 years. Patients with pT4 tumors and initial distant metastases (M1) were excluded. We have analyzed the following prognostic factors: gender, age (£45; > 45 years), tumor size, multifocality, histological variants of PTC, presence of lymph node metastases, and extent of surgery. Univariate and multivariate analysis of all parameters was performed in order to distinguish prognostic factors for disease-free time (DFT) and cancer-specific survival (CSS). Results: In the median follow-up of 84 months, 10% of patients had locoregional or distant relapse, while 5.2% died due to IPTC. Univariate analysis distinguished older age (p = 0.0001), male gender (p = 0.042), tumors over 4cm in diameter (p = 0.006), multifocality (p = 0.0004) and poorly differentiated IPTC-types (p = 0.0001) as unfavorable prognostic factors for CSS. DFT was significantly shorter in males vs. females (Log Rank = 6.64; p = 0.01), as well as in patients with multifocal vs. solitary PTC (Log Rank = 6.72; p = 0.0095). Tumor multifocality was unfavorable prognostic factor on both DFT and CSS (p = 0.0095and p = 0.0004, respectively). Independent prognostic factors for intrathyroidal PTC, based on Cox multivariate analysis, were multifocality and gender for DFT, and multifocality and age at diagnosis for CSS. Conclusions: Prognostic factors define risk groups within patients with IPTC providing adequate, timely treatment and better DFT and CSS.
High-quality whole-genome sequencing of FFPE samples.
Authors: Shannon Terrell Bailey, Jim Lund, Hao Wang, Hao Chen, Hongye Sun, Jeffery Gulcher
Journal: Journal of Clinical Oncology (2018)

e13500 Background: Next-generation sequencing analysis of formalin-fixed, paraffin-embedded (FFPE) samples has the potential to lead to major advances in cancer treatment and prevention. However, whole-genome sequencing of these samples has remained challenging due to the difficult process of isolating high-quality DNA and distinguishing true variant calls from artifacts. Previous studies have attempted to overcome these challenges by using whole-exome sequencing or smaller exon panels at high coverage depths to analyze FFPE samples. While these approaches have produced useful results, they have had varying degrees of success, tend to have coverage biases due to probe capture issues, and are limited to only a fraction of the genome. Thus, there has not been widespread adoption of using FFPE samples for next-generation sequencing. Methods: In an attempt to improve on the process of next-generation sequencing of FFPE samples, we developed an efficient DNA extraction method that produces high quantities of high-quality DNA. Results: Whole-genome sequencing of DNA generated by our method demonstrates uniformly high coverage that is comparable to DNA prepared from fresh frozen samples at similar sequencing depths. Analyses of mutation calls in these samples reveals a high concordance with those produced from fresh frozen samples. We have used our extraction method to analyze greater than 1,000 tumor-normal pairs of various ages and tumor types. Whole-genome sequencing of DNA generated from our method demonstrate an average of 98% of the genome covered at 20X or greater depth with no difference for the oldest samples examined. Mutational analyses of the different tumor types demonstrate similar findings as that previously published for TCGA datasets. Conclusions: Our analysis of greater than 1,000 samples is the largest study of whole-genome sequencing of DNA extracted from FFPE samples to date. Our results demonstrate the feasibility of using our method to assay tissues stored in archival tissue biobanks, analyze patient samples for clinical trial recruitment, or examining sections as part of normal clinical workflows, all of which hold the potential for greatly benefiting human health.
Relation of depressive and anxious symptoms to overall distress and mortality in patients undergoing radiation therapy.
Authors: Christopher Brett, Gerald Strong, Lauren L. Hintenlang, Dale Alan Whitaker, Niveditha Jagadesh, Robert Clell Miller
Journal: Journal of Clinical Oncology (2017)

e21567 Background: For patients diagnosed with cancer, depression and anxiety represent a common and significant burden, which has been proposed to not only affect quality of life but to potentially shorten duration of life as well. This study examines the influence of patient reported symptoms of anxiety and depression on overall distress and mortality in patients undergoing radiation therapy. Methods: As part of their intake paperwork, patients undergoing radiation therapy completed distress screening that included 29 questions regarding their level of concern with various factors related to their care as well as their overall distress level. This information and other parameters including demographics, site of primary disease, use of chemotherapy, presence of metastasis, and last known status were recorded for analysis. Answers regarding degree of concern for “feeling down or depressed”, “loss of interest in my usual activities”, and “feeling nervous or anxious” were examined for influence on study endpoints. Results: Results for final analysis were available from 519 patients undergoing therapy from April 2010 to May 2016. The cohort’s average age was 66yrs, 71% were treated curatively, and 29% were treated palliatively. The most common treatment sites were breast (27%), thorax (16%), H&amp;N (12%), GU (12%), GI (10%), and CNS (7%). Significant correlation was found between level of concern with symptoms of anxiety and depression and level of overall distress (P &lt; 0.001, Kruskal-Wallis Rank Sum Test). Significance remained on separate analysis of curative and palliative subgroups. No significant correlation was found for 1 or 2 year survival on either single or multivariate analysis of curative or palliative patients. Conclusions: Depression and anxiety are common conditions among cancer patients, and can contribute significantly to their overall distress. Although no effects on mortality were demonstrated on initial follow-up of this cohort, it remains evident that attention to emotional well-being is critical in the care of such patients. Additional investigations can be pursued regarding ideal interventions for patients identified by such screening.
TCT-27 Left ventricular function following higher-risk percutaneous coronary intervention performed with hemodynamic support
Authors: Juan Russo, Darshan Doshi, Dimitrios Karmpaliotis, Manish Parikh, Ziad Ali, E. Magnus Ohman, William O'Neill, Martin Leon, Jeffrey W. Moses, Ajay Jayant Kirtane
Journal: Journal of the American College of Cardiology (2018)