tbuckley/cabot-search huggingface dataset:
Effects of bevacizmab, eribulin and oxaliplatin in relapsed patients with platinum-resistant and refractory ovarian carcinomas: A preliminary case series with biomarker evaluation.
Authors: Jin Suminokura, Hiroko Kouta, Kazuya Kudoh, Miyuki Horikoshi, Tomoyuki Yoshikawa, Hiroko Matsuura, Morikazu Miyamoto, Masashi Takano, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2019)

e17059 Background: Eribulin is a candidate for paclitaxel-refractory breast cancers, and Bevacizmab (B) is known to enhance efficacy of anti-cancer agents in ovarian cancers. A combination therapy using weekly administration of B with eribulin and oxaliplatin (EriOX) in relapsed patients with platinum-resistant and refactory ovarian carcinomas (PR-ROC) was evaluated retrospectively, and the association with response and serum biomarkers was investigated. Methods: Medical charts of the patients who met the criteria shown below were identified: (a) histologically confirmed epithelial ovarian cancer (b) diagnosed as platinum-resistant ovarian cancer (c) treated with weekly-B-EriOX consisting of B (2mg/kg), eribulin (1mg/m 2 ), and oxaliplatin (30mg/m 2 ), three weeks on and one week off, q4weeks (d) written informed consent. Biomarker analyses including serum VEGF, BNP, p53, and IL-6 were also conducted. Results: A total of 34 patients were treated with weekly-B-EriOX. Median age of the patients was 58.5 years (range: 35-76), and median number of previous regimen was 4(range: 2-9). Overall, two patients (6%) had a complete response (CR), 8 patients (24%) had a partial remission (PR) and 16 patients (47%) had a stable disease (SD). The response rate and clinical benefit rate (CR+PR+SD) were 29% and 76%, respectively. Median progression-free survival was 4 months (range: 1-27+). Hematological adverse effects (AE) with grade 3/4 were observed in 4 patients (11%). Non-hematological AE greater than grade 2 was observed in one case: hypo albuminemia and edema, which were manageable and tolerable. The patients with elevation of serum mutated p53 protein and IL-6 had poorer prognosis. Conclusions: Weekly B and EriOX administration showed a remarkable response for patients with PR-ROC. Elevation of serum mutated p53 protein and IL-6 could be biomarkers for this regimen. These results warrant further prospective studies with additional biomarker analyses.
Comprehensive germline panel testing across cancer types: Diagnostic yield and clinical utility in 100,000 patient dataset.
Authors: Shan Yang, Scott T. Michalski, Daniel Esteban Pineda Alvarez, Stephen E Lincoln, Pat W. Whitworth, Robert L. Nussbaum, Edward D. Esplin, Edward D. Esplin
Journal: Journal of Clinical Oncology (2019)

