tbuckley/cabot-search huggingface dataset:
Association of diagnosing physician and hospital characteristics with the use of radical cystectomy among patients with muscle-invasive bladder cancer.
Authors: Hemalkumar B Mehta, Vishnukamal Golla, Mohamed Danny Ray-Zack, Yong Shan, Yong-Fang Kuo, Karim Chamie, Stephen Bentley Williams
Journal: Journal of Clinical Oncology (2019)

6576 Background: Only one out of five muscle-invasive bladder cancer patients receive radical cystectomy, a guideline-recommended treatment. Prior studies evaluated patient characteristics associated with radical cystectomy use. We aimed to determine bladder cancer diagnosing physician and hospital characteristics associated with the use of radical cystectomy. Methods: This cohort study used linked SEER-Medicare Data from 2002 to 2011. We included older adults (age&gt;65 years) diagnosed with muscle-invasive bladder cancer. For each patient, a urologist who performed transurethral resection of bladder tumor was assigned as a diagnosing physician. The diagnosing physician was assigned to one hospital based on where he/she performed more than half of all urologic surgeries. Two-level hierarchical model (patients nested within hospitals) were constructed to determine the association of patient, physician and hospital characteristics with radical cystectomy use. Results: A total of 7,097 patients were diagnosed by 4601 physicians who were affiliated with 822 hospitals. Overall, the radical cystectomy utilization rate was 26.5%. Only 4.8% of the variation in radical cystectomy was attributed to the hospital level. In the two-level hierarchical model, patients diagnosed by female physicians were more likely to undergo radical cystectomy (32.8% vs. 25.8%; OR=1.63, 95% CI=1.31-2.02). Higher radical cystectomy volume by diagnosing physicians and hospitals increased the radical cystectomy use (Table). Diagnosing physician characteristics (age, years in practice, employment status), and hospital characteristics (teaching states, location, type of hospital) were not associated with radical cystectomy use. Patient characteristics such as age, male, higher comorbidity burden were associated with lower likelihood of radical cystectomy use. Conclusions: Physician and hospital factors do not largely contribute to the receipt of radical cystectomy. Radical cystectomy volume by diagnosing physicians and hospital drives radical cystectomy use.[Table: see text]
Anlotinib treatment in locally advanced or metastatic medullary thyroid carcinoma: A multicenter, randomized, double-blind, placebo-controlled phase IIB trial.
Authors: Dapeng Li, Ping Zhang Tang, Xiaohong Chen, Minghua Ge, Yuan Zhang, Zhuming Guo, Jun Wang, Feng Shi, Jiewu Zhang, Ying Cheng, Zhendong Li, Hui Liu, Jianwu Qin, Rui Huang, Ruochuan Cheng, Zhengang Xu, Yihebali Chi, Xiangqian Zheng, Ming Gao
Journal: Journal of Clinical Oncology (2019)

6019 Background: Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferative signaling. Our previous single-arm phase 2 ALTN/MTC trial (NCT01874873) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in locally advanced or metastatic medullary thyroid carcinoma (MTC). Here we report results of the phase IIB trial (ALTER01031, NCT02586350) of anlotinib for locally advanced or metastatic MTC with a larger samples. Methods: Between September 2015 and September 2018, 91 patients were enrolled in China. Eligible patients have diagnosed as phase IV MTC with relapsed and measurable disease and without antiangiogenetic target therapy. The patients were randomly assigned in a 2:1 ratio to receive anlotinib or a matched placebo (12 mg QD from day 1 to 14 of a 21-day cycle). Patients who have been diagnosed with disease progression by the Independent Imaging Committee could be unblinded and crossed to the treatment group if the patient previous treated by placebo. The primary endpoint was progression-free survival (PFS). Results: 91 patients were randomized 62 to anlotinib arm and 29 to placebo arm. Until the data cutoff date (1 Feb 2019), median PFS was 20.67 months (95%CI, 14.03-34.63) in anlotinib arm vs 11.07 (95%CI, 5.82-14.32) months in placebo arm (HR 0.53, p = 0.0289). The OS data were not sufficiently mature for analysis. Considerable improvement in ORR was observed over the two arms (48.39% vs 3.45%, p &lt; 0.0001). The adverse events (AEs) were 100% in anlotinib arm and 89.66% in placebo arm. The most common AEs in anlotinib arm were hand-foot syndrome, hypertension, hypertriglyceridemia and diarrhea. Conclusion: ALTER01031 met its primary endpoint of PFS shows that anlotinib treatment is effective and well tolerated. The safety profile was consistent and no new adverse events were identified. These data potentially extend the role of anlotinib monotherapy as a new therapy strategy for MTC patients. Clinical trial information: NCT02586350.
