tbuckley/cabot-search huggingface dataset:
Inpatient burden of cervical and uterine cancer in the United States.
Authors: Shelby Corman, Chizoba Nwankwo, Nehemiah Kebede, Ruchit Shah
Journal: Journal of Clinical Oncology (2019)

e17009 Background: Limited data on the inpatient burden of cervical and uterine cancer exist. Therefore, this study assessed inpatient mortality, length of stay (LOS), and costs among hospitalized cervical and uterine cancer patients. Methods: This was a retrospective analysis of the 2006–2015 Healthcare Cost and Utilization Project – Nationwide Inpatient Sample (HCUP-NIS). Cervical and uterine cancer cases were identified using ICD-9 codes of 180.9 and 182.0 respectively. Patient demographics, hospital characteristics, and hospital outcomes (hospitalization rates, inpatient mortality, LOS, and costs) were examined. Multivariate logistic regression models were used to determine predictors of inpatient mortality. Generalized linear models were used to determine predictors of LOS and costs. Results: The analytic cohort included 67,429 cervical cancer and 74,394 uterine cancer cases resulting in 55.92 (±1.51) and 61.69 (±1.78) annual hospitalizations (per 100,000 women), respectively. The highest proportion of hospitalizations related to cervical and uterine cancer were among patients aged 45-65 years (38.9%, 45.7%), Caucasians (70.3%, 78.1%), having public insurance (59.6%, 67.4%), and admitted at large (63.3%, 63.1%), urban teaching (54.8%, 56.5%) hospitals. The mean LOS, proportion of patients who died during hospitalization, and hospital charges per stay were 4.22 (±0.02) days, 1.02%, and $9,646 (±$63.06) for cervical cancer and 4.39 (±0.02) days, 1.43%, and $10,790 (±65.47) for uterine cancer related hospitalizations. Age &gt; 65 years (vs 18-45 years) (OR: 3.656; 95% CI: 2.99 – 4.47), and higher Elixhauser mortality score (OR: 1.097; 95% CI: 1.09 – 1.10) were associated with higher inpatient mortality among cervical cancer patients. Predictors of inpatient mortality for uterine cancer were similar. Patient age, insurance, race, hospital size, urban (vs rural) location, region of the country, and Elixhauser mortality score emerged as significant predictors of LOS and cost per hospital discharge across both cancers. Conclusions: Cervical and uterine cancer are associated with considerable inpatient burden. There was considerable variation in inpatient mortality, LOS, and costs based on patient, hospital, and discharge level characteristics.
Artificial Intelligence (AI) and machine learning (ML) in risk prediction of hospital acquired pressure injuries (HAPIs) among oncology inpatients.
Authors: Vinod Ravi, Jing Zheng, Aparna Subramaniam, Lavonia G Thomas, John Showalter, John Frownfelter, Kelly Miller
Journal: Journal of Clinical Oncology (2019)

e18095 Background: Utilizing AI and ML is an emerging method to improve risk identification, characterization and stratification for clinical outcomes such as HAPIs. The Jvion Cognitive Clinical Success Machine (CCSM) utilizes the Eigen Sphere technique to factor in clinical, socioeconomic, and behavioral covariates at the individual patient level to maximize accuracy of risk prediction and provide insights on prevention of HAPIs. Methods: A retrospective analysis was performed utilizing claims and EHR data on 63,476 inpatient admissions between June 2016 and June 2018 at M D Anderson Cancer Center, a 660-bed oncology facility (Table). All risk assessment indicators in the data were removed prior to analysis by the CCSM to compute unbiased risk probabilities for HAPIs. The performance of the CCSM risk prediction for all new stage 2 and above HAPIs ( &gt; = Stage 2 HAPIs) was compared with the Braden scale using AUC. Results: The Jvion CCSM had an AUC of 0.84 compared to the AUC of 0.72 for the Braden scale in the prediction of &gt; = Stage 2 HAPIs. Conclusions: The AUC value indicates that the Jvion CCSM has better predictive accuracy than the Braden scale. It also has better discrimination in risk identification. Thus, Jvion CCSM can be a valuable tool in risk screening for HAPIs which can lead to early preventative interventions. [Table: see text]
Comparing late mortality risks among childhood cancer survivors: A report from the Childhood Cancer Survivor Study and British Childhood Cancer Survivor Study.