e13013 Background: Over 608,000 patients with ovarian, breast, pancreatic, prostate and colorectal cancer are diagnosed each year. NCCN guidelines recommend offering germline genetic testing to all patients with ovarian and pancreatic cancer, and patients with prostate and breast cancer who meet specific criteria. We present data from ~113,000 patients who were tested on a comprehensive multigene panel and compare the diagnostic yield and clinical actionability with that of a limited gene panel strategy. Methods: We analyzed de-identified sequence data for 83 cancer-risk genes in patients with breast, ovarian, prostate and pancreatic cancer referred for germline genetic testing. Positive rates for a minimal gene panel for the respective indication were computed and compared to the positive rates when the comprehensive 83 gene panel was analyzed. Results: Four percent of 103,428 patients with breast, ovarian, pancreatic and prostate cancer harbored a BRCA1 or BRCA2 germline mutation including: breast 3.7%, ovarian 8.2%, prostate 5.2% and pancreatic 4.2%. When the comprehensive panel is applied, the overall diagnostic yield for all 113,107 patients increased to 16%. Excluding mono-allelic P/LP variants in recessive cancer-risk genes (e.g. MUTYH) reduces the diagnostic yield to 13%. Stratified by cancer type, and removing mono-allelic recessives, positive yield was: breast 11.8%, ovarian 18%, prostate 15%, and pancreatic 16%. Conclusions: These data show that comprehensive panel testing in patients with a broad range of cancers more than doubles the diagnostic yield, providing actionable results for an additional 9,737 per 113,107 patients tested. Potential germline-based clinical actionability for these patients includes: 1) pan-cancer eligibility for PARP inhibitor clinical trials, 2) FDA approved PD1 blockade for advanced cancer of ANY type and a molecular diagnosis of Lynch syndrome, 3) cascade family variant testing.This study suggests that genetic testing guidelines should be expanded to include recommendations supporting multigene panel testing in patients with cancer to improve the care of patients and their family members.
Preoperative CA 19-9 and CEA as predictors of operative outcomes in resectable gastric cancer (GC).
Authors: Alexandra Gangi, John David, Michelle Guan, Veronica Placencio-Hickok, Andrew Eugene Hendifar, Samuel Jacob Klempner, Miguel Burch, Joseph Chao, Mitchell Kamrava, Richard Tuli, Jun Gong
Journal: Journal of Clinical Oncology (2019)

e15581 Background: We sought to investigate whether preoperative serum CA 19-9 and CEA levels are predictive of resectability, postoperative outcomes, and survival in resectable GC. Methods: The National Cancer Database (NCDB) was interrogated to identify resectable GC patients between 2004-2015. Gastric adenocarcinoma cases without M1 disease and who did or did not undergo definitive surgery were included. Pretreatment CA 19-9 and CEA levels were classified as high (≥98 U/mL) or low ( &lt; 98 U/mL). Proportions of categorical variables were compared using the Chi-squared test (two-tailed). Hazard ratios (HRs) for overall survival (OS) were compared using multivariate Cox regression, adjusting for baseline demographic and clinical variables. Results: From 183,204 GC cases screened, a final 5,447 patients were available. Resection rates for patients with low (n = 1920) and high (n = 294) CA 19-9 were 69.2% and 40.8% (χ² 90.6, p &lt; 0.00001). 69.6% were resectable with low CEA (n = 5044) and 35.1% were resectable with high CEA (n = 97, χ² 53.0, p &lt; 0.00001). Mortality within 30 days of definitive surgery was 7.5% and 0% in those with high (n = 120) and low CA 19-9 (n = 1286, χ² 85.6, p &lt; 0.00001). There was no significant difference between 30-day mortality across high and low CEA and between 30-day readmission rates across high and low CA 19-9 and CEA levels. Age, median income, high school graduation rate, Charlson comorbidity index, and AJCC clinical N stage all significantly correlated with OS in this cohort. Compared to low preoperative CA 19-9, high CA 19-9 was significantly associated with worse OS (HR 1.24, 95% confidence interval (CI) 1.13-1.37, p &lt; 0.0001). Similarly, a high CEA correlated with worse OS compared to low CEA (HR 1.44, 95% CI 1.32-1.57, p &lt; 0.0001). Conclusions: High preoperative CA 19-9 and CEA are associated wither lower resection rates and worse OS in resectable GC. CA 19-9 but not CEA level predicts for 30-day mortality. Prospective validation is warranted.
Racial and ethnic disparities in clinical presentation and prognosis of conjunctival cancer.
Authors: Yang Zhang, Sarah J Aurit, Omofolasade Kosoko-Lasaki
Journal: Journal of Clinical Oncology (2019)