Relationship of emergency department use pre- and post-cancer diagnosis in safety-net adults.
Authors: Arthur Hong, Navid Sadeghi, John Vernon Cox, Simon Craddock Lee, Ethan Halm
Journal: Journal of Clinical Oncology (2019)

6626 Background: Safety-net adults generate a high rate of emergency department (ED) visits within the 180 days after a new cancer diagnosis, many of which could be alternatively triaged to an urgent care clinic. It is unclear how much of this ED use is attributable to the cancer and treatment vs. ED-seeking behavior. To identify patients at risk of frequent ED use, we explored whether a patient’s pre-cancer ED visit use predicted ED use after diagnosis. Methods: We identifiably linked adults from the tumor registry in the Dallas County safety-net health system to a regional hospital database with claims-like data for all patients from 98% of non-federal hospitals in North Texas. We applied a mixed-effects multivariate logit model, using frequent ED use (≥4 visits) in the 6-12 months or 12-18 months before diagnosis to predict frequent ED use after diagnosis, adjusting for demographics, comorbidities; cancer type, stage, initial treatment modalities; and grouping visits at the patient level. Results: Of 8,610 adults diagnosed from 2012-2016, 76.2% had Medicaid or were uninsured, 30.9% had lung, breast, or colorectal cancer, and 25.9% had advanced-stage cancer at diagnosis. In the 180 days after diagnosis, 42.5% of patients had zero ED visits, 45.7% had 1-3 visits, and 11.8% were frequent ED users (≥4). In multivariate analysis, patients with frequent ED use in the 6-12 months before a cancer diagnosis had 6.7 higher odds (95% CI: 4.8, 9.3) of having frequent ED use after diagnosis, compared to patients who had zero ED visits prior to diagnosis. This compared to 1.3 higher odds (95% CI: 1.1, 1.5) of frequent ED use if the patient had advanced-stage cancer, and 2.1 higher odds (95% CI: 1.8, 2.4) if chemotherapy was part of initial treatment. Although most post-diagnosis frequent ED users generated zero visits (62.2%) or 1-3 visits (30.7%) in the 6-12 months prior to diagnosis, 38% of patients with frequent ED use pre-diagnosis continued frequent ED visits after diagnosis. Results were similar for ED use 12-18 months prior to diagnosis. Conclusions: Among safety-net adults, prior ED-seeking behavior strongly predicted ED use after a new cancer diagnosis. This may represent a high-risk group that might benefit from care delivery innovation.
Outcomes and toxicities in sarcopenic patients with metastatic solid tumors treated with check point inhibitors.
