tbuckley/cabot-search huggingface dataset:
Efficacy of carboplatin-based chemotherapy regimens in patients with bladder cancer in the neoadjuvant setting.
Authors: Hafiz Aslam, Sumera Bukhari, Muhammad Nadeem, Talha Awwal
Journal: Journal of Clinical Oncology (2020)

e17001 Background: There is paucity of evidence regarding efficacy of neoadjuvant chemotherapy regimens in bladder cancer patients. Radical cystectomy has been standard of care for patients with T2-T4, N0, M0 bladder cancer. However, recent trials have shown better survival rates in patients who underwent neo-adjuvant chemotherapy. Our meta-analysis is based on the data from non-randomized clinical trials on the efficacy of carboplatin based regimens. Methods: We conducted a systematic search of Medline (Pubmed) and Cochrane (from inception through May, 2018). Only published single arm clinical trials, abstracts of single arm clinical trials and data from one randomized trial on efficacy of neoadjuvant Carboplatin based therapies in patients with bladder cancer were included in our meta-analysis. Total of &gt; 70 studies were identified. Studies which were duplicate, included adjuvant therapy, systematic reviews or meta-analysis, trials not based on neoadjuvant therapy were excluded. A random effect model was used to calculate pooled proportions. Studies based on ITT protocol were analyzed separately as well as studies based on per protocol analysis. Comprehensive Meta-Analysis software version 3.0 was used. Results: The pooled proportion of pCR (pathologic complete response) calculated from trials based on ITT analysis was 0.23 (95% CI 0.19 to 0.28, P= 0.000). Tests for statistical heterogeneity was non-significant heterogeneity p-value = 0.79 (I2 = 0 %). The pooled proportion of pCR calculated from trials based on per-protocol analysis was 0.29 (95% CI 0.19 to 0.42, P= 0.002). Tests for statistical heterogeneity show nonsignificant heterogeneity p-value = 0.95 (I2 = 0 %). The pooled proportion of ORR (objective response rate) calculated from trials based on per-protocol analysis was 0.69 (95% CI 0.57 to 0.78, P= 0.001). Tests for statistical heterogeneity showed heterogeneity p-value = 0.203 (I2 = 37.3). The pooled proportion of cCR (clinical Complete response) calculated from trials based on per-protocol analysis was 0.25 (95% CI 0.18 to 0.34, P= 0.000). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.80 (I2 = 0%). The pooled proportion of cPR (clinical Partial Response) calculated from trials based on per-protocol analysis was 0.47 (95% CI 0.39 to 0.56, P= 0.59). Tests for statistical heterogeneity did not show heterogeneity p-value = 0.93 (I2 = 0%). Conclusions: Carboplatin based chemotherapy has shown significant efficacy in terms of over-all response rate, pathologic complete response and clinical complete response.
Impact of leucocyte modifications in patients with locally advanced cervical treated by chemoradiotherapy.
Authors: Christine Gennigens, Marjolein de Cuypere, Annelore Barbeaux, Frederic Forget, Johanne Hermesse, Elodie Gonne, Guy Heinrich Maria Jerusalem, Frederic Kridelka
Journal: Journal of Clinical Oncology (2020)