e13086 Background: To investigate racial and epidemiological disparities in presentation and prognosis of conjunctival cancer in a retrospective population-based study. Methods: Non-Hispanic white (NHW) and African American patients with squamous cell carcinoma or melanoma of the conjunctiva or cornea with known age, insurance, gender, zip code-level income and education, and tumor size were selected from the National Cancer Database (NCDB). Patients were stratified based on race and ethnicity into two mutually exclusive groups, and unadjusted comparisons were made with the Chi-square or Mann-Whitney tests. Survival was examined with the Kaplan-Meier method and a Cox regression model was employed after checking that the proportional hazards assumption was met for all pertinent variables. SAS version 9.4 was used for all analyses and p&lt; 0.05 was considered significant. Results: Of the 2,192 identified patients from 2004 to 2014, 104 were African American. Unadjusted differences were found between groups in regard to age, histology, insurance, income, and education. African American patients in comparison to NHW were younger (median age: 61 years vs. 71 years; p&lt; 0.001), had a higher proportion of Medicaid (10.6% vs. 3.4%) or no insurance (11.5% vs. 2.7%), and resided in areas with lower levels of education (36.5% of African American patients vs. 17.0% of NHW patients were from areas with greater than 21% of the population with no high school degree). It was also found that African Americans had higher proportion of squamous cell carcinoma than NHW (69.9% vs. 81.7%; p= 0.007). In general, risk of death was higher for older African American males with no private insurance, and for those from areas of lowest level of income. Conclusions: Disparities in socioeconomic factors were observed in the African American population. In addition, the overall incidence of conjunctival and corneal cancer occurs at a younger age in African Americans, who also face poorer prognoses. This association between social inequality and poor outcome warrant further investigation.
Personalized T cell therapy for metastatic colon cancer.
Authors: Sruthi Ravindranathan, Mohammad Raheel Jajja, Alexandra Waller, Ramireddy Bommireddy, Christopher Petersen, Periasamy Selvaraj, Lily Yang, Gregory B. Lesinski, Bassel F. El-Rayes, Brianna Flynn, Edmund K. Waller
Journal: Journal of Clinical Oncology (2019)

e15183 Background: Current immunotherapies fail to benefit patients with colon cancer, largely due to high molecular heterogeneity and low frequencies of tumor infiltrating lymphocytes. In this study, we are addressing this limitation via a novel technology to expand patient tumor specific T cells ex-vivo, using patient’s matched tumor and peripheral blood mononuclear cells (PBMCs). This technology utilizes tumor membrane vesicles (TMVs) made from excised tumor tissue, as a source of tumor associated antigens, and further modified to express IL-12 and B7-1 for ex-vivo expansion of tumor specific T cells. Additionally, the T cells are cultured with PI3K delta inhibitor (idelalisib) and vasoactive intestinal peptide antagonist (VIPhyb) to increase yield, polyfunctionality and in-vivo persistence. Methods: Matched tumor and blood were collected from consented colon cancer patients. TMVs were prepared from excised tumors by homogenizing and centrifuging the tumor over a sucrose gradient. TMVs were then made to express glycosyl phosphatidylinositol (GPI) linked IL-12 and B7-1 (decorated TMV) via a proprietary protein transfer technology. PBMCs isolated from matched blood were cultured in media with 10ug/ml decorated TMV with/without VIPhyb(3uM) and idelalisib (100nM) for 14 days. T cells were then phenotyped for percentage of IFN gamma secreting CD4+ and CD8+ T cells and injected into PDX mice bearing matched tumors (2 doses of 1 million and 4 million cells, 20 days apart). Results: 14 days after expansion, T cells expanded with decorated TMVs+VIPhyb+idelalisib (TMVs+drugs) resulted in significantly increased number of IFN gamma secreting CD8+ T cells (25% of T cells), when compared to T cells treated with decorated TMVs without VIPhyb and idelalisib (13% of T cells). Further, when injected to PDX mice bearing matched tumors, and followed for differences in tumor growth, we observed that on day 30 after T cell injection, while the tumor volumes increased 4.5-fold in the untreated group, the tumors in the TMVs+drugs group only increased 2.8-fold. Conclusions: In this study, we have thus developed a novel technology to expand patient tumor specific T cells ex-vivo, for adoptive T cell therapy against metastatic colon cancer.
Clinical practice patterns on the use of adjuvant bisphosphonate for early breast cancer: A Canadian perspective.
Authors: Lara Zibdawi, Demetrios Simos, Shaqil Kassam, Amira Rana, Farrah Kassam, Yasmin Rahim
Journal: Journal of Clinical Oncology (2019)

