tbuckley/cabot-search huggingface dataset:
Development and validation of nomograms to provide individualized predictions of survival benefits from surgery in patients with intermediate/advanced hepatocellular carcinoma.
Authors: Xin-Fei Xu, Ju-Dong Li, Jiong-Jie Yu, Hao Xing, Zheng Wang, Jun Han, Ming-Da Wang, Chao Li, Han Zhang, Han Wu, Wen-Tao Yan, Jia-He Wang, Bing Quan, Ya-Hao Zhou, Wei-Min Gu, Hong Wang, Ting-Hao Chen, Feng Shen, Meng-Chao Wu, Tian Yang
Journal: Journal of Clinical Oncology (2018)

e16112 Background: According to the BCLC treatment guidelines, surgery is not recommended for intermediate/advanced hepatocellular carcinoma (HCC). In real world, however, liver resections are often performed in patients with intermediate/advanced but resectable HCC, especially in the East. Methods: We retrospectively evaluated multicentric data of 1,325 patients newly diagnosed with intermediate/advanced HCC who underwent curative resection. We randomly divided the subjects into development (n = 875) and validation (n = 450) samples. Multivariate Cox proportional hazards models were developed and separately validated on the basis of patients’ clinicopathological variables assessed for associations with 1-year recurrence and 3-year mortality. The discriminatory accuracy of these models was compared with conventional tools by analyzing receiver operating characteristic (ROC) curves. Results: The statistical nomograms built based on performance status, Child-Pugh grade, portal hypertension, preoperative alpha-fetoprotein level, tumor rupture, largest tumor diameter, tumor number, macrovascular and microvascular invasion, and satellites had good calibration and discriminatory abilities, with c-indices of 0.70 (1-year recurrence) and 0.68 (3-year survival), respectively. These models showed satisfactory goodness-of-fit and discrimination abilities in the validation cohort (c-index, 0.68 for 1-year recurrence and 0.69 for 3-year survival). The areas under the ROC curve using these nomograms exceeded those of traditional staging systems, indicating superior discriminatory capability (c-indices, 0.60-0.63 and 0.56-0.62, respectively). Conclusions: Our proposed online nomograms, which present graphically postoperative prognostic models for recurrence and survival in patients with intermediate/advanced but resectable HCC, offer valuable guidance to surgeons and hepatologists for individually predicting survival benefits from surgery and planning recurrence surveillance and adjuvant therapy.
Interleukin-31 and itch in dermatomyositis
Authors: H.J. Kim, M. Zeidi, D. Bonciani, S.M. Pena, J. Tiao, S. Sahu, V.P. Werth
Journal: British Journal of Dermatology (2018)

Patients with dermatomyositis often suffer from itching, but the mechanism is unknown. The authors of this study, based in USA, Korea and Italy, aimed to find out how common itch is in patients with dermatomyositis, and whether a cytokine called IL‐31 is increased in affected skin. Cytokines are proteins produced by cells in the immune system and a delicate balance of cytokines is needed to maintain health. In some skin disorders, such as atopic eczema, this balance is disrupted, and too many pro‐inflammatory cytokines (meaning ones which cause inflammation) are produced. 191 patients with the condition were surveyed, and the authors took biopsy samples from skin lesions, compared with four healthy controls (people without dermatomyositis). They found that half of the patients had moderate to severe itch, and itch was linked to the severity of the disease. In skin lesions from patients with itchy dermatomyositis, there was increased gene expression of IL‐31and its receptor (meaning more IL‐31 and the receptor that helps it work were released), and this expression was stronger in patients with more severe itch. A new drug under investigation for dermatomyositis, lenabasum, reduces or ‘downregulates’ the expression of IL‐31, and the authors conclude that it may prove to be of value in the treatment of itch in this condition.
Assessment of concerns and distress during the survivorship summary of care plan appointment.
Authors: Patricia A. Robinson, Christine B. Weldon, Sofia M Garcia, Carol A. Rosenberg, Stephanie Boecher, Julia Rachel Trosman, Javier Macias, Rosa Berardi, Laura Jane Hyde, Claudia Beth Perez, Seshan Subramanian, Frank J. Penedo
Journal: Journal of Clinical Oncology (2016)