Authors: Laura Haik, Aurore Gonthier, Eric Frison, Marine Gross-Goupil, Charlotte Domblides, Remi Veillon, Amandine Quivy, Alain Ravaud, Amaury Daste
Journal: Journal of Clinical Oncology (2019)

e14166 Background: Evidence suggests that sarcopenia is a significant predictor of worst outcomes and treatment toxicities in metastatic solid tumors patients (pts). We investigated whether sarcopenia was associated with outcomes and severe toxicities (ST) in patients treated with check point inhibitors (CPI). Methods: All consecutive metastatic solid tumors patients treated with CPI from January 2013 to December 2017 in Bordeaux University Hospital (France) were retrospectively reviewed. Sarcopenia was evaluated using computed tomography (CT) obtained within 1 month before treatment initiation. Skeletal muscle mass index (SMI) were measured from axial L3 CT section. Sarcopenia was defined as SMI ≤ 52.4 cm 2 /m 2 for males and SMI ≤ 38.5 cm 2 /m 2 for women. Clinical characteristics included Performance Status (PS) and anthropometric parameters. ST included grade III-IV according to NCI-CTC v4.0 and any grade of toxicity leading to treatment interruption. Results: Among 261 pts included, 179 (69%) had metastatic lung cancer and 151 (58%) had previously received one line of treatment. Median age was 61 years old and there were 198 males (76%). PS status was 1 in 55% of pts. CPI treatment was: anti PD1, anti PD-L1, anti CTLA-4 and CPI combination in 192, 43, 3 and 20 pts, respectively. The prevalence of sarcopenia was 64%. At inclusion, sarcopenia was associated with poor PS (p = 0.002), anorexia (p &lt; 0.001), lower albumin (p = 0.002) and hemoglobin (p &lt; 0.001). Objective Response Rate (ORR) was 28% in sarcopenic pts and 26% in non-sarcopenic pts. Median progression free survival (PFS) was 6.9 and 7.6 months in sarcopenic pts and non-sarcopenic pts respectively (p = 0.5). In multivariate analysis, sarcopenia was not associated with PFS or ORR. Median overall survival (mOS) was 10.2 months in lung cancer, without significant difference between sarcopenic and non-sarcopenic patients (mOS: 9 months and 17 months respectively, p = 0.06). In general population, ST occurred in 36 (14%) pts; among which 23 (64%) presented sarcopenia. In multivariate analysis, sarcopenia was not associated with ST (OR = 1.16, p = 0.71). Conclusions: Sarcopenia was not associated with outcomes or toxicities in metastatic solid tumors patients treated with CPI in this study.
Prevalence and clinical implications of mismatch repair (MMR) deficiency in unselected non-serous epithelial ovarian cancer (EOC) patients (pts).
Authors: Mariana Scaranti, Krithika Murali, Cecilia Orbegoso, Katherine Vroobel, Susana N. Banerjee, Martin Eric Gore, Ayoma Attygalle, Angela George
Journal: Journal of Clinical Oncology (2019)

1521 Background: It has previously been reported that 6-7% of clear cell (CC) and endometrioid (E) ovarian cancers are MMR deficient (MMRd). The prevalence of MMRd in other histological subtypes and correlation with germline (g) MMR (Lynch Syndrome) mutations in unselected non-serous EOC pts is less clear. MMRd in solid tumors has been associated with enhanced response to immunotherapy, hence knowledge of MMR status has therapeutic and familial implications. We aimed to study the prevalence and implications of MMRd and gMMRd in unselected pts with non-serous EOC. Methods: Routine immunohistochemistry (IHC) was performed for the MMR proteins MLH1, MSH2, MSH6 and PMS2 in all non-serous EOC pts from June 2016; retrospective MMR IHC testing in pts in follow-up was performed. Pts with MMRd tumors were referred for gMMR testing. Results: We analyzed 66 unselected pts with non-serous EOC. Median age was 56.4 years (yrs). The majority had E ovarian cancer (54.5%) followed by CC (25.8%), mixed histology (12.1%), mucinous (4.5%) and mullerian (3%) subtypes. Endometriosis was noted in 45.5% of pts, and 75% were FIGO stage I and II at diagnosis. Seventeen pts (25.8%) had concurrent endometrial cancer, all Grade I. On IHC, 15.2% were MMRd: 5 E, 2 CC, 2 mixed and 1 mullerian-type. Of these, 3 pts (30%) had gMMR mutation, 2/3 did not meet the Revised Bethesda criteria for testing. A lower average body mass index (Kg/m 2 ) was noted in MMRd 25.9 versus 30.1 in MMR proficient (MMRp). Median age at diagnosis was 53.5 yrs in the MMRd and 57.7 yrs in MMRp. A higher frequency of concurrent endometrial cancer was observed on the MMRd group (60%) versus (20%) on MMRp (p = 0.007). No statistically significant difference in overall survival or disease-free survival was observed between the MMRd and MMRp population. Conclusions: Our study has shown a higher prevalence of somatic MMRd in non-serous EOC (15.2%) than in previously published literature with a significant proportion found to carry gMMR mutations (4.5%). These interim findings support the role of universal MMR IHC testing in non-serous EOC regardless of family history. [Table: see text]
Immune profile of metastatic uveal melanoma during treatment with pembrolizumab.