e12002 Background: Adjuvant bisphosphonates (ABPs) in menopausal women with early breast cancer (EBC) decrease the risk of BC relapse and modestly improve overall survival (OS). In the era of personalized medicine, a one size fits all approach is not ideal–it is important to identify the subgroup of patients who may not derive a clinically meaningful benefit to avoid over treatment, unnecessary toxicity, and optimize resource utilization. Objectives: To better characterize how Canadian medical oncologists (MOs) use ABPs and whether practice patterns are concordant with the CCO/ASCO guideline. Methods: A brief survey was circulated by e-mail to 618 Canadian MOs between Nov 2017 - May 2018. Questions were designed to gather data on demographics, patient selection, choice of bisphosphonate, schedule/duration of treatment and barriers to use. No incentive was provided. Results: Sixty-eight MOs from 8 Canadian provinces completed the survey (response rate 11.0%). Most practiced in Ontario (65.7%) and just over half (51.5%) were community oncologists. MOs offered ABPs to 52.2% of menopausal women with EBC. Use was higher in the community compared to the academic setting (p=0.049). Most used zoledronic acid (85.3%) every 6 months (95.6%) for 3 years (69.1%) and started treatment within 3 months of completing adjuvant chemotherapy/radiation (67.7%). Factors associated with use of ABPs were: high Oncotype Dx score (89.1%), high tumor grade (72.1%), triple negative disease (63.6%), osteoporosis (87.7%)/osteopenia (83.9%) and use of aromatase Inhibitor (75.0%). The most common factor precluding use of ABPs was presence of comorbidities (89.7%). About 1/3 rd indicated they would offer ABPs to women with stage I HR positive/Her2 negative EBC. Conclusions: Canadian MOs have added intravenous ABPs to their armamentarium of therapies in keeping with the spirit of the recent guideline. High-risk disease features and low bone density appear to be influencing the decision-making process. Further work aimed at identifying those patients who are unlikely to benefit from treatment is needed.
Corrigendum to “DOX/IL-2/IFN-γ co-loaded thermo-sensitive polypeptide hydrogel for efficient melanoma treatment” [Bioact. Mater. 3 (2018) 118–128]
Authors: Qiang Lv, Chaoliang He, Fenli Quan, Shuangjiang Yu, Xuesi Chen
Journal: Bioactive Materials (2019)

[This corrects the article DOI: 10.1016/j.bioactmat.2017.08.003.].
Prediction of distant melanoma recurrence from primary tumor digital H&amp;E images using deep learning.
Authors: Eric Robinson, Prathamesh M. Kulkarni, Jaya Sarin Pradhan, Robyn Denise Gartrell, Chen Yang, Emanuelle M. Rizk, Balazs Acs, Bethany Rohr, Robert Phelps, Tammie Ferringer, Basil Horst, David L. Rimm, Jing Wang, Yvonne M. Saenger
Journal: Journal of Clinical Oncology (2019)

