tbuckley/cabot-search huggingface dataset:
Characteristics of cancer patients with a history of solid organ transplantation: Analysis of a patient cohort reporting to a large cancer center.
Authors: Susen Burock, Stefanie Nicklich, Leonie Hartmann, Claas Ulrich, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2019)

1558 Background: Solid organ transplant recipients have a 2-4-fold elevated risk of developing cancer compared to the general population due to immunosuppressive therapy. Cancer patients with a history of organ transplantation (TPx) may or may not have a cancer attributed to immunosuppression. Here we report on a cohort of cancer patients of the Charité, diagnosed with the first occurrence of a solid cancer in 2010-2014 and a history of TPx. Methods: The cancer registry database of the Charité Comprehensive Cancer Center was queried for patients diagnosed with the first occurrence of solid cancer between 2010 and 2014 and a previous solid organ transplantation. General tumor and patient characteristics as well as outcome were analyzed. Results: A total of 226 patients (151 male, 75 female) were identified and included in the analysis. Transplanted organs included kidney in 148 patients, liver in 63, and heart, lung or a combination of both in 15. The median age at transplantation and initial tumor diagnosis was 54.7 years and 63.4 years respectively. Median interval between organ transplantation and diagnosis of the cancer was 8.1 years, range 0 - 39 years. 60.6% of cancers developed &gt; 10 years after TPx. The interval between TPx and development of cancer inversely correlated to patient age at TPx, with a median of 17.9 years (age group 18-34), 13.0 years (35-49), 6.7 years, (50-64), and 5.3 years, (65+ years). The majority of cancers occurred within the first 10 years after TPx, however especially for the age group 35-49 cancer diagnoses peaked 20-25 years after transplantation. The most common cancer types where non-melanoma skin cancer (34%), followed by kidney (15%), lung (13%) prostate (8.61% of all male patients) and colorectal (4.87%). Median survival of all patients after tumor diagnosis was 4.6 years, with 1.0 years for lung cancer, 4.6 years for colorectal cancer, 5.7 years for prostate cancer respectively. The median OS was not yet reached for non-melanoma skin cancer and kidney cancer. Conclusions: Our data support the necessity of long- term follow up and cancer screening in patients after organ transplantation beyond the commonly practiced 10 years post transplantation screening.
Case 35-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Raymond J. Maciewicz, Raymond A. Sobel
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 25-year-old woman was admitted to the hospital because of headaches.She was well until three years earlier, when she began to experience occasional headaches that usually occurred in the bifrontal or occipital region and lasted for several days. Three weeks before admission headaches began to occur almost daily, were often present when she arose from bed, and were accompanied by nausea, vomiting, lethargy, forgetfulness, and confusion. Three days before entry a physician prescribed hydroxycodone, but the headaches worsened and she came to the hospital.The patient was married, with a son aged 2 1/2 years. Her . . .
Risk factors for renal failure (RF) during high-dose chemotherapy (HDCT) and outcomes for patients (pts) with relapsed germ-cell tumors (rGCT).
Authors: Kevin Juan Zhang, Nasser H. Hanna, Mohammad Issam Abu Zaid, Rafat Abonour, Costantine Albany, Lawrence H. Einhorn, Nabil Adra
Journal: Journal of Clinical Oncology (2019)