e21558 Background: The IOM and CoC recommend survivorship distress screening and survivorship care plans for cancer patients. The Coleman Supportive Oncology Collaborative (CSOC) developed a tool for psychosocial; physical and practical concerns; and distress screening for concurrent use during the cancer survivorship visit. Methods: NCCN and CSOC (versions 1 and 2) distress tools were used in sequential patients (n = 60) who had completed their adjuvant therapy at a safety net hospital in Chicago, IL. The components of the CSOC v.1 screening tool were the PHQ4, practical problems, family concerns, spiritual/ religious concerns, nutrition concerns, and physical problems. Version 2 of the tool added fear of cancer recurrence and lifestyle factors. Results: The NCCN screening tool (version 2.2013) was administered to 44 patients. The mean score on the distress thermometer was 2.61 (range 0-10). The CSOC v.1 tool was administered to 4 patients. The CSOC v.2 tool was administered to 12 patients. The most common physical problems consistently identified on the screening tools were fatigue (52%, 75%, 66% respectively); tingling in hands/ feet (36%, 75%, 66% respectively). Specific to treatment on the CSOC v.2, 58% (n = 7) were concerned about long term complications; 41% (n = 5) acknowledge a lack of understanding about their cancer diagnosis or stage; 41% noted concerns about food and cancer risk and weight gain (n = 5). The most common physical problems included hot flashes and vaginal dryness (83%, n = 10). Forty-one percent noted exercising < 1 hour per week. The NCCN and CSOC v.2 tools identified that the most common practical problem was insurance/ financial (23%, 33% respectively). Conclusions: Results suggest that administering a comprehensive tool to assess concerns and distress at the time of the survivorship summary of care appointment is feasible and captures patient’s concerns that may otherwise remain unnoticed. Survivors continue to experience multiple concerns and distress, thus benefit from a comprehensive tool that is tailored to capture their unique survivorship needs. Administration of the tool at the beginning of the appointment provided the framework for the patient’s survivorship appointment narrative.
Phase Ib study of anti-mesothelin antibody drug conjugate anetumab ravtansine in combination with pegylated liposomal doxorubicin in platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer.
Authors: Iurie Bulat, Kathleen N. Moore, Alexei Haceatrean, John Woojune Chung, Prabhu Rajagopalan, Chenghua Xia, Dirk Laurent, Barrett H. Childs, Alessandro Santin
Journal: Journal of Clinical Oncology (2018)

5571 Background: Anetumab ravtansine (AR) comprises a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. A phase Ib dose escalation was conducted in patients with platinum-resistant ovarian cancer to assess overall safety, pharmacokinetics (PK) and clinical activity. Methods: Eligible pts with histologically confirmed, locally invasive or metastatic platinum-resistant ovarian cancer, and ECOG performance status ≤1 were enrolled. Pegylated liposomal doxorubicin (PLD) at 30 mg/m2IV every 21 days (q3w) was administered with AR in two IV dosing schedules: 5.5 or 6.5 mg/kg q3w in 9 pts (Part I dose escalation) and at 6.5 mg/kg q3w in 12 patients (Part II expansion cohort). Tumor response was assessed based on RECIST v1.1 q6w C1-C9 and q12w thereafter. Determination of mesothelin expression in archival or fresh biopsy tumor samples by IHC (SP74, Ventana) was highly encouraged. PK of AR and PLD was performed. Results: A total of 21 pts were evaluable in Part I and II: mean age 61.5 yrs (range 42-77), PS 0/1 66.7%/33.3%, median prior lines of therapy 3 (range 1-10). The maximally tolerated dose (MTD) in combination was AR at 6.5 mg/kg and PLD at 30 mg/m2 q3w. Adverse events (AEs) were similar to previously reported AEs for of each agent as monotherapy, including reversible corneal disorders, neutropenia, liver function test increases and gastrointestinal disorders. Drug-related (DR) serious AEs were low (2 pts, 9.5%). Most common grade 3-4 AEs were neutrophil count decreased (5, 23.8%) and platelet count decreased (2, 9.5%). A total of 11 pts (52%) had confirmed partial responses (PR) and 7 (33%) had stable disease for a disease control rate of 86%. Six pts (29%) had a durable PR ( > 250 days). No PK interaction was observed. Conclusions: AR in combination with PLD showed preliminary efficacy with durable PRs in pts with platinum-resistant ovarian cancer. The safety profile was manageable. Further study of this combination is warranted. Clinical trial information: NCT02751918.
Prevalence of microsatellite instability and association with pembrolizumab (P) usage in a real-world clinico-genomic database.
Authors: Claire O'Connell, Daniel Backenroth, Gaurav Singal, Vineeta Agarwala, Gerald Li, Gaurav Kaushik, Garrett Alpha Cobb, Chun-Kai Kao, Vincent A. Miller, Amy Pickar Abernethy, Kenneth Robert Carson
Journal: Journal of Clinical Oncology (2018)