9577 Background: Patients with resected melanoma are at high risk for systemic recurrence. Quantifying the risk of recurrence can help identify the need for adjuvant immunotherapies, and accelerate the acquisition of survival statistics in clinical trials. Methods: 75 patients with stages I, II, and III melanoma seen at Columbia University Medical Center between 2001 and 2014 and The Icahn School of Medicine at Mount Sinai between 2000 and 2010 were included based on availability of tissue and 24 months of clinical follow-up. Images were scanned into tiff files (Aperio Biosystems). Deep neural net (DNN) architecture was designed consisting of convolutional and recurrent neural networks (CNN, RNN). Using QuPath open source software for nuclear segmentation and cell classification, we generated cell location, density, and clustering features to identify tissue areas for training of network parameters. DNN analyzes image and feature information locally within an H&amp;E image, generating a prediction vote per region, and votes are averaged. Results: The model was validated on two independent external sets of stage I-III primary melanomas. Cohort 1 (Yale Medical Center), had n = 86 patients, of whom 49 were alive or had no evidence of disease at death (no DMR) and 37 died from melanoma. The second set, Cohort 2 (Geisnger Health Systems), had n = 29 patients, 15 without DMR and 14 with DMR. Prediction scores correlated with DMR status in both sets (AUC = 0.94 and 0.77 for Cohorts 1 and 2, respectively). A multivariable Cox proportional hazard model showed DNN recurrence prediction to be an independent prognostic factor for both Cohort 1 (HR = 2.54, 95% CI: 1.54-4.19, p = .0004***) and Cohort 2 (HR = 8.43, 95% CI: 2.58-27.51, p = .001**). Conclusions: We designed a DNN for quantitative prediction of melanoma recurrence from a H&amp;E stained tissue. The prediction score warrants further study in larger patient cohorts and may constitute a novel digital pathology tool for the selection of melanoma patients for adjuvant immunotherapy. [Table: see text]
Molecular profile of early-stage and advanced-stage of renal cell cancer in China.
Authors: Jimin Chen, Yanrui Zhang, Tongtong Yang, Huina Wang, Jing Guo, Xiayuan Liang, Feng Lou, Shanbo Cao, Chuanjun Du
Journal: Journal of Clinical Oncology (2019)

e16071 Background: The mutation spectrum has been extensively studied in Renal Cell Cancer (RCC), a heterogeneous disease. While major investigations have focused on metastatic RCC (mRCC). This study intended to explore the molecular characteristics between early-stage (stage I/Ⅱ) and advanced-stage (Ⅲ/Ⅳ) of RCC patients (pts). Methods: 36 tumor specimens were obtained from individual pts diagnosed RCC, including 22 tissues paired with blood samples. Somatic mutations were identified via targeted next generation sequencing with Acornmed panel including 808 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and chromosomal rearrangements. Clinical data of a cohort from TCGA who had RCC was collected and analyzed. Results: Among the 36 pts enrolled, 61% were early-stage group and 39% were advanced-stage group. The most frequently mutated genes in RCC were VHL (50%), PBRM1 (14%), BAP1 (11%), TP53 (11%) and PIK3CA (6%). Truncating mutations were the most frequent alterations accounting for 66% (33/50) of genetic alterations. Mutations in VHL, BAP1, PBRM1 and TP53 were shared by both early and advanced RCC. While mutations in PIK3CA, CDKN2C, EGFR, FAMCA, GRIN2A, KDM6A, SOX17, TSC1 and APC were only detected in early stage group. KNSTRN, KRAS, MYD88, NF2, ATM, PTEN and STAT5B mutations were only detected in advanced group. Among 22 plasma samples, genomic alterations were detected in 40.9% (9/22) of pts postoperatively, such as TP53, PIK3CA, PTEN, and APC. Functional annotation clustering revealed that 4/9 in these genes were tumor suppressors, which negatively regulated apoptosis. Pts with genomic alterations in TP53 (p = 0.0034), PIK3CA (p = 0.0015) or PTEN (p = 0.00017) had worse OS significantly (TCGA). Conclusions: VHL, PBRM1, BAP1 were the most important driver genes mainly detected in all stages of RCC. The heterogeneity between early and advanced-stage may be related with clinical status. Gene alterations in plasma ctDNA postoperatively should have the potential to stratify patients with different prognostic outcome.
Is surgical axillary staging necessary in women with T1 breast cancer who are treated with breast‐conserving therapy?
Authors: Jin Wang, Hailin Tang, Xing Li, Cailu Song, Zhenchong Xiong, Xi Wang, Xiaoming Xie, Jun Tang
Journal: Cancer Communications (2019)