e18014 Background: Concomitant cisplatin-based chemoradiotherapy (CCRT), followed by image guided-adaptive brachytherapy (IGABT) is the recommended treatment for patients suffering from locally advanced cervical cancer (LACC). Methods: Between January 2010 and May 2017, 103 patients with LACC (FIGO 2009-stages IB2-IVA) received CCRT followed by IGABT. The objectives of this study were to evaluate the impact of white blood cells (WBC) and polymorphonuclear neutrophils (PMN) counts variations on outcomes. This variable was calculated by substraction between WBC or PMN levels at the first cycle (CB) and the last cycle (CL) of chemotherapy (CT)(DCB-CL). The data were reviewed retrospectively, with Cox regression for univariate and multivariate analysis. Results: The median age at diagnosis was 50 years. The median tumor size at diagnosis was 47mm. The majority of the patients had FIGO stage II (60.2%) or stage I (21.4%) disease with squamous histology (88.3%). Patients received a median dose of external-beam radiotherapy (EBRT) of 45 Gy (range 40-50.4 Gy) by 1.8-2 Gy fractions, with a median cumulative dose of all the radiotherapy of 85 Gy. The median duration of EBRT+IGABT was 51 days (range 31-94). All patients received at least one cycle of cisplatin, but the majority received 5 (40.4%) or 6 (39.4%) cycles. The median follow-up time for all patients was 30.1 months. The overall survival (OS) and recurrence-free survival (RFS) at 3 years was 81,4% and 76,8% respectively. Univariate analysis associated higher DCB-CL WBC and DCB-CL PMN with better OS and RFS. Multivariate analysis confirmed that DCB-CL WBC (HR, 0.856; 95% CI, 0.737-0.986; p = 0.018) and DCB-CL PMN (HR, 0.863; 95% CI, 0.750-0.994; p = 0.041) were associated with better OS and RFS respectively. A linear regression analysis was performed to cross the DCB-CL WBC/PMN and the number of CT cycles. This analysis reveals that an increasing number of CT cycles is linked to an increased DCB-CL WBC/PMN. Conclusions: Our study reveals the impact of DCB-CL WBC and PMN on outcomes. These two tests could become biomarkers during CCRT to discuss adjuvant treatments, but also to adapt our follow-up.
Phase I study results of APG-115, a MDM2-p53 antagonist in Chinese patients with advanced liposarcoma and other solid tumors.
Authors: Xing Zhang, Xizhi Wen, Guojuan Chen, Shan Zeng, Lichuang Men, Hengbang Wang, Shulan He, Yuxiang Ma, QiuZhong Pan, Yang Zhang, Ruiqing Peng, Desheng Weng, Wenqin Liu, Li Zhang, ZHIYAN LIANG, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2020)

11542 Background: APG-115 is a potent, small-molecule MDM2 inhibitor and immune modulator with promising antitumor activities in various tumors, especially those wild-type TP53 with MDM2 amplification ( TP53 wt +MDM2 amp). To better delineate safety, optimal dosage, and potential target population, we report updated results. Methods: Patients with advanced liposarcoma and other solid tumors received APG-115 (100-200 mg) orally every other day for 21 days of a 28-day cycle. The primary endpoints were safety and tolerability. Efficacy (assessed by RECIST v1.1), pharmacokinetics (PK) and pharmacodynamics (PD) have also been analyzed. Results: Enrollment of this Phase I study (CTR20170975) was completed. As of January 7, 2020, 21 patients (14 liposarcomas, 2 synovial sarcomas, 2 adenoid cystic carcinomas, 1 chondrosarcoma, 1 osteosarcoma, 1 rhabdomyosarcoma) were treated in 3 dose levels of APG-115: 100 mg (n = 11), 150 mg (n = 8) and 200 mg (n = 2). The median number of cycles of APG-115 was 2 (0; 6). Two DLTs were observed at 200 mg, thrombocytopenia and febrile neutropenia. The most common treatment-emergent adverse events (TEAEs) (≥20%) included leukopenia, thrombocytopenia, neutropenia, anemia, increased blood creatinine, hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia, vomiting, and nausea. The incidence of TEAEs was much lower at 100 mg. Serious AEs occurred in 5 patients (23.8%) which were assessed as possibly drug related by investigators. In 20 efficacy-evaluable patients, there was 1 patient with a partial response, 12 patients with stable disease, and 7 patients with progressive disease, yielding a disease control rate (CR, PR, SD) of 61.9%. Among the 13 patients (9 liposarcomas) who benefited, 11 had TP53 wt and 7 had TP53 wt +MDM2 amp, including one liposarcoma patient (150 mg) who had a PR, she was kept-up over 10 months, even though the treatment was discontinued for over 5 months, indicating the host immune modulatory effects of APG-115. Another patient with liposarcoma (100 mg, TP53 wt +MDM2 amp) had 28.5% tumor shrinkage at cycle 4 and remained on treatment. PK results showed an approximately dose-proportional increase in exposure on Day 1. PK-PD analyses showed the serum macrophage inhibitory cytokine-1 (MIC-1) increased with increased APG-115 exposure. Conclusions: The phase I data have demonstrated that APG-115 monotherapy was well tolerated, with minimal toxicity at 100mg (RP2D), and conferred encouraging anti-tumor activities in patients with liposarcomas. Clinical trial information: CTR20170975 .
Disparities in the treatment of brain metastases from breast cancer: Insights from the National Cancer Database.
Authors: Zena Chahine, Muhammad Salman Faisal, Thejus Thayyil Jayakrishnan, Stephen Abel, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