Authors: Miranda Marie Fidler, Kevin C. Oeffinger, Yutaka Yasui, David L Winter, Wendy Leisenring, Leslie L. Robison, Raoul Reulen, Yan Chen, Gregory T. Armstrong, Mike Hawkins
Journal: Journal of Clinical Oncology (2019)

10017 Background: It is unclear whether late-effect risks are comparable across international settings. We compared late mortality risks in the Childhood Cancer Survivor Study (CCSS) and British Childhood Cancer Survivor Study (BCCSS). Methods: 46,474 5-year survivors of childhood cancer diagnosed from 1970-1999 and &lt; 15 years age were included: 28,248 from the CCSS and 18,226 from the BCCSS. Late mortality (death ≥5 years from diagnosis) was assessed by linking to national vital statistics records. Adjusted ratios of the standardized mortality ratio (RSMR) and cumulative mortality probabilities were used to compare risks between cohorts. Treatment exposures were not available for the BCCSS, precluding comparison. Results: The cumulative all-cause mortality at 10 years from diagnosis was significantly lower in the CCSS (4.8%;95%CI:4.6%-5.0%) compared to the BCCSS (6.9%;95%CI:6.5%-7.2%); this was due to a lower probability of death from recurrence/progression of the primary cancer (CCSS = 3.3% vs. BCCSS = 5.8%), with significant differences observed in survivors of leukemia (7.9% vs 4.0%), Hodgkin lymphoma (2.5% vs 1.3%), CNS tumors (6.4% vs 4.4%), and sarcoma (6.5% vs 4.0%). However, with increasing time from diagnosis, risks became more similar. The CCSS ultimately had a greater cumulative mortality at 40 years from diagnosis, attributable to a 2-fold higher mortality from subsequent neoplasms (SNs) (RSMR:2.0;95%CI:1.8-2.3), cardiac (RSMR:1.7;95%CI:1.4-2.3) and pulmonary (RSMR:1.9;95%CI:1.4-2.5) causes, and other health-related deaths (RSMR:2.4;95%CI:2.1-2.9). When assessed by follow-up interval, the differences between the CCSS and BCCSS increased significantly for deaths due to SNs, cardiac and pulmonary causes, and other health-related deaths as time increased. Among those diagnosed more recently, the gap in all-cause mortality widened, with CCSS survivors diagnosed 1990-1999 experiencing approximately half the excess (RSMR:0.5;95%CI:0.5-0.6) observed in the BCCSS; this widening was driven by declines in the RSMR for most non-recurrence/progression causes of death. Conclusions: Our findings suggest that North American survivors may have received more intensive regimens during this time period to achieve sustainable remission and cure. However, the cost of this approach was a higher risk of death from late-effects. Which approach confers a net survival advantage will depend critically on the magnitude of the excess risk of late-effect deaths as the cohorts age.
The effect of race on adherence to NCCN Guidelines for patients with biliary tract cancers (BTC) after surgery.