Authors: Ernesto Rossi, Ilaria Zizzari, Giovanni Schinzari, Alessandra Di Filippo, Brigida Anna Maiorano, Tommaso Dosa, Monica Maria Pagliara, Emilio Bria, Maria Antonietta Blasi, Giampaolo Tortora, Marianna Nuti
Journal: Journal of Clinical Oncology (2019)

9536 Background: Metastatic uveal melanoma (mUM) is a rare and aggressive disease. No standard therapy has been established. All the available treatments derive from trials in cutaneous melanoma. A minority of patients with mUM can benefit from immunotherapy. Immunological features of a group of patients with metastatic UM treated with Pembrolizumab were analyzed in order to explore the immune-response in this disease and the potential factors able to select the patients who can benefit from immunotherapy. Methods: Blood samples from 12 UM patients before (T0) and during treatment with Pembrolizumab (T1: after 1 cycle of Pembrolizumab; T2: after 3 cycle of Pembrolizumab) were collected. Peripheral blood mononucleated cells (PBMCs) were isolated and characterized for markers expression. Sera were analyzed for a panel of soluble (s) immune checkpoints and cytokines. The correlation between immunological parameters with PFS and OS was explored. Blood samples from 6 metastatic cutaneous melanoma (CM) patients with a confirmed response to anti PD-1 agents were also collected during the treatment and analyzed for PBMCs and sera. Results: Soluble CTLA4, sPD-L1, sCD137, sTIM3 were significantly higher in UM than in CM. CD137 was significantly higher in UM patients progressed with Pembrolizumab than in the 2 responsive patients (512 pg/ml vs &lt; 12.9 pg/ml, respectively, p = 0.04) who are still alive and on treatment after a median follow-up of 24 months. Low sGITR, sCD137, sHVEM, and sTIM3 are associated with longer PFS. IL-8 was lower in CM than UM (2.5 pg/ml vs 40.7 pg/ml) and in the responsive versus progressed UM patients (3,7 pg/ml vs 118 pg/ml, p = 0,042). Low levels of IL-8 and IL-1-alpha are significantly associated with longer PFS (p = 0.011 and 0.010 respectively). In responsive patients CD137 expression on CD3+, CD4+ and CD8+ T cells was higher than in progressed patients, while sCD137 was absent. Conclusions: A group of s-immune checkpoints and cytokines correlate with Pembrolizumab effectiveness in mUM. High expression of CD137 on T cells associated with the absence of its soluble form in responders could suggest the correlation between the retention of this co-stimulatory molecule and efficacy of anti-PD1.
Comprehensive genomic profiling of circulating cell-free DNA (cfDNA) distinguishes focal amplification (amp) from aneuploidy among <i>MET</i> amps in diverse advanced cancer types.
