tbuckley/cabot-search huggingface dataset:
IGF-Child-Pugh score as a predictor of treatment outcome in advanced hepatocellular carcinoma patients treated with sorafenib.
Authors: Yehia I. Abugabal, Manal Hassan, Roberto Pestana, Lianchun Xiao, Lauren Girard, Kanwal Pratap Singh Raghav, Jeffrey Morris, Reham Abdel-Wahab, Robert A. Wolff, James C. Yao, Hesham M. Amin, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2019)

4076 Background: Our recent published studies concluded that Lower levels of Insulin like growth factors-I (IGF-I) is correlated with shorter overall survival (OS) in HCC, and IGF-CP scores assigned based on serum bilirubin, serum albumin level, prothrombin time, and plasma IGF-1 provides better prognostic stratification. Sorafenib is the first frontline drug approved for the treatment of CP class A patients with advanced HCC. CP class A is the standard criterion for active therapy and trials entry in HCC. In this study we aimed at evaluating the predictive ability of IGF-CP to sub-stratify old CP classes and better predict sorafenib outcomes. Methods: Total of101 patients were prospectively enrolled from MD Anderson Cancer Center (MDACC). Blood sample were collected and tested for IGF-I and IGF-CP was calculated into class A, B and C. Median OS and progression free survival (PFS) were analyzed, and log rank test was used to compare PFS and OS between subgroups of IGF-CTP score of patients. Results: Among CP class, patients who were reclassified as IGF-CP (B) (Old A/new B) had significantly shorter OS in months (m) was 7.6m (95% CI= 5.23-26.51m ) and PFS of 2.99m (95% CI=2.53-5.26m) with (P&lt;0.001) in both, as compared to patients’ who classified as class A by both scoring systems (AA), who had OS of 15.43m (95% CI=12.3-31.18m) and PFS of 4.97m (95% CI=3.26-7.2m), (P&lt;0.001) in both. Conclusions: IGF-CTP score sub-stratified CP A class, and provided better prognostic stratification and accuracy than CP score in predicting sorafenib survival outcomes in HCC. This approach may lead to a paradigm shift in predicting efficacy and toxicity of systemic HCC therapies and in stratifying patients for active therapy and selection in HCC clinical trials.
Treatment modalities and oncological outcomes in a cohort of patients with advanced gastric cancer in Mexico.
Authors: Ana Karen Valenzuela, Mónica Isabel Meneses Medina, Vanessa Rosas Camargo, Haydee Cristina Verduzco-Aguirre, Jorge Humberto Hernandez-Felix, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2019)

e15590 Background: Gastric cancer (GC) represents the third leading cause of cancer related death in Mexico. Treatment modalities and outcomes have been infrequently reported in our population. Methods: we retrospectively reviewed medical records from all consecutive patients with histologically confirmed metastatic GC treated from January 2005 to December 2015 at our institution. EG junction primaries were excluded. Overall survival (OS) was estimated by Kaplan Meier method from histological diagnosis to dead or last date of follow up and compared by Log-rank test. P value &lt; 0.05 was considered significant. Results: 172 patients were included: 53.5% women, median age 55 years. Lauren’s classification: diffuse 57%, intestinal 20%, 3% mixed and 20% non-specified. Signet ring cells were found in 66% of cases. 37% have T4 tumors. Treatment modalities: 22% none treatment, 12% palliative care, 48% systemic chemotherapy at any time of disease course, 29% initial palliative surgery (derivative o gastrectomy), gastrectomy at any time in 14% (n 24). An R0 resection was achieved in 6/24 of patients. For those patients who received systemic chemotherapy (n 83) objective response rate was 34% and disease control rate 70%. Median OS according to treatment is shown in table. Only 35% of patients received second line chemotherapy and 7% a third line. Conclusions: patients with advanced GC have a dismal prognosis in our center. A third of patients present with terminal disease and are ineligible for oncological treatment. Chemotherapy can be offered to less than a half of patients. Palliative gastrectomy is offered to 12%. Multimodal therapy is associated with the best survival but could be offered to less than 10% of patients. [Table: see text]
The prognostic role of soluble transforming growth factor-β related with soluble programmed death-ligand 1 in biliary tract cancer.
Authors: Jin Won Kim, Hyerim Ha, Kyung-Hun Lee, Ah-Rong Nam, Ju-Hee Bang, Mei Hua Jin, Kyoung Seok Oh, Yung-Jue Bang, Do-Youn Oh
Journal: Journal of Clinical Oncology (2019)