Authors: Asrar Alahmadi, Gino Cioffi, Aman Opneja, Nirav Patil, David Lawrence Bajor, Joel N. Saltzman, Jill Barnholtz-Sloan, Richard T. Lee
Journal: Journal of Clinical Oncology (2019)

e15686 Background: BTC has a limited prognosis even for localized cancers (15-30% 5-year survival) emphasizing the importance of multidisciplinary management. NCCN guidelines recommend adjuvant chemotherapy (CT) +/- radiotherapy (RT) for high risk disease. We analyzed adherence to NCCN guidelines among patients following surgery for BTC and the influence of race. Methods: Subjects were identified from the National Cancer Database (NCDB) for BTC patients who underwent surgery and found to have metastatic lymph nodes (LN+) or positive surgical margins (M+) from 2004 to 2015. We defined adherence to NCCN guidelines as receiving surgery+ CT +/- RT and non-adherence to the guidelines as surgery +/- RT. Descriptive studies and multivariate logistic regression analysis was performed. Results: A total of 3,792 patients were identified with approximately half being female (55.4%) and between the ages of 50-69 (52.8%). Most were White (76.3%) followed by Black (10.6%), Hispanic (8.5%), and Asian (5.3%). The BTC included extrahepatic cholangiocarcinoma (CCA) (48.6%), gallbladder cancer (43.5%), and intrahepatic CCA (7.9%). Most patients had an R0 resection (71.9%) but also had LN+ disease (88.0%). There were no significant differences between racial groups in disease presentation (histological grade, tumor stage) and surgical outcomes (LN+, M+, hospital readmission, and 90 day post-surgery mortality). Hispanic patients as compared to White patients were less likely to be insured (85.7% vs 96.3%, p &lt; 0.001) and less likely to be treated at an academic facility (42.1% vs 52.1%, p = 0.008). Overall 29.7% of patient did not adhere to NCCN guidelines with Hispanics having the highest proportion of non-adherence as compared to Whites, (36.1% vs 28.7%, p = 0.029). On multivariate analysis, Hispanic race (HR = 1.51, 95% CI: 1.15-1.99) remained significant for receiving treatment non-adherent to NCCN guidelines. Conclusions: This study indicates that Hispanics are significantly more likely to receive non-adherent care in comparison to White patients in accordance with NCCN guidelines. More research is needed to confirm and understand the observed disparities and guide targeted interventions.
Modulating the tumor microenvironment to enhance efficacy of PARP inhibitors.
Authors: Manal Mehibel, Jimmy Xu, Anh Diep, Kaushik Thakkar, Caiyun G Li, Yiren Xiao, Erinn Rankin, Amato Giaccia
Journal: Journal of Clinical Oncology (2019)

e14715 Background: PARP inhibitors (PARPi) have demonstrated activity in HR deficient tumors through synthetic lethality. However, their clinical efficacy has not been highly promising, with response rates ranging between 30-60% for Olaparib, Talazoparib and Veliparib (1). This highlights the necessity to understand the mechanisms of resistance and how these agents work in the context of the tumor microenvironment. In this study, we explore the effect of hypoxia on the efficacy of PARPi in a range of HR-deficient tumors. Hypoxia is known to downregulate genes of homologous recombination (2) but its role in HR deficiency in still unknown. Methods: HR deficient tumor cell lines were treated with PARPi under both aerobic and hypoxic conditions. DNA damage markers such as γH2AX, 53BP1 and RIF1 were detected by immunofluorescence. Tumor xenografts were grown to 100 mm 3 prior to treatment with vehicle, PARPi, hypoxia activated cytotoxin, or the combination and tumor volumes were measured. Co-localization of apoptosis and hypoxia was detected by IHC. Finally, hypoxic signature in breast PDX models was correlated with their sensitivity to PARPi. Results: We found that hypoxic cells are significantly more resistant to PARPi in cell culture models. Efficiency of inhibition of PARP activity by these agents was similar under both air and hypoxia. The DNA damage marker γH2AX increased in cells treated in air, but not under hypoxia. There was no loss of 53BP1 protein that regulate engagement of the c-NHEJ pathway, indicating that HR has not been restored in these cells (3). However, it’s binding partner RIF1 was lost in hypoxia upon treatment indicating deficient signaling downstream of 53BP1. RIF1 is known to inhibit 5’ resection and its loss leads to resistance to PARPi in BRCA-deficient cells (4). In vivo, combining PARPi with hypoxia activated prodrugs led to substantial tumor growth delay in three xenograft models. DNA damage and apoptosis in these tumors was only detected outside of hypoxic regions positive for pimonidazole. In the breast PDX models, there was a strong correlation between the level of hypoxia in these tumors and their sensitivity to Olaparib. Conclusions: The significant increase in anti-tumor effects with the combination of PARPi and hypoxia-targeting cytotoxins leads us to propose a new strategy for tumors which are not responsive to PARPi alone. 1. Brown JS et al. Br J cancer 2016, 114, 713-5 2. Chan N et al. Cancer Res 2010, 70,8045-54 3. Bunting SF et al. Cell 2010, 141, 243-54 4. Chapman JR et al. Mol Cell 2013, 49, 858-71.