e15072 Background: In May 2017, the FDA approved for the first time a cancer therapy (P) for use in patients based on the presence of a genomic marker (microsatellite instability-high, or MSI-H) instead of tissue of origin. The real-world prevalence of MSI-H and the impact of the FDA approval on P treatment patterns is not well characterized. Methods: We performed a retrospective study of patients in the Flatiron Health (FH) network ( > 265 oncology practices across the U.S) from Jan 2011 to Sept 2017, who received FoundationOne tumor sequencing as part of routine clinical care. Tumor type was determined by pathologist review of specimens sent to Foundation Medicine. Treatment data was curated from FH's electronic health record-derived database. MSI was assessed using DNA sequencing across 395 genes. Fisher’s exact test was used for statistical comparisons of P use after FDA approval in MSI-H v. non-MSI-H patients and P use in MSI-H patients pre- and post- FDA approval. Results: Among patients with known MSI status (n = 14,944), 251 (1.7%) had MSI-H tumors. Tumor-specific rates of MSI-H varied by histology: 14.2% in endometrial cancer, 5.5% in colorectal cancer (CRC), 5.2% in other gastrointestinal (GI) cancers, and < 0.5% in breast and non-small cell lung cancer. Among the 34 MSI-H patients treated with P, CRC was the most common tumor type (35.3%), followed by stomach cancer (17.6%), and > 10 others. Among immune checkpoint inhibitor (ICPI)-naive patients with tumor types in which P was not indicated prior to the MSI-H approval, usage post-approval was higher in MSI-H patients (5.2%) than non-MSI-H patients (0.6%) (OR = 9.8; 95% CI 4.6-19.2; p < 0.001). Among MSI-H patients, we found no evidence that rates of first exposure to P differed 4 months pre- v. post-approval (13.4 v. 18.1% ; p = 0.5). Conclusions: Evidence of MSI-H is rare outside of endometrial, CRC, and GI cancers. Among tumor types in which P was approved only for MSI-H patients, usage was higher in MSI-H v. non-MSI-H patients post-approval. Longer follow up will determine the extent and trajectory of adoption, and additional clinical outcome data will characterize the effectiveness of ICPI agents among MSI-H patients treated in routine practice.
Efficacy and safety of alectinib in <i>ALK+</i> non-small-cell lung cancer (NSCLC): Pooled data from two pivotal phase II studies (NP28673 and NP28761).
Authors: James Chih-Hsin Yang, Sai-Hong Ignatius Ou, Luigi De Petris, Shirish M. Gadgeel, Leena Gandhi, Dong-Wan Kim, Fabrice Barlesi, Ramaswamy Govindan, Anne-Marie C. Dingemans, Lucio Crino, Hervé Lena, Sanjay Popat, Jin Seok Ahn, Eric Dansin, Sophie Golding, Walter Bordogna, Bogdana Balas, Peter N. Morcos, Ali Hassan Zeaiter, Alice Tsang Shaw
Journal: Journal of Clinical Oncology (2016)

e20507 Background: Alectinib is a highly selective inhibitor of ALK and RET tyrosine kinase, with proven systemic and CNS activity in ALK+ NSCLC. Results of two single-arm, open-label phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]) led to FDA approval of alectinib for patients (pts) with ALK+ NSCLC who progressed on or are intolerant to crizotinib. This pooled analysis further explored the efficacy and safety of alectinib in ALK+ NSCLC. Methods: Pts ( ≥ 18 yrs; locally advanced or metastatic ALK+ NSCLC [by FDA-approved FISH test]; progressed on or intolerant to crizotinib) received alectinib 600mg p.o. BID until progression, death or withdrawal. Crizotinib was the only prior ALK inhibitor permitted. This pooled analysis assessed objective response rate (ORR; RECIST v1.1) by independent review committee (IRC; primary endpoint); ORR by investigator; disease control rate (DCR); duration of response (DOR); progression-free survival (PFS); overall survival (OS); and safety. Results: The pooled dataset included 225 pts. The response-evaluable population by IRC included 189 pts (84%); 77% had received prior chemotherapy; 60% had baseline CNS metastases. Median follow-up was 12.8 months (27 Apr 2015 cut-off). CNS data have been presented previously (Gadgeel et al, WCLC 2015). Alectinib achieved an ORR by IRC of 51.3% (95% CI 44.0–58.6; all partial responses), a DCR of 78.8% (95% CI 72.3–84.4), with a median DOR of 13.2 months (95% CI 10.9–NE) based on 42% of events. Median PFS was 8.2 months (95% CI 6.3–11.3) based on 61% of events; 6-month OS rate was 85.2% (95% CI 80.6–89.9; median not reached). Efficacy by clinical subgroups will be presented. Grade 3–5 adverse events (AEs; any cause) occurred in 35% of pts, most frequently dyspnea (4%), increased blood CPK (4%), increased ALT (3%), and increased AST (3%). Alectinib was well tolerated, with 31% dose interruptions/modifications and 6% withdrawals due to AEs. Conclusions: This pooled analysis confirmed that alectinib achieves durable systemic responses and is well tolerated in crizotinib-refractory ALK+ NSCLC. A phase III trial of first-line alectinib vs crizotinib has completed accrual. Clinical trial information: NCT01801111, NCT01871805.
Paclitaxel (PTX) dose individualization by exposure optimization in Chinese patients with advanced non small-cell lung cancer (NSCLC) receiving first-line paclitaxel-carboplatin (PC) chemotherapy.
Authors: Jie Zhang, Huiwei Qi, Caicun Zhou, Huijuan Ni, Yunying Li
Journal: Journal of Clinical Oncology (2015)