4094 Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p &lt; 0.001; change after chemotherapy, Pearson correlation = 0.542, p &lt; 0.001). Patients with higher pre-chemotherapy sPD-L1 ( &gt; 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p &lt; 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p &lt; 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p &lt; 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ &gt; 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis.
Cancer cachexia, sarcopenia and hand-GRIP strength (HGS) in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): A prospective, observational study.
Authors: Sofia Agelaki, Konstantinos Rounis, Chara Papadaki, Alexia A Monastirioti, Lampros Vamvakas, Ioannis Gioulbasanis, Dimitrios Mavroudis, Dimitris A Makrakis
Journal: Journal of Clinical Oncology (2019)

9099 Background: Cancer cachexia syndrome, affecting up to 80% of patients (pts) with NSCLC, is characterized by systemic inflammation, negative protein and energy balance and poor patient outcome. HGS has been independently correlated with outcome in pts with advanced cancer. We investigated the potential association between cachexia, sarcopenia and HGS with outcome in pts with advanced NSCLC treated with ICIs. Methods: Fifty-five pts with NSCLC treated with ICIs were included in the analysis. Patient and disease characteristics and data on outcome measures were prospectively collected. Cancer cachexia was defined as weight loss &gt; 5% in the last 6 months, BMI &lt; 20% (or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia) and any degree of weight loss &gt; 2%. Baseline HGS was measured using the JAMAR analogue dynamometer. Results: Median age was 69 years, 50% of pts had non-squamous histology, 69% had PS 0-1, 61% had cancer cachexia and mean HGS was 27 kgs. Partial response, stable disease and progressive disease was recorded in 16%, 33% and 51% of pts, respectively. Median PFS was 4 months and median OS was 7.8 months. There was no association of cachexia or HGS with tumor burden, number of metastatic sites, LDH or neutrophil/lymphocyte ratio. Cachexia had a negative impact on HGS (p = 0,001). Pts with cachexia had lower response rates (4% vs 37%, p = 0.002), disease stabilization rates (32% vs 81%, p = 0.003) and shorter PFS (3.7 vs 8.2 months, p = 0.008) compared to non-cachectic pts. In multivariate analysis, cachexia independently predicted for shorter PFS (HR = 2.7, CI: 1.15 – 6.46, p = 0.023). Data on sarcopenia are being analyzed and will be presented at the meeting. Conclusions: Cancer cachexia is associated with lower response rates and disease stabilization rates and independently predicts for shorter PFS in pts with NSCLC treated with ICIs. To our knowledge this is the first report demonstrating a between the host’s immune and metabolic responses. The study of cancer cachexia may offer a new platform for the development of novel biomarkers of resistance to ICIs.
Reirradiation and/or surgery for locoregionally recurrent rectal cancer: A systemic review and meta-analyses.
Authors: Chai Hong Rim, Jeongshim Lee
Journal: Journal of Clinical Oncology (2019)