e16042 Background: Pts with rGCT can be cured with salvage chemotherapy (CT). We evaluated risk factors and outcomes of pts who developed RF during HDCT for rGCT. Methods: All pts were planned to receive 2 consecutive courses of HDCT per protocol (N Engl J Med 2007;357:340-8). Characteristics and outcomes of pts sustaining grade ≥3 RF were analyzed and compared with those not sustaining grade ≥3 RF. Results: 21 (4%) of 473 pts had grade ≥3 RF: median age 38 (range 25-70), median creatinine 1.2 (0.6-1.8), median creatinine clearance (CrCl) 94 (48-216), median body mass index 27.1 (19.9-34.2). Median # prior standard-dose cisplatin-based CT cycles 5 (4-8) and median total dose of cisplatin 1000mg (600-1976). 10/21 pts had history of renal disease prior to HDCT, 4 had hypertension, 2 had diabetes, 2 had solitary kidney and 5 had stent or nephrostomy tube for obstruction. 20/21 pts developed neutropenic fever. 5 required total parenteral nutrition and 18 required hemodialysis (HD) during HDCT. 6 of 21 died during HDCT. 10 of 15 pts who survived HDCT had renal function recover to baseline, 2 came off HD but renal function was not restored to baseline, and 3 continued to be on HD at most recent f/u. In comparison to pts (n = 452) who did not experience grade ≥3 RF, pts (n = 21) who did experience grade ≥3 RF were more likely treated with HDCT ≥ 3rd line setting (38% vs 15%), had ECOG PS 1/2 (53% vs 18%), less likely to receive both courses of HDCT (33% vs 94%), more likely to experience GI (62% vs 11%), hepatic (43% vs 3%), pulmonary (38% vs 2%), and infectious (95% vs 1%) grade ≥ 3 toxicities; treatment-related death was also higher in this group (29% vs 2%). With a median f/u of 10 months after HDCT, 5 pts had no evidence of disease (NED), 3 were alive with disease, 6 died of disease, 6 died from complications of HDCT, and 1 lost to follow up. Conclusions: Irreversible RF during HDCT for rGCT is uncommon, but is associated with higher rates of infectious, GI, hepatic, pulmonary complications and treatment-related death. These pts are more heavily pre-treated, have lower baseline PS, and are likely to have history of renal disease prior to HDCT. However, most surviving pts recovered their renal function and 5/21 remain alive with NED.
SP0199 CASE 2 DISCUSSANT: HOW TO TREAT DIFFICULT ILD
Authors: Toby Maher
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> ILD frequently results in progressive and irreversible destruction of the lung through scarring. Prompt therapy can help rescue lung function and prevent subsequent respiratory decline. This case will demonstrate the challenges inherent in diagnosing and managing interstitial lung disease in the context of connective tissue disease <h3>Objectives:</h3> To discuss typical presentation of CTD-ILD Review challenge of making diagnosis and choosing best treatment. Assess treatment options, duration of therapy and measurement of treatment response. <h3>Conclusion:</h3> A range of therapeutic options exist for CTD-ILD albeit with a paucity of trial data to support best practice. Accurate diagnosis of systemic disease, paired with careful assessment and monitoring of the respiratory system are vital in ensuring optimal management. Intravenous therapy is often necessary in advanced disease or for disease which proves refractory to oral immunosuppression. <h3>References:</h3> [1] Saunders P, Tsipouri V, Keir GJ, Ashby D, Flather MD, Parfrey H, Babalis D, Renzoni EA, Denton CP, Wells AU, Maher TM. Rituximab versus cyclophosphamide for the treatment of connective tissue disease-associated interstitial lung disease (RECITAL): study protocol for a randomised controlled trial. Trials2017; 18: 275. [2] Maher TM. Immunosuppression for connective tissue disease-related pulmonary disease. Seminars in respiratory and critical care medicine2014; 35: 265-273. <h3>Disclosure of Interests:</h3> Toby Maher Grant/research support from: Received funds from BI advisory board participation and conference travel. Received research funding and/or consulting fees or other remuneration from GSK, UCB, AstraZeneca, Roche, Bayer, Biogen Idec, Cipla, Prometic, and Sanumed. Toby Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&amp;D and UCB., Consultant for: Toby Maher has received consultancy or speakers fees from Apellis, AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Galapagos, GlaxoSmithKline R&amp;D, Indalo, Pliant, ProMetic, Roche, Samumed and UCB; and has received consultancy fees from Galecto.
Correlation of inflammation-related markers with MDSC and IL-17, and use as prognostic indicators in patients with advanced gastric and colorectal cancers.