8052 Background: PC chemotherapy is complicated by febrile neutropenia in up to 5% of patients with advanced NSCLC. PTX pharmacokinetic (PK) variability is a major factor in severe neutropenia. The time above a PTX plasma concentration of 0.05μmol/L (TC > 0.05) is the key PK parameter to measure systemic exposure to the drug and is a predictor of severe neutropenia. Optimization of an individual’s dose by exposure measures may improve PTX safety and efficacy. A randomized controlled study in Chinese NSCLC patients was performed to assess impact of PK-guided PTX dosing on safety and efficacy. Methods: To date, 141 stage IIIB/IV NSCLC patients receiving first-line PC chemotherapy have been enrolled. Patients are randomized to receive 4-weekly carboplatin (AUC = 5) plus paclitaxel at a starting dose of 175 mg/m2 with subsequent PTX dosing based on body surface area (BSA) or PK-guided dosing to target a PTX TC > 0.05 between 26 and 31 hours. Primary objective is to compare severe toxicities and response rates between BSA and PK arms. Results: Exposure values from 1st cycle in 90 patients show great PTX PK variability, with a mean TC > 0.05 of 36 hr (range = 26 - 46 hr, CV = 27%). 14% of these patients had PTX exposure values within the target range (26 to 31 hr) while 86% were above target exposure. No patient showed PTX exposure below target at standard PTX dose of 175mg/m2. Severe neutropenia rate for patients above exposure target was higher than those in target (grade 3 & 4 neutropenia of 31% vs 60%, grade 4 neutropenia of 0% vs 18%, respectively). Exposure optimization of PTX in PK arm leads to an overall 21% dose reduction. In 51 patients with 4 cycles of chemotherapy completed, severe neutropenia rate in PK arm at cycle 4 was 39% compared to 61% in BSA arm (p = 0.026). Response rate was also evaluated and showed no negative impact (24% PR rate in PK arm vs 16% in BSA arm). A higher neuropathy rate was observed in BSA arm (77%) compared to PK arm (42%). Conclusions: With exposure optimized PTX dose, severe neutropenia can be significantly reduced with no negative impact to clinical outcome.
Efficacy and safety of moxetumomab pasudotox (moxe) in adult patients (pts) with relapsed/refractory hairy cell leukemia (HCL) in relation to drug exposure, baseline disease burden, and immunogenicity.
Authors: Denison Kuruvilla, Yen Lin Chia, Linda Santiago, Kemal Balic, Nai-Shun Yao, Robert J. Kreitman, Ira Pastan, Xia Li, Meina Liang, Chih-Ming Tseng, Raffaella Faggioni, Lorin Roskos
Journal: Journal of Clinical Oncology (2018)