Authors: Yuichi Kumaki, Sadakatsu Ikeda, Thereasa A. Rich, Jing Zhao, Takayuki Yoshino, Byoung Chul Cho, Nir Peled, Ji-Youn Han, Yukimasa Shiotsu, Aleksandra Franovic, Victoria M. Raymond, Razelle Kurzrock, Richard B. Lanman, Jeeyun Lee, Tony S. K. Mok
Journal: Journal of Clinical Oncology (2019)

3046 Background: MET amps can occur from focal gene copy number gain (e.g. MET-driven) or gain of chromosome 7 (e.g. aneuploidy); however, the contribution of each to MET amp is not well established. MET inhibitor-sensitive lung cancers harboring high-level MET amp have been reported in the absence of other sensitizing MET alterations (alts), e.g. exon 14 skipping, particularly among those with higher MET to chromosome 7 ratios. Methods: 3,114 samples from 2,902 Asian patients with advanced solid tumors were tested with a comprehensive cfDNA NGS panel (Guardant360) between Oct 2015-Dec 2018. This 70-73 gene assay evaluates single nucleotide variants (SNV), selected insertion-deletions (indels), fusions, and copy number gains. Focal amp was determined bioinformatically as having statistically higher copy number relative to other genes, such as BRAF, or CDK6, in the same chromosome arm. Results: MET alts associated with aberrant signaling were found in 223 pts (7.7%) with 18 different cancer types, most commonly lung (128/1,678), colorectal (36/349), and prostate (11/48). Among 223 pts, 189 pts (84.8%) had amps, 38(17.0%) had exon 14 skipping, and 8 (3.6%) had activating SNVs. 39.7% of MET amp was focal but differed by cancer type; highest prevalence was in gastroesophageal (80%) and lowest in prostate cancers (9%). Samples with focal MET amp had higher plasma copy number compared to those with non-focal MET amp (mean 5.8 vs. 2.5; p &lt; 0.0001) and lower total number of alts per sample (8.8 vs. 11; p = 0.0122). Focal MET amp was more common than non-focal MET amp among 419 EGFR mutated samples (6.9% vs. 3.8%, p = 0.05) suggesting focal MET amp may be biologically more relevant as a mechanism of EGFR TKI resistance. Conclusions: This is the first study to use cfDNA to examine focal vs. non-focal MET amp. Focal MET amp accounted for ~40% of all MET amps, was found in 2.6% of pts with diverse cancers, was associated with higher plasma copy number, and found in a higher proportion of EGFR mutated lung cancer samples. The ability to differentiate may be clinically relevant given higher MET to chromosome 7 ratios have been associated with improved therapeutic response.
Treatment outcomes in malignant pleural mesothelioma: A single center experience of systemic therapies and biomarkers.
Authors: Adithya Balasubramanian, Adrian Pick, Beena Kumar, Zdenka Prodanovic, Prashant Joshi, Muhammad Alamgeer
Journal: Journal of Clinical Oncology (2019)

e20070 Background: Malignant Pleural Mesothelioma (MPM) is a rare but fatal disease related to asbestos exposure, with historic survival in the order of 9 to 17 months. Chemotherapy is associated with only a modest benefit. The advent of immunotherapy has heralded significantly improved outcomes using checkpoint inhibitors in an as yet ill-defined cohort. We aim to identify predictive and prognostic biomarkers in a series of patients (pts) with MPM and describe survival data. Methods: A retrospective audit was undertaken of pts with MPM diagnosed between 2013 and 2017 at a single tertiary centre in Melbourne, Australia (Monash Health). Data relating to patient outcomes and clinicopathological features were obtained through medical reports. Further immunostains are being performed on archived tissue for PDL-1 status. Results: 65 pts were identified, of whom 52 (80.0%) were male. Median age was 73 years (range 44-90). 52 pts were noted to be ECOG 0-1. 42 pts (64.6%) were noted to have suspected asbestos exposure. Epithelioid MPM was the most common subtype, noted in 41 pts (63.1%) (table 1). 8 pts (12.3%) presented with stage IV disease. 16 pts (24.6%) received checkpoint inhibitor therapy, with 10 (63 %) in the second/third line setting. Median overall survival (OS) was 19.8 months (95% CI 13.3-26.3) in the whole cohort.Patient characteristics associated with poor OS were: presence of weight loss (P = 0.001), chest pain (p = 0.08) and ECOG 2 (p = 0.04). Pts with sarcomatoid histology who received immune checkpoint inhibitors in any line of treatment had significantly prolonged OS compared to other histologies. 3-year survival was 80% in this group while median OS was not reached (p = 0.04). This difference was not seen with other histologies. Conclusions: The evolving landscape of treatment in MPM appears to show promise in improving OS. In this unselected case series, our data is consistent with historic controls in terms of survival and prognostic factors. The finding of significantly improved survival with immune checkpoint inhibitors in the sarcomatoid histology is exciting and warrants further exploration. Further data on PDL1 status will be presented.
Clinical haematological biomarkers: Derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) and their relationship to survival outcomes in non small cell lung cancer (NSCLC) treated with immunotherapy: A multicenter review.