Authors: Masahiko Shibata, Daisuke Ujiie, Mai Ashizawa, Tomohiro Kikuchi, Hirokazu Okayama, Shoutarou Fujita, Wataru Sakamoto, Takahiro Nakajima, Hisahito Endo, Motonobu Saito, Tomoyuki Momma, Tatsuo Shimura, Koji Kono, Seiichi Takenoshita
Journal: Journal of Clinical Oncology (2019)

e14204 Background: Although a causal relationship for inflammation and immunity of cancer is more widely accepted today, the precise cell mechanisms mediating this relationship have not been elucidated. Accumulating evidence suggests that myeloid-derived suppressor cells (MDSC), may contribute to the negative regulation of immune responses during cancer and inflammation. IL-17 is a pro-inflammatory cytokine that is primarily secreted by T helper (Th)17 cells and we have reported that IL-17 correlates with immunosuppressive conditions in patients with cancer. Methods: PBMC (peripheral blood mononuclear cells) were harvested from 106 patients including 43 with gastric and 63 with colorectal cancer. PBMC were stimulated with PHA (phytohemagglutinin) and the production of IL-17 was measured by ELISA. MDSC were detected by flow cytometry (CD11b + ,CD14 - ,CD33 + ). The levels of CRP (C-reacting protein) and NLR (neutrophil to lymphocyte ratio) were used as inflammatory markers. Results: Both of MDSC and IL-17 production were increased in patients with advanced stages, and correlated with each other, inflammatory markers and immune suppression. The patients were divided with average levels of MDSC and IL-17 production and the prognosis were analyzed with Kaplan-Meier method. The overall survival of patients with high MDSC or high IL-17 production were significantly worse than those with low MDSC or low IL-17 production, respectively, in patients with stages III and IV, although the differences were not significant in patients with stages I and II. Conclusions: Thus these inflammatory markers are closely related with systemic inflammation involving IL-17 and with immunosuppression driven by MDSC, and are effective prognostic indicators in patients with stages III and IV gastric and colorectal cancer.
Deferred cytoreductive nephrectomy among patients with newly diagnosed metastatic renal cell carcinoma treated initially with sunitinib.
Authors: Bimal Bhindi, Jeffrey Graham, Connor Wells, Frede Donskov, Felice Pasini, Jae-Lyun Lee, Naveen S. Basappa, Aaron Richard Hansen, Lori Wood, Christian K. Kollmannsberger, Ravindran Kanesvaran, Takeshi Yuasa, D. Scott Ernst, Sandy Srinivas, Brian I. Rini, I. Alex Bowman, Sumanta K. Pal, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2019)

4578 Background: While the CARMENA trial prompts more caution with upfront cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC), 17% of patients in the sunitinib alone arm underwent deferred CN (dCN). Upfront systemic therapy has been proposed as a potential litmus test to identify patients suitable for CN, but data on outcomes are limited. We sought to characterize outcomes of dCN after upfront sunitinib relative to sunitinib alone. Methods: Patients with newly diagnosed mRCC receiving upfront sunitinib were identified from the International mRCC Database Consortium (IMDC) from 2006-2018. All CNs done after initial sunitinib were included, excluding CNs performed after sunitinib failure. The outcomes were overall survival (OS) and time to treatment failure (TTF). Kaplan Meier and multivariable Cox regression analyses were performed; dCN was analyzed as a time-varying covariate to account for immortal time bias. Results: The cohort included 708 patients of whom 53 (7.5%) underwent dCN at a median of 6.5 months (IQR 3.5,10.5) from diagnosis. Patients in the dCN group were more likely to have better Karnofsky performance status (KPS), intermediate IMDC risk, fewer metastatic sites, and response to upfront sunitinib (Table). There were 604 deaths during a median follow-up of 63 months. Median OS and TTF with dCN were 43.5 and 19.8 months vs. 9.4 and 4.3 months without, respectively. Upon multivariable analysis, dCN remained significantly associated with OS (HR 0.45, 95%CI 0.31-0.65; p &lt; 0.001) but not TTF (HR 0.73, 95%CI 0.52-1.01; p = 0.056). Conclusions: Patients who received dCN were carefully selected and achieved long OS. With these benchmark outcomes, optimal selection criteria need to be identified and confirmation of the role of dCN in a clinical trial is warranted. [Table: see text]
A Phase I/II Trial of Cetuximab in Combination with Interleukin-12 Administered to Patients with Unresectable Primary or Recurrent Head and Neck Squamous Cell Carcinoma