S1206: A dose-finding study followed by a phase II randomized placebo-controlled trial of chemoradiotherapy (CRT) with or without veliparib in stage III non-small cell lung cancer (NSCLC).
Authors: Athanassios Argiris, Jieling Miao, Mihaela C. Cristea, Allen M. Chen, Jacob Sands, Roy H. Decker, Scott N. Gettinger, Megan Eileen Daly, Bryan A. Faller, Kathy S. Albain, Ronald H. Yanagihara, Linda L. Garland, Lauren Averett Byers, Ding Wang, Marianna Koczywas, Mary Weber Redman, Karen Kelly, David R. Gandara
Journal: Journal of Clinical Oncology (2019)

8523 Background: Veliparib (V), a PARP inhibitor, may potentiate the antitumor effect of CRT in NSCLC. Methods: Eligibility included newly diagnosed unresectable stage III NSCLC. Patients were randomized to receive concurrent CRT with weekly carboplatin (AUC 2) and paclitaxel (45 mg/m 2 ) with V at 120 mg or placebo (P) twice daily during CRT followed by 2 cycles (every 21 days) of consolidation carboplatin (AUC 6), paclitaxel (200 mg/m 2 ) with V at 80 mg or P (per randomized arm) orally on days 1-7 of each cycle. Progression-free survival (PFS) was the primary endpoint. The accrual goal was 132 patients. Results: The dose-finding study results were previously presented (ASCO 2016;A8537). V 120 mg twice daily was the recommended phase II dose. A total of 31 eligible and evaluable patients were enrolled in the phase II randomized trial: 17 on V and 13 on P (1 patient in the V arm withdrew prior to starting any treatment, thus was not evaluable). The study was closed to accrual early due to the positive results from the PACIFIC trial that changed standard practice. Median follow-up among alive patients was 16 months. During CRT, the following grade (G) 3-4 adverse events (AE) were seen with V vs P: any G3 AE (6 vs 6), any G4 AE (2 vs 3), G3 pneumonitis (0 vs 1), G3 esophagitis (1 vs 1), G3 oral mucositis (1 vs 0), G3 anorexia (1 vs 1), G3 hyponatremia (0 vs 3), G3 anemia (1 vs 0), G3 neutropenia (3 vs 1), G3 thrombocytopenia (1 vs 0), G4 hypoglycemia (0 vs 1). Also, 2 patients per arm had G4 lymphopenia. During consolidation (11 evaluable patients with V; 10 with P), G3 anemia (1 vs 0), G3 anorexia (1 vs 0), G3 weight loss (0 vs 1), G3 dehydration (1 vs 0), G3 dysphagia (2 vs 0), G3 fatigue (1 vs 0), G3 hypomagnesemia (0 vs 1), G3 nausea (1 vs 0), G4 hyperglycemia (0 vs 1), G3-4 neutropenia (3 vs 0), G3 thrombocytopenia (1 vs 0), G3-4 lymphopenia (2 vs 1); a G5 pneumonitis occurred in the P arm. Response rates were 56% (95% CI, 31-78%) and 69% (95% CI, 38-91%) on the V and P arms, respectively. PFS at 1 year was 47% (95% CI, 23% - 68%) with V and 46% (95% CI, 19% - 70%) with P. Overall survival (OS) at 1 year was 89% (95% CI, 61%-97%) with V and 54% (95% CI, 25%-76%) with P. Adding the 6 patients treated at 120 mg in the phase I part, 1-year with V was 91% (95% CI, 69%-98%). Conclusions: V in combination with CRT was tolerable with expected toxicities that relate to the backbone regimen. In the small number of randomized patients there was a suggestion of promising survival with V that may provide rationale for future trials of PARP inhibitors with CRT. Clinical trial information: NCT01386385.