e15159 Background: Locoregional recurrence of rectal cancer (LRRC) might be occurred even after combination treatments including surgery and pelvic radiotherapy. Re-irradiation might provide the control of recurrence and/or symptomatic palliation, but possible complications are fearful hindrances. This study is to integrate information from various clinical studies, regarding re-irradiation and/or surgery of LRRC, and to provide practical information for clinical decision making. Methods: We searched four databases including pubmed, MEDLINE, Cochrane library, and Embase. The primary endpoint was overall survival (OS), and secondary endpoints were complications of grade ≥3, local control rate (LC), and symptomatic palliation rate. Results: A total of 17 studies, involving 18 cohorts and 744 patients with LRRC were included. Median OS among included studies ranged from 10 to 45 months (median: 24.5 months). Pooled 1-, 2-, and 3- year OS rates for all LRRC patients were 76.1% [95% confidence interval (CI): 61.7-86.3], 49.1% (38.5-59.7), and 38.3% (30.2-47.2), respectively. For patients who underwent re-irradiation and surgery (OP group), pooled 1-, 2-, and 3- year OS rates were 85.9% (95% CI: 74.0-92.9), 71.8% (54.6-84.4), and 51.7% (39.4-63.8). For patients who underwent re-irradiation but not surgery (non-OP group), pooled 1-, 2-, and 3-year OS rates were 63.5% (95% CI: 51.1-74.4), 34.2% (20.4-51.2), and 23.8% (15.4-34.8). The difference between two subgroups were significant for all 3 years analyses. Pooled 1-, 2-, and 3- year LC rates for OP group were 84.4% (95% CI: 75.5-90.4), 63.8% (55.2-71.5), and 46.9% (39.6-54.4), and for non-OP group were 72.0% (95% CI: 48.8-87.4), 54.8% (28.6-78.5), and 44.6% (16.6-76.5). The difference between subgroups were not statistically significant for all 3 years analyses. Pooled overall grade ≥3 acute complication rate was 11.7% (95% CI: 6.7-19.5), and for late complication was 25.5% (95% CI: 16.7-40.0). Patients who underwent surgery had a higher risk of grade ≥3 late complications (OR: 6.39, 95% CI: 3.2-12.7). Pooled symptomatic palliation rate was 75.2% (95% CI: 67.3-81.8). Conclusions: Re-irradiation and/or surgery might be an option with oncologic and palliative efficacies, where combined surgery provided more favorable survival outcome. However, late complication should be carefully considered especially when combined with surgery.
Case 52-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Gino V. Segre, G. Richard Dickersin
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 62-year-old man was referred to the hospital because of bone pain and hypophosphatemia.He was well until 10 years earlier, when a diagnosis of primary hypothyroidism was made and levothyroxine was begun. Five years before admission he experienced pain about the right hip; x-ray films of the pelvis showed no abnormality. One year before admission pain developed in the right groin and spread to the right buttock. Three months before admission he began to experience severe pain in the top of the left foot, the left ribs in the axillary area, and the right forearm. The . . .
Pan-tumor prognostic value of multiple immune protein expressions.
Authors: Tiphaine Lambert, Loic Verlingue, Léo Colmet-Daage, Brice Rauby, Nicolas Sanchez-Escobar Aladro, Marie Kerisit, Stephane Champiat, Muriel Wartelle, Francois Lion, Benjamin Besse, Eric Angevin, Antoine Hollebecque, Jean-Charles Soria, Jean-Yves Scoazec, Christophe Massard
Journal: Journal of Clinical Oncology (2019)

2618 Background: Using multiple immune-checkpoint proteins (ICP) screening in clinical routine could improve the evaluation of patients’ prognosis and ultimately tailor their treatment choice. We have evaluated this hypothesis in the context of early drug clinical trials. Methods: Patients included in MOSCATO-02 trial had refractory cancers and were candidate for phase 1 study. They were proposed to have a biopsy on an accessible tumor site for the analysis of four proteins by immunohistochemistry (IHC) and RNAseq: PD-L1, CD3, CD8 and FOXP3. Quantification of IHC staining was separated between intratumoral, intersitial and stromal by semi-quantitative method. Their relations to prognosis have been evaluated by survival Random Forest and compared to classical prognosis clinical variables, such as age and RMH score (calculated by the number of metastatic sites, lactate dehydrogenase (LDH) and serum albumin). Results: From April 2016 to September 2017, 228 patients included in MOSCATO-02 had a successful biopsy procedure with available IHC expression analysis. The main tumor subtypes were gastro-intestinal, urological, head and neck, breast and lung. RNAseq analyzes were performed for two thirds of the patients (N=170). Median overall survival was 8.1 months (CI95% 7.79 – 10, 65). We found that, in a cohort of phase I patients, RMH score was the most important variable used to estimate prognosis. Prognosis value of immune proteins were considerably inferior compared to clinical criteria. Among those proteins, the percentage of PD-L1 low score (1+) and average staining intensity of CD3 were the most valuables for prognosis evaluation. Variables with very few importance to prognosis estimation were CD8 and FOXP3 IHC scores, biopsy site and cancer types, subsequent treatments by immunotherapies or targeted therapies. Conclusions: In this cohort of patients with refractory cancers, the RMH score is confirmed as highly prognosis. Immune proteins could be used as a support to guide patient’s selection but does not constitute effective prognosis criteria.
<i>BRAF-V600E</i> and microsatellite instability prediction through CA-19-9/CEA ratio in patients with colorectal cancer.
Authors: Pashtoon Murtaza Kasi, Saivaishnavi Kamatham, Dorin Colibaseanu, Faisal Shahjehan, Amit Merchea
Journal: Journal of Clinical Oncology (2019)