Authors: Elizabeth L. McMichael, Brooke Benner, Lakhvir S. Atwal, Nicholas B. Courtney, Xiaokui Mo, Melanie E. Davis, Amanda R. Campbell, Megan C. Duggan, Kallan Williams, Kyle Martin, Kala Levine, Gonzalo N. Olaverria Salavaggione, Tiffany Noel, Akaansha Ganju, Sarvani Uppati, Bonnie Paul, Thomas Olencki, Theodoros N. Teknos, Panos Savvides, Susheela Tridandapani, John C. Byrd, Michael A. Caligiuri, Stephen V. Liu, William E. Carson
Journal: Clinical Cancer Research (2019)

Abstract Purpose: mAbs including cetuximab can induce antibody-dependent cellular cytotoxicity (ADCC) and cytokine production mediated via innate immune cells with the ability to recognize mAb-coated tumors. Preclinical modeling has shown that costimulation of natural killer (NK) cells via the Fc receptor and the IL12 receptor promotes NK-cell–mediated ADCC and production of cytokines. Patients and Methods: This phase I/II trial evaluated the combination of cetuximab with IL12 for the treatment of EGFR-expressing head and neck cancer. Treatment consisted of cetuximab 500 mg/m2 i.v. every 2 weeks with either 0.2 mcg/kg or 0.3 mcg/kg IL12 s.c. on days 2 and 5 of the 2-week cycle, beginning with cycle 2. Correlative studies from blood draws obtained prior to treatment and during therapy included measurement of ADCC, serum cytokine, and chemokine analysis, determination of NK cell FcγRIIIa polymorphisms, and an analysis of myeloid-derived suppressor cell (MDSC) frequency in peripheral blood. Results: The combination of cetuximab and IL12 was well tolerated. No clinical responses were observed, however, 48% of patients exhibited prolonged progression-free survival (PFS; average of 6.5 months). Compared with patients that did not exhibit clinical benefit, patients with PFS &amp;gt;100 days exhibited increased ADCC as therapy continued compared with baseline, greater production of IFNγ, IP-10, and TNFα at the beginning of cycle 8 compared with baseline values and had a predominance of monocytic MDSCs versus granulocytic MDSCs prior to therapy. Conclusions: Further investigation of IL12 as an immunomodulatory agent in combination with cetuximab in head and neck squamous cell carcinoma is warranted.
Practical exploration and research of Watson for oncology clinical decision support system in real-world and localized practice.
Authors: Zhonghe Yu, Zuochao Wang, Xuemei Ren, Defa Lou, Xia Li, Hongli Liu, Xiuliang Zhang
Journal: Journal of Clinical Oncology (2019)

e18304 Background: Watson for Oncology (WFO) is a cognitive computing system developed by the IBM and trained by Memorial Sloan Kettering Cancer Center to provide evidence-based treatment recommendation for cancer patients. This study is to explore the impact on clinical treatment decision and patient communication based on the standard workflow we established of applying WFO in real-world clinical practice. Methods: From May 2018 to January 2019, 57 patients with advanced malignant tumors, including lung, breast, colorectal, gastric, esophageal, liver, ovarian and endometrial cancer, treated at Oncology Department of Beijing Chaoyang Integrative Medicine Emergency Medical Center were included in the study, of which 28 males and 29 females aged 29-89 years old. Treatment plan of each patient generated by WFO was compared with NCCN guidelines and Chinese local CSCO guidelines, and then evaluated and determined by MDT for final decision. Proportion of WFO recommendation fully or partially followed by clinicians was analyzed. Moreover, survey by questionnaire was conducted to collect feedback from these patients on their satisfaction of treatment and communication process. Results: Of all 57 patients enrolled, WFO’s options were highly concordant with NCCN guidelines and CSCO guidelines, and the finally adopted treatment plans after deliberately evaluated and discussed by MDT were 100% in the WFO recommended or for consideration category. Patient satisfaction and the compliance with instruction was significantly improved compared with historical data. Localization was most required in gastric, liver and esophageal cancer due to local drugs and therapies not available in WFO. Conclusions: This study verified that the artificial intelligent clinical decision supporting system can be applied in Chinese clinical practice to achieve high patient satisfaction and good efficacy. WFO meets Chinese and international standards for treatment, which will promote the standardized development of cancer treatment in China. Optimization, iteration, upgrading and localization are required for better practicability of WFO.
KMT2C mutation associated with tumor mutational burden in small cell lung cancer.