Case 4-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, J. Michael Lazarus, Robert T. McCluskey
Journal: New England Journal of Medicine (1984)

Presentation of CaseA 58-year-old woman was admitted to the hospital because of renal failure.There was a history of hypertension for 17 years. An intravenous urographic examination, performed at the time of the diagnosis, showed no abnormality. Eleven years before admission an automated scan of blood-chemistry determinations, performed elsewhere, showed no abnormality except that the alkaline phosphatase was 2.7 U (normal, 0.6 to 2.5 U); the cholesterol was 232 mg per 100 ml (normal, 140 to 310 mg). Another intravenous urographic examination, performed at a second hospital, was again reported to be negative. Three and a half years before . . .
Thyrointegrin αvβ3 nano targeted delivery of chemotherapy into solid tumors and its microenvironment.
Authors: Dhruba J. Bharali, Thangirala Institute Sudha, Kavitha Godugu, Noureldien H.E Darwish, Paul Joseph Davis, Kazutoshi Institute Fujioka, Shaker A. Mousa
Journal: Journal of Clinical Oncology (2019)

e14661 Background: Cancer cells and rapidly dividing endothelial cells relevant to tumors primarily express the αvβ3 integrin. Conjugation of tetraiodothyroacetic acid (tetrac) as diamino-tetrac to a poly (lactic-co-glycolic acid) (PLGA) polymer for the formation of Nano DAT was used to target a specific cell surface receptor on the αvβ3 integrin. PLGA prohibits cell entry and the nano shell could be loaded with a generic cancer chemotherapeutic. Without a payload, Nano DAT has anticancer and anti-angiogenesis properties. Methods: Xenografts of human urinary bladder cancer (263JBV) cells, human breast cancer (SUM149PT) cells, and human pancreatic cancer (SUIT-2) cells were established. Tumor growth and tumor content of cisplatin (263JBV xenografts), doxorubicin (SUM149PT xenografts), or of paclitaxel (SUIT-2 xenografts) were compared in the following daily treatment animal arms of cohorts for 3 weeks: (1) controls, (2) void PLGA Nanoparticle (NPs), (3) chemotherapeutic agent (cisplatin 1 mg/kg, doxorubicin 1 mg/kg, or paclitaxel 0.3 mg/kg), (4) Nano DAT 0.3 mg/kg, and (5) chemotherapeutic agent encapsulated into PLGA NPs and into Nano DAT. Results: Tumors in animals treated with Nano DAT bearing a payload of cisplatin, paclitaxel, or doxorubicin were associated with decreased tumor weight by 50%-60% (P &lt; 0.01) with &gt; 90% loss of cancer cell viability. Mean chemotherapeutic agents content of tumors (ng/gm of tissue) was 5-fold that of tumors from animals treated with chemotherapy, alone, and 3-fold that of tumors exposed to chemotherapy encapsulated into PLGA NPs, measured with an established LC/MS/MS method. Animals receiving cisplatin, alone, developed neurotoxicity (inability to use the hind limbs) in comparison to an animal group treated with Nano DAT bearing a payload of cisplatin, and was confirmed histopathologically. Conclusions: The payload capacity of Nano DAT for cancer chemotherapeutic agents and tumor-specific delivery of cancer chemotherapeutic agents significantly increases bladder, breast and pancreatic cancer content of, respectively, cisplatin and paclitaxel.
Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy
Authors: Hani Jrade, Harinad B Maganti, Christopher Cafariello, Christopher J Porter, Julien Yockell-Lelièvre, Hannah L Battaion, Safwat T Khan, Joel P Howard, Theodore J Perkins, Mitchell Sabloff, Caryn Y Ito, William L. Stanford
Journal: Blood (2018)
Comprehensive genomic profiling reveals distinct patterns of driver mutations and chromosomal alterations in acral and mucosal melanomas.