7060 Background: Moxe is an immunotoxin targeting CD22 on B cells leading to cell death. The objectives of this analysis were to characterize the pharmacokinetics (PK) and evaluate the exposure-efficacy/safety of moxe in pts with HCL. Methods: Data from two HCL studies (Ph1: 49 pts dosed at 5, 10, 20, 30, 40 & 50 µg/kg IV; Ph 3: 80 pts dosed at 40 µg/kg IV) were pooled to develop a population PK model. The model derived Cmax and AUC were then used to evaluate the exposure-efficacy/safety relationship in the 2 studies independently due to differences in bioactivity of materials (Ph1 50 µg/kg was bioactive equivalent to Ph3 40 µg/kg). Efficacy endpoints included complete response (CR), durable CR (Ph3 only) and objective response rate (ORR). Safety parameters included hemolytic uremic syndrome (HUS), capillary leak syndrome (CLS), ≥Gr 2 increased creatinine (CRE), and Gr 3/4 adverse events (AE). Results: Moxe PK was linear from 5-50 µg/kg with PK well-described by a 1-compartment model. Day 1 clearance (CL) was higher than for later doses (22 vs 4 L/hr), attributed to CD22+ B cell depletion with repeated dosing. Ph3 pts with anti-drug antibody (ADA) titers > 10240 had ~4-fold increase in CL. High CL was associated with high baseline B cells. High baseline B cells/low PK were associated with lower response rate, but clinical benefit was still observed. In Ph3, rates of CR and durable CR were 56-58% and 50-53% in high (≥median) PK exposure group vs 31-34% and 14-17% in the low PK exposure group. In Ph1, rate of CR was 67-71% in high vs 46-50% in low PK exposure groups. Pts with ADA titer > 10240 had lower CR and durable CR, but clinical benefit was still observed. Pts with high PK exposure had higher incidence of CLS and CRE in Ph3 but not in Ph1. HUS incidence in both studies was low and was not evaluated further. Pts with high PK exposure in Ph1 had higher rates of Gr 3/4 AE. Incidence of Gr 3/4 AE in Ph3 40 µg/kg was consistent with that of Ph1 50 µg/kg. Conclusions: Moxe CL decreased with repeated dosing, consistent with B cell depletion. ADA titer > 10240 increased CL by ~4-fold. Pts with high PK exposure had better response but had a slightly higher incidence of Gr 3/4 AE. Clinical trial information: NCT01829711 and NCT00586924.
Abstract 15168: The Impact of Normal Saline Infusion on Myocardial Deformation: Mechanistic Insight Into the Frank-Starling Law
Authors: Lin Wang, Stephanie K Isaacs, Merideth S Weiner, Arthur E Weyman, Michael H Picard, Aaron L Baggish, Rory B Weiner
Journal: Circulation (2013)

Background: The Frank-Starling Law states that cardiac stroke volume increases in response to increase in left ventricular (LV) end-diastolic volume (preload). Analysis of novel, sensitive markers ...
Stage at presentation for incarcerated patients at a single urban tertiary care center.
Authors: Kathryn S. Ivy, Kevin N. Griffith, Amy K. Rosen, Stephanie D. Talutis, David B. McAneny, Matthew H. Kulke, Jennifer F. Tseng, Teviah E. Sachs
Journal: Journal of Clinical Oncology (2018)

e18649 Background: As with many high risk vulnerable patient groups, incarcerated patients with cancer have worse outcomes and mortality than the general population; the reasons for which are poorly understood. We examined whether stage at presentation differed between incarcerated patients (IP) and the general population (GP) with cancer at an academic medical center with a disadvantaged patient population. Methods: We identified all patients presenting to our institution (01/01/2010 – 12/31/17) with a new diagnosis of cancer. Incarceration was identified by insurance billing records. Patients were compared on demographics, type of cancer and stage at presentation. Propensity score matching was used to adjust for demographic differences between IP and GP groups, with group outcomes compared using paired t-tests or Fisher exact tests. Surveillance, Epidemiology and End Results (SEER) data were used for regional data (RD) comparisons. Results: We identified 2950 patients, of whom 94 (3.2%) were IP. Demographics were similar between groups, although IP were more likely to be male (91% v 55%, p < 0.01) and of younger age (mean 53.1 vs 59.4, p < 0.01). The prevalence of specific cancers varied between groups (IP: hepatobiliary, bronchopulmonary, oropharyngeal, vs. GP: oropharyngeal, bronchopulmonary, prostate). Overall, IP were diagnosed at later AJCC stages than GP (p = 0.03), with IP more likely to present at stage 2 or later (73% vs 60%, p = 0.04). While stage at diagnosis was similar for bronchopulmonary cancer, IP with hepatocellular cancer (HCC) were more often stage 2 or greater (83.3% vs. 52.8%; p = 0.03). Nodal status was higher for IP for both HCC (N1: 17.6% vs. 2.9%; p = .20) and lung cancer (≥N2: 55.6% vs. 42.4%; p = .50), although these did not achieve statistical significance. Conclusions: IP with cancer are at higher risk for later stage presentation and, therefore, potentially worse outcomes and survival than GP and RD. This difference is particularly strong in patients diagnosed with HCC, a malignancy amenable to screening. Despite the small sample size, this study suggests that IP are a high-risk group who may benefit from earlier and/or more targeted screening to allow for timelier diagnosis and potentially improved survival.