e15065 Background: Colorectal cancer (CRC) is a heterogeneous disease. Specifically for patients with BRAF-V600E mutations and/or mismatch repair deficiency or microsatellite instability-high (dMMR/MSI-High), there have been significant advances in terms of treatment options. Early identification of these subsets of patients has both prognostic and predictive value. We wanted to highlight an observation of utilizing 2 simple, rapid and universally available lab tests i.e. carbohydrate cancer antigen 19-9 and carcinoembryonic antigen tumor markers, the ratio (CA-19-9/CEA) of which can distinctly identify these patients. Methods: We included and analyzed the ratio of CA-19-9/CEA levels in patients with metastatic CRC at Mayo Clinic from December 2016 to February 2019, where both the results were available. Non-parametric tests were done to compare and contrast the differences in the median ratio and tumor marker levels. Results: BRAF-V600E mutant CRC patients had a discordantly profound elevation in CA-19-9 levels as opposed to the CEA levels. The median CA-19-9/CEA ratio was 20 (range: 0.3-167.3) in BRAF-V600E MSS patients as opposed to 4.40 (range: 0.003-216.2) in all other patients, p-value of 0.007 (Table). Similarly, the mean CA-19-9/CEA ratio for BRAF V600E MSS tumors was 57.15 (S.D.± 62.76) versus 10.5 (S.D.± 33.90) for all other types. Furthermore, this discordant elevation is not seen in BRAF-mutant MSI-High or any MSI-High patients (median CA-19-9/CEA ratio - 0.46). Conclusions: To date, this is the first report utilizing the ratio of tumor markers CA-19-9/CEA as predictive rather than just prognostic markers. It clearly identifies BRAF-V600E MSS and the MSI-High CRC patients from other subsets.[Table: see text]
Effects of nivolumab alone or combination with molecular targeting agents for recurrent and refractory endometrial cancers with biomarker analyses.
Authors: Masashi Takano, Tomoyuki Yoshikawa, Hiroko Kouta, Miyuki Horikoshi, Takayoshi Asakawa, Kazuya Kudoh, Tsunekazu Kita, Morikazu Miyamoto, Tadashi Aoyama, Hiroko Matsuura, Hiroki Ishibashi, Hideki Iwahashi, Souichirou Kakimoto, Sayaka Ikeda, Kazuki Takasaki, Jin Suminokura, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2019)