Authors: Zhengyun Zou, Qiuxiang Ou, Yu Ren, Qing Lv, Lanqun Qin, Lianjun Zhao, Shu Su, Xue Wu, Hua Bao, Ao Wang, Dongqin Zhu, Xiaonan Wang, Yang Shao, Baorui Liu
Journal: Journal of Clinical Oncology (2019)

9576 Background: The incidence of melanoma subtypes differs significantly among ethnicities. Ultraviolet (UV) radiation-driven melanomas are common in Caucasians, while non-cutaneous melanomas including acral and mucosal melanomas are more frequent in Asians. It will be of great interest and clinical relevance to decipher the molecular pathogenesis of different melanoma subtypes. Methods: We retrospectively studied a cohort of 89 Chinese melanoma patients who underwent surgical resection of their primary tumors followed by chemotherapy. Genomic profiling of primary melanomas was performed using next generation sequencing by targeting 422 cancer-relevant genes. The Kaplan-Meier method and logrank test were used for survival analysis, and a cox model was used for multivariate survival analysis. Results: Acral melanomas (54/89, 60%) were the most common subtype of this cohort, while cutaneous and mucosal subtypes accounted for 25% and 15%, respectively. Mutation profiling revealed that BRAF was most frequently mutated in cutaneous melanomas, but aberrant BRAF, RAS, KIT, and NF1 were almost evenly represented in acral and mucosal melanomas; of note, mucosal melanomas had a propensity for concurrent driver mutations. Chromosomal alterations were detected across all subtypes, and chr7p amplification significantly correlated with poor prognosis while independently of melanoma subtypes. Furthermore, acral and mucosal melanomas demonstrated higher rates of focal copy number variations (CNVs) than cutaneous melanomas. The amplification of CDK4/CCND1 and NOTCH2 was observed predominantly in acral melanomas , and RAD51 loss was significantly enriched in mucosal melanomas correlating with poor survival. In addition, the tumor mutation burden (TMB) was significantly lower in acral or mucosal melanomas than in cutaneous melanomas. Conclusions: Our findings revealed distinct patterns of driver mutations and chromosomal alterations in acral and mucosal melanomas in contrast to cutaneous melanoma, and highlighted the association of chromosome 7p amplification and RAD51 deletion with unfavourable survival in melanoma patients treated with standard chemotherapy.
Total cost of care for patients (pts) with stage II colon cancer (CC-II): A SEER-Medicare analysis.
Authors: Afsaneh Barzi, Xiayu Jiao, Joel W Hay, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2019)

6648 Background: Adjuvant chemotherapy (AC) for stage II colon cancer remains a controversial topic. We used Surveillance Epidemiology End Results (SEER) linkage with Medicare claims to explore the benefits of AC and cost of care in pts with CC-II diagnosed between 2004-2010. Methods: Colon cancer was identified using ICD-O-3 codes. TNM staging was used to classify pts as stage II. Cohort was restricted to pts who had surgery within 4months (mos) of the diagnosis and excluded pts who died within 3mos after the surgery as well as those who were enrolledon a health maintenance organization. We searched claims in the 4mos after surgery to identify pts who received AC using ICD-9 diagnosis and procedure codes, HCPCS, and revenue center codes. Kaplan-Meier method was used for survival analysis. Cost of care from payer’s perspective (Medicare) starting from surgery service to death or 3 years after surgery was captured from claims data. Results: A total of 16948 pts with CC-II diagnosed 2004-2010 were included in this analysis. Among those 14% received AC and 33% of them oxaliplatin. After adjusting for pts and tumor characteristics, probabilityof survival at 3years was 72.9% for pts who received AC and 74.2% for those who did not, HR=1.06 (95% CI, 0.96-1.17), with P-value: 0.229. The cost of care for the AC was significantly higher than the no-AC group (median $254,116 vs. $91,086). The biggest difference in between two groups was cost of outpatient and physician services. Costs for AC group was higher in years 1, 2, and 3 as seen in table. Conclusions: AC for CC-II is has a low value in elderly pts and should be avoided. [Table: see text]