2037 Background: Breast cancer is the most common malignancy in women accounting for over 300,000 cases per year. Unfortunately, brain metastases are found in a sub-group of patients with breast cancer even at presentation. Management of brain metastases typically includes radiotherapy with conventional whole brain radiation therapy (WBRT) or more focused stereotactic radiosurgery (SRS). We queried the National Cancer Database (NCDB) to analyze the incidence of brain metastases at diagnosis in breast cancer patients, as well as trends in radiation use/technique. Methods: The NCDB was queried for patients who were diagnosed with breast cancer between 2004-2015 and had brain metastasis at presentation (N = 4,491). We excluded patients without brain radiation and inadequate follow up. Odds ratios were calculated to identify factors associated with treatment. Multivariable cox regression was used to determine predictors of survival. Results: Using the eligibility criteria above 1,505 patients were identified in the NCDB. The cohort had a median age of 58 years. A small portion were uninsured (7%) population uninsured and 81% of radiation treatments were delivered in metropolitan areas. Two hundred sixty-one (17.3%) patients received SRS while 1,244 (82.7%) received WBRT. Those patients with private insurance, higher income, metro location, and having care delivered at an academic center were more likely to receive SRS. Conversely, the likelihood of receiving WBRT was significantly higher in those with luminal type cancer, African Americans, the uninsured, and those located in urban areas or treated at a community cancer center. On Cox regression, predictors of worse survival were age &gt; 60 with Hazard Ratio (HR) 1.3 (95% CI 1.17-1.49), a comorbidity score &gt; 2 with HR 1.45 (95% CI 1.1-1.9), and extra cranial metastatic disease with HR 1.33 (95% CI 1.15-1.54). Conclusions: This analysis of the NCDB demonstrates socioeconomic and demographic disparities in the treatment of patients with brain metastases from breast cancer. There is a continued need to reduce these disparities and improve access to care for at-risk populations affected by this highly prevalent malignancy.
PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
Authors: Jiujie Cui, Jiayu Yao, Yu Wang, Yiyi Liang, Yongchao Wang, Feng Jiao, Xiao Zhang, Ting Han, Tiebo Mao, Qing Xia, Xiuying Xiao, Haiyan Yang, Li-Wei Wang
Journal: Journal of Clinical Oncology (2020)

TPS4665 Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P &lt; 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .
Neutrophil-lymphocyte score: A novel prognostic scoring system that utilized the dynamic change of neutrophil, lymphocyte, and albumin and its comparison to other indices.
Authors: Songzhu Zhao, Mingjia Li, Daniel Spakowicz, Sandip H. Patel, Andrew Johns, Madison Grogan, Abdul Miah, Marium Husain, Kai He, Erin Marie Bertino, Peter G. Shields, Lai Wei, David Paul Carbone, Gregory Alan Otterson, Carolyn J Presley, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2020)