Abstract Background In the post‐Z0011 trial era, the need to perform surgical axillary staging for early‐stage breast cancer patients, who are treated with breast‐conserving therapy (BCT), is being questioned. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the safety of waiving surgical axillary staging in patients with T1 breast cancer treated with BCT. Methods A total of 166,615 eligible patients diagnosed between 2000 and 2012 were divided into staging (sentinel lymph node biopsy or axillary lymph node dissection) and non‐staging (no lymph node examined or only needle aspiration biopsy of lymph nodes) groups. Propensity score matching (PSM) was performed to balance disparities between the two groups. Multivariate analysis with the Cox proportional hazards model was used to assess factors related to breast cancer‐specific survival (BCSS). Results Although the tumor size at time of presentation was decreasing over years, the rate of surgical axillary staging increased from 93.3% to 96.9%. The 5‐year BCSS rates of the whole cohort (before PSM) and matched cohort (after PSM) were 98.0% and 97.5%. Within the matched cohort, the BCSS was significantly longer in the staging group than in the non‐staging group ( P &lt; 0.001). However, surgical axillary staging did not benefit patients who were 50–79 years old, had tumor size &lt; 1 cm, histological grade I disease, or favorable histological types (tubular/mucinous/papillary) in stratified analyses ( P &gt; 0.05). Race, marital status, hormone receptors, and chemotherapy were not associated with the favorable impact of surgical axillary staging on BCSS ( P &gt; 0.05). Conclusion Although surgical axillary staging remains important for T1 breast cancer patients treated with BCT, it might be unnecessary for patients with old age, small tumor, grade I disease, or favorable histological types.
Spiritual and psychological distress in older and the oldest-old living with advanced cancer patients (O-OOAdCa) in a comprehensive cancer center.
Authors: Marvin Omar Delgado-Guay, Maxine Grace Jaucian De La Cruz, Linda Pang, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

e23041 Background: Older adults living with cancer may experience multiple physical, emotional and spiritual symptoms. Limited literature describing the frequency of psychological and spiritual distress in O-OOAdCa. Methods: Retrospective chart review of patients seen by the Palliative Care team from January 2013 to December 2016. We randomly sampled 200 patients aged &lt; 65, 200 patients aged 65 - &lt; 85) and 41 consecutive patients ≥85). Using the ESAS-FS, determined the frequency, and correlates of self-reported Spiritual Pain (SP) and Anxiety (Anx) and Depression (Dep) among these patients. Psycho-spiritual distress was defined as the presence of SP ≥1/10, Anx ≥2/10, and Dep ≥2/10. Results: 52% were female, 61% white, and 48% with ECOG of 2 in the group &lt; 65, 48% were female, 61% white, and 43% an ECOG of 2 from group 65 to 84, and 49% were female, and 83% white, and 49% an ECOG of 3 from the group &gt; 85 years. Spiritual Pain was present in 101/200 (51%) in the group &lt; 65 vs. 61/187 (36%) in group 65-84 vs. 15/54 (29%) in ≥85, p = 0.004. Anxiety was present in 130/200 (65%), vs. 120/187 (65%), vs. 35/54(65%) per group respectively, p = NS. Depression was present in 109/200 (55%), vs. 100/187 (54%), vs. 29/54 (54%), respectively per group, p = NS. Psycho-spiritual distress was present in 65/200 (33%), vs. 44/187 (24%), vs. 11/54 (20%) per group respectively, P = NS. Logistic regression showed gender female correlated with higher psycho-spiritual distress (OR:2.08, p = 0.012), fatigue OR:1.32, p = 0.01, Well-Being OR:1.32, p = 0.02, Financial Distress OR:1.63, p = 0.00, age group &lt; 65, OR:9.24, p = 0.03. Conclusions: High prevalence of Anxiety, Depression and Spiritual Pain in O-OOAdCa. Less frequency of Spiritual Pain in the Oldest-Old when compared with the rest of the population. Highlights the importance of an integrative Psycho-spiritual care to this population. More research is needed.