Authors: Weiguang Gu, Hongbiao Wang, Kunsong Li, Ge Wei, Junkai Zhang, Shiyue Zhang, Lin Zhang, Xiaoliang Shi, Angen Liu
Journal: Journal of Clinical Oncology (2019)

e20098 Background: Immune checkpoint inhibitors are used to treat small cell lung cancer (SCLC). Tumor mutational burden (TMB) emerges as a promising predictor of immunotherapy efficacy, but the relationship between TMB and genetic features of SCLC remains unclear. In this study, we explored the correlation between genetic profiles and TMB in SCLC. Methods: FFPE tumor and matched blood samples were collected from 119 SCLC patients for panel targeted based next-generation sequencing. Genomic alterations (GAs) including single nucleotide variations, short and long insertions/deletions, copy number variations and gene rearrangements were assessed. Results: This study enrolled 114 SCLC and 5 mixed SCLC patients (91 males and 28 females) with a median age of 59 years. Median TMB was 9.3 muts/Mb (25% quantile: 6.3 muts/Mb, 75% quantile: 13.2 muts/Mb). For all patients, 31 (26%) had low TMB (≤6.3 muts/Mb), 55 (46%) had intermediate TMB (6.4-13.1 muts/Mb), and 33 (28%) had high TMB (≥13.2 muts/Mb). KMT2D mutations (mut), included substitution/indel (6/25) and truncation (19/25). KMT2D exhibited substitution/indel (6/25) and truncation (19/25) mutations in 19% of SCLC tumors while KMT2C exhibited substitution/indel (11/17), gene homozygous deletion (1/17) and truncation (5/17) mutations in 12% of SCLC tumors. Tumors with KMT family gene mut (KMT2C and KMT2D) (n = 33) had higher TMB (11.7 vs. 8.5 muts/Mb, p = 0.009). KMT2C mut tumors had higher TMB than KMT2C wildtype (wt) tumors (15.2 vs. 9.2 muts/Mb, p = 0.0036). TP53 mut occurred in 86% of KMT2C mut tumors and KMT2C/TP53 co-mutated tumors had higher TMB than KMT2C wt/TP53 mut tumors (17.8 vs. 9.3 muts/Mb, p = 0.0035) or KMT2C wt/TP53 wt tumors (17.8 vs. 5.4 muts/Mb, p = 0.027). Conclusions: Our data indicates that KMT family genes were frequently mutated in SCLC. KMT2C mut positively correlated with higher TMB and KMT2C co-mutated with TP53 or FAT1 may have a synergic effect on TMB. Our study explored a novel relationship between GAs and TMB that may greatly improve immunotherapeutic strategies for SCLC.
Are there any significant impacts of patient age and prior treatment profile with docetaxel on the efficacy of cabazitaxel in patient with castration-resistant prostate cancer?
Authors: Takeo Kosaka, Hiroshi Hongo, Ryuichi Mizuno, Nobuyuki Tanaka, Toshikazu Takaeda, Kazuhiro Matshumoto, Mototsugu Oya
Journal: Journal of Clinical Oncology (2019)

e16522 Background: The correlation of the oncological outcomes of patient age in metastatic castration resistant prostate cancer (mCRPC) patients have not been unclear. Materials and Methods: This study included a total of 56 consecutive Japanese mCRPC patients treated with cabazitaxel and assessed the prognostic significance of cabazitaxel at Keio University Hospital from 2014 to 2019 were included., focusing on patient age and the correlation of efficacy between docetaxel and cabazitaxel. All patients received cabazitaxel at 20-25 mg/m 2 administered intravenously on day 1 of each treatment cycle, together with prednisone 5 mg twice daily. Prophylactic administration of G-CSF was prescribed to all the patients. Results: The median overall survival (OS) periods after the introduction of cabazitaxel was 16.1 months. A 30% PSA response to cabazitaxel was achieved in 5 (50.0%) patients with ≧75 years (n = 10) and 19 (41.3%) patients with less than 75 years (n = 46). There was no significant correlation between the PSA response and patients’ age (p = 0.087). A 30% PSA response to cabazitaxel was achieved in 25 (43.9%) patients. A 30% PSA response to cabazitaxel was achieved in 15 (57.6%) and 10 (33.3%) patients with and without that to docetaxel, respectively. There was no significant correlation of the PSA response between docetaxel and cabazitaxel (p = 0.106). Univariate and multivariate analysis revealed that there were no significant correlation of patient age, the response to prior docetaxel therapyor cycles of docetaxel therapy with shorter OS. Conclusions: These results indicate that the introduction of cabazitaxel for mCRPC patients could result in oncological outcomes without any association with patient’s age and the profiles of previous docetaxel therapy.