3048 Background: Indications for immune checkpoint inhibitor (ICI) in cancer care are expanding rapidly. There is increasing need for accurate decision tool to better guide treatment. We have constructed a new prognostic scoring system, neutrophil-lymphocyte score (NRS), based on the nonlinear dynamic change of neutrophil to lymphocyte ratio (NLR) in relation to survival over the first cycle of ICI treatment. We compared this novel system to existing indices such as NLR, lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), Advanced Lung Cancer Inflammation Index (ALI), and Systemic Immune-inflammation Index (SII). Methods: This is a retrospective analysis of 837 patients at Ohio State University from 2011-18. Neutrophil (ANC), lymphocyte (ALC), platelet (plt), monocyte (AMC), albumin (alb), and body mass index (BMI) were collected at baseline. Repeat labs were collected at cycle 2. NLR = ANC/ALC, ALI = BMI x alb / NLR, LMR = ALC/AMC, SII = platelet x NLR, PLR = plt/ALC. NLR Ratio = baseline NLR / repeat NLR. Based on the association between NLR and the overall survival, we assigned 1 point (p) for baseline NLR &lt; 0.7, 6p for 0.7 to &lt; 2, 5p for 2 to &lt; 3, 4 p for 3 to &lt; 4, 3 for 4 to 5, 2p for 5 to &lt; 9, and 1p for ≥9. We also assigned 1p for NLR ratio &lt; 0.6, 2p for 0.6 to &lt; 0.8, 3p for 0.8 to &lt; 1.2, 5p for 1.25 to &lt; 1.4, 3p for 1.4 to &lt; 1.6, and 2p for ≥1.6. NLS = sum of these 2 scores . NLS_A = NLS*alb. Time-dependent receiver operator characteristic (ROC) curves with integrated time-dependent area under the curve (TD AUC) values were used to evaluate the predictive accuracy of each index for survival. Results: For baseline and repeat values, all indices were statistically significant (P &lt; 0.001) in predicting survival. Baseline integrated TD AUC were: ALI 0.704, NLR 0.692, SII 0.663, LMR 0.645, and PLR 0.612. All of the repeat indices at cycle 2 had higher prognostic value than their baseline counterparts. Integrated TD AUC for indices at cycle 2 were: ALI 0.740 (with baseline BMI), NLR 0.729, SII 0.694, LMR 0.671, and PLR 0.652. NLS_A was a composite score based on the dynamic change of NLR from cycle 1 to 2 and the treatment alb with integrated TD-AUC at 0.754. Conclusions: Indices constructed from ANC, ALC, AMC, Plt, alb, and BMI can be obtained inexpensively and provide great prognostic value for pts on ICI. We have constructed a novel scoring system (NLS_A) and demonstrated its improvement over the current prognostic indices. Studies with a larger cohort are needed to further improve and validate this system.
The role of baseline lesion selection on reader performance in oncologic clinical trials.
Authors: Anu Bansal, Ninad Mantri, Paul McCracken
Journal: Journal of Clinical Oncology (2020)

e14082 Background: Blinded independent central radiology review is integral to modern clinical trials in oncology. Based on previously published data based on overall adjudication rates, it is generally accepted that selection of a larger and more complete number of target and non-target lesions at baseline results in greater reader concordance and therefore improved data fidelity. Methods: A retrospective database review was performed across 27 trials spanning 15 clinical indications and 4 response criteria involving a total of 20,942 independent reads across numerous timepoints in 10,471 subjects by 119 readers. Adjudication rates and adjudication selection rates were calculated across and within all trials. Results: Readers selected a mean of 2.3 target lesions and 1.2 non-target lesions in each subject. The mean adjudication rate across all trials was 33%. However, adjudication selection rate should be a more accurate representation of reader performance. Within any one trial, 44% of readers who selected the greatest number of target and non-target lesions at baseline actually had adjudication selection rates below average. Conclusions: Readers who select more target and non-target lesions than their peers at baseline do not demonstrate significantly higher adjudication selection rates. This suggests that the number of lesions chosen at baseline may not be as strong a contributer to reader performance and data quality as previously surmised.
Incidence of colon cancer in younger population and lower incidence in Asians and females in central balley of California: Health disparity and epigenetic study model.
Authors: Soujanya Sodavarapu, Tyler McGrew, Mark Hobbins, Sami Haddad, Prakash Ramdass, Nashwan Obad, Amandeep Singh Gill, Dinesh Vyas
Journal: Journal of Clinical Oncology (2020)