Authors: Colum Dennehy, Eileen McMahon, Derek Gerard Power, Seamus O'Reilly, Dearbhaile Catherine Collins, Deirdre O'Mahony, Anne M. Horgan, Miriam O'Connor, Emmet Jordan, Paula Calvert, Richard Martin Bambury
Journal: Journal of Clinical Oncology (2019)

e20704 Background: Efficient use of immunotherapy in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. Recently considerable efforts have been invested to develop biomarkers to predict which patients should receive immune checkpoint inhibitors. This retrospective cohort study aimed to determine whether clinical factors and inflammation-based biological markers such as pre-treatment derived neutrophils to lymphocytes (dNLR) ratio, platelets to lymphocytes (PLR) ratio and prognostic nutritional index (PNI) were associated with outcomes in NSCLC patients treated with immunotherapy. Methods: This study was a multicentered, retrospective systematic review. Clinical and electronic records were retrospectively examined from metastatic NSCLC patients treated with immunotherapy from August of 2015 to September 2018 in 2 regional cancer centers and a total of 69 patients were enrolled. NLR ≥5 and PLR ≥260 were defined as elevated and PNI ≤35 was defined as reduced. Results: Approximately, 57% of patients had NLR ≤ 5 and 51% had PLR ≤260. We found utilising univariant analysis, that pretreatment NLR ≤ 5 was independently associated with superior OS (median 12.4 vs. 6.8 months; HR 2.13, 95% CI 1.66-2.6; p = 0.007) and PFS (median 3.55 vs. 2.6 months; HR 1.75, 95% CI 1.18-2.32; p = 0.024). Results were similar when examining PLR ≤260 median OS 13.64 vs. 7.36 months; HR 1.92, 95% CI 1.1-3.5; p = 0.028) The optimal cutoff for PNI was designated to be 35. The majority (87%) had PNI &gt; 35. NSCLC patients with PNI &gt; 35 were found to have significantly higher median OS compared to patients with PNI ≤35 (11.11 vs. 2.4 months; HR 5.36, 95% CI ; p = 0.001). Conclusions: Immunotherapy is considered as an effective new method to treat advanced NSCLC. In this cohort of patients pretreatment NLR &lt; 5,PLR &lt; 260 and PNI &gt; 35 were associated with superior outcomes. It is unclear whether these markers are predictive or prognostic or both.
Correlation betwen MKK4 expression (exp) and clinicopathological features, KRAS/NRAS mutation in metastatic colorectal cancer (mCRC).
Authors: Mutlu Dogan, Servet Guresci, Fahriye Tugba Kos, Oznur Bal, Yakup Ergun, Onder Bozdogan
Journal: Journal of Clinical Oncology (2019)

e14500 Background: We aimed to evaluate correlation between MKK4 exp &amp; clinicopathological features in mCRC Methods: MKK4 exp was assessed by immunoreactive score (IRS). Staining intensity [0 (no), 1+ (weak), 2+ (moderate), 3+ (strong)] &amp; % of positively stained cells [0 (0%), 1( &lt; 10%), 2 (11-50%), 3 (51-80%), 4 ( &gt; 80%)]. IRS was calculated by this formula (IRS = SI × PP). Cut-offs were explored with ROC analysis. AUC was 0.629 (95%CI:0.419-0.840) &amp; best cut-off value for MKK4 was 2.5 (sensitivity of 68 %). Groups were WIR ('weak'; IRS:0-2) &amp; SIR ('strong'; IRS ≥3). Results: We enrolled 95 patients. Median follow-up was 31.4 months. MKK4 exp strength outcomes are shown in table. K-ras/N-ras mutation rate was 45.2%. WIR patients had longer OS (p: 0.03). In WIR group, metastatic ones at diagnosis had shorter DFS (p:0,05). There was no PFS difference (p: 0,15). In correlation analysis, there was a a negative correlation between MKK4 expression &amp; 1st line treatment resistance, k-ras/n-ras mt, OS, PFS, DFS (r: -0.01; r: -0,06; -0,02; -0,10; -0,06; -0,34) ( p:0,04 for DFS). Conclusions: MKK4 exp inversely correlates with survival outcomes &amp; ras mutation. WIR leads longer DFS &amp; OS. [Table: see text]