e17124 Background: The immunotherapy drug, nivolumab, is now approved for several metastatic cancers, and has resulted in responses previously not seen with these cancers. Molecular targeting agents, such as mammalian target of rapamycin (mTOR) inhibitor, have also recently been shown to have modest activity for endometrial cancers, however, the efficacy was limited. The present retrospective analysis is to evaluate the efficacy of Nivolumab alone or combination with molecular targeting agents for recurrent and refractory endometrial cancers. Methods: A retrospective evaluation for medical charts of the patients were conducted: (a) the cases with histologically confirmed endometrial cancers, (b) those that had recurrent diseases, (c) diagnosed as refractory for the previous chemotherapy, (d) those that were treated with combination therapy using tri-weekly Nivolumab (100mg/body, every 3 weeks) alone, or combination with molecular targeting agents. The association with serum markers and response was also investigated. Results: A total of 16 patients were identified: 5 cases with endometrioid G1/2, 4 cases with endometrioid G3, and the 6 cases with serous, and one case with mucinous histology. Median age was 61 years old (range:43-76), and median number of the previous chemotherapy was 4 regimens (range:1-5). Combined drugs included everolimus (n = 9), temozolomide (n = 1), trametinib (n = 1), and nintedanib (n = 1). Among 12 cases with evaluable disease, a complete response over 20 months was observed in one case: a case with endometrial carcinoma G2 treated with Nivolumab and evelorimus (5mg/day, continuously). Stable disease more than three months was achieved in 8 cases (67%), and clinical benefit rate (CR+SD &gt; 3months) was achieved in 75% of the cases. Median progression-free survival was 5 months (range: 3-20+). Non-hematological adverse events included general fatigue, mucositis, dysgeusia, skin rash, edema, and liver dysfunction, but the toxicity greater than grade2 was observed and in a case with liver dysfunction (G3). There was no significant relationship between response and serum levels of VEGF, p53, and IL-6, however, clinical benefit was observed in higher abundance of endometrioid histology compared with serous subtype (86% vs. 50%). Conclusions: Combination therapy using Nivolumab with evelolimus could be a candidate for recurrent and refractory endometrial cancers. Biomarker analyses for the responders are mandatory for further investigation for larger clinical studies.
Association of a single nucleotide polymorphism in the ubxn6 gene with long-term non-progression phenotype in HIV-positive individuals
Authors: F. Díez-Fuertes, H.E. De La Torre-Tarazona, E. Calonge, M. Pernas, M. Bermejo, J. García-Pérez, A. Álvarez, L. Capa, F. García-García, M. Saumoy, M. Riera, A. Boland-Auge, C. López-Galíndez, M. Lathrop, J. Dopazo, A. Sakuntabhai, J. Alcamí
Journal: Clinical Microbiology and Infection (2019)
Impact of facility patient volume on overall survival in patients with muscle invasive bladder cancer undergoing trimodality bladder preservation therapy.
Authors: Benjamin Walker Fischer-Valuck, Soumon Rudra, Prashant Gabani, Ryan Mueller, Hiram Alberto Gay, Jeff M. Michalski, Christopher Abraham, Brian Christopher Baumann
Journal: Journal of Clinical Oncology (2019)

e16039 Background: There is an association between higher hospital and urologist case volume and improved survival outcomes for patients with bladder cancer. Limited data on facility volume and outcomes exists following trimodality bladder preservation with TURBT followed definitive chemoradiation (CRT). Methods: The National Cancer Database was queried for patients from 2004-2013 with urothelial bladder cancer (cT2-4aN0M0) receiving definitive CRT after TURBT. High-volume bladder preservation case volume (BPCV) was defined as facilities in the &gt; 70 th percentile of trimodality bladder preservation cases per ten years examined. We compared OS between high- and low-BPCV using Cox proportional hazard models. CRT was defined as &gt; = 5040cGy pelvic RT with chemotherapy given within 21 days. Propensity matching was performed to match high- and low-volume centers. Results: A total of 666 treatment facilities treating 1,635 patients with bladder preservation were identified with a median follow-up of 26 months (range 2-136 months). A 70 th percentile cutoff identified 497 patients that received treatment at 64 high-volume facilities. Median OS of patients treated at high BPCV centers was 37.0 months (95% CI, 27.9-33.6) versus 32.3 months (95% CI, 27.3-46.7) for patients treated at low BPCV centers (P = 0.004). High BPCV facilities were independently associated with a decreased hazard of death (HR, 0.86, 95% CI, 0.75-0.98; P = 0.031). When BPCV was analyzed as a continuous variable, an increasing number of bladder preservation cases per institute was also independently associated with improved OS (HR: 0.98, 95% CI, 0.97-0.99; P = 0.044). In the propensity score matched cohort, median OS of patients treated at high BPCV was 36.1 months (95% CI, 26.5-45.8) versus 28.1 months (95% CI, 23.9-32.3) for patients treated at a low BPCV facility (P = 0.016). Conclusions: In this observational cohort, treatment at a high BPCV facility was associated with improved OS. Causal factors for this finding may include greater institutional expertise in multidisciplinary bladder cancer care and potential advantages in treatment technology.