e19028 Background: California acts as a boiling pot for immigration and the perfect ecosystem to study epigenetic changes from dietary and environmental factors in various ethnicities. It has a significant immigrant population, with approximately a quarter of the 40 million residents being foreign-born. The impact of migration on colon cancer incidences over time has not yet been characterized on a broad-scale level in the Northern Central Valley. This provides a unique opportunity to study the influence of migration, socio-economic gradient, environmental, and racial identity on the incidence of cancer in a subset of California’s San Joaquin County Population. Colon cancer affects around 100,000 annually, with white and African Americans being more often affected than Asians or Hispanics. Methods: This study is a retrospective, single-institution study that compared the socio-demographic variables and clinical characteristics of the patients who had a history of colon cancer in an academic central valley institution. We reviewed all the patient charts with a diagnosis of colon cancer from 2014-2019 and compared the age, demographics, socioeconomic status, comorbidities, pathology, treatment, and outcomes in the population. Appropriate statistics have been used for analyzing the data. Results: A retrospective chart review of all patients diagnosed with colon cancer from our Hospital from 2014-2019 which revealed that 23.9% of patients were younger than 50 years at diagnosis, and mean age of diagnosis is 56.6 years, compared to the national average where younger population constituted at 11% and mean age for men and women are 68 years and 72 years respectively. 36.5% were 50-60 years old, and 39.2% were &gt; 60 years old. Women constituted 31% in our group compared to compared to 35.6% nationally. Asians are 23% of the central California population, but only 11.4% of patients in our group of colon cancer patients were Asian/pacific islanders, with 6.4% being average weight. 36.7% of patients have obesity. 67.4% were &gt; 25 BMI, of which 12.8% were younger Hispanics with BMI 25-30. Adenocarcinoma is seen in 91.4% of patients. Conclusions: The younger population with male predominance is seen. Asians see a surge in colon cancer incidence, but the incidence rate is still lower. Epigenetic, western lifestyle, and environmental are responsible factors. Younger overweight Hispanics are increasing in number as well. We will present further subgroup analysis at presentation.
Clinical characteristics of chronic intestinal pseudo-obstruction: an analysis of 43 cases
Authors: Xiaoqing Li, Huijun Shu, Guijun Fei
Journal: BMJ (2017)

Objective
To analyze the clinical characteristics of chronic intestinal pseudo-obstruction (CIPO).


Methods
Clinical data of 43 patients with CIPO admitted in Peking Union Medical College Hospital from January 2012 to December 2016 were retrospectively reviewed. The clinical manifestations, laboratory examinations, images, treatment and prognosis of CIPO patients were analyzed.


Results
There were 14 males and 29 females with an mean age of (41.9±16.1)years. Among 43 patients, 32 were admitted in Gastroenterology Department, 6 in General Medicine Department and 5 in Rheumatology Department. Twenty two cases were primary CIPO and 21 cases were secondary. The main clinical manifestations were abdominal distension (93.0%), abdominal pain (67.4%), vomiting (67.4%), diarrhea (46.5%) and constipation (41.9%). All 43 patients had decreased body weight and body mass index (BMI); 23.3% (10/43) patients were complicated with anxiety and depression. 53.5% (23/43) patients presented anemia and 55.8% (24/43) patients presented hypoalbuminemia. All patients with CIPO underwent abdominal X-ray, which showed intestinal obstruction; but there was no evidence of mechanical obstruction. The average length of hospital stay was (28.4±13.9) d. Twenty three cases underwent gastric decompression; 28 cases (65.1%) received parenteral nutrition, and 21 cases (48.8%) received enteral nutrition; and 9 abdominal operations were performed in 8 patients.


Conclusion
When clinical symptoms of intestinal obstruction appear without mechanical cause, CIPO should be considered and secondary factors should be screened. Unnecessary surgery should be avoided in CIPO patients.


Key words: 
Intestinal pseudo-obstruction; Disease attributes; Chronic