tbuckley/cabot-search huggingface dataset:
Safety of histamine H2 blocker concomitant administration in patients treated with high dose methotrexate regimen.
Authors: Yun Jung Choi, Ji Sung Lee, Tae Won Kim, Cheolwon Suh, Dok Hyun Yoon, Jeong Eun Kim
Journal: Journal of Clinical Oncology (2016)

e21643 Background: Despite its effectiveness proven in a wide range of oncologic malignancies, use of high dose methotrexate (MTX) regimen is limited by potentially lethal non-hematologic toxicities. Renal and hepatic impairment, intestinal mucositis and peptic ulcers are well-known toxicities of MTX, and proton pump inhibitor (PPI) has been prescribed as prophylaxis of gastrointestinal injury. Although no formal studies have been conducted, histamine H2 blocker (H2B) is gradually substituted for a PPI, as there is evidence to suggest that the concomitant use of PPI with MTX may decrease MTX clearance, possibly contribute in MTX toxicities. The aim of this study was to confirm the safety of H2B concomitant administration and identify predictive factors for non-hematologic toxicities. Methods: Data of patients diagnosed with primary CNS lymphoma or osteosarcoma, treated with MTX 3,500 mg/m2 plus cytarabine or MTX 8,000 mg/m2 plus doxorubicin, cisplatin regimen, respectively, were retrieved. Age, sex, cancer type, concomitant administration of drugs reported to delay MTX clearance and H2B were selected as independent variables. Predictive factors for toxicities were analyzed using a univariate and/or multivariate logistic regression model. Results: A total of 1,098 cycles (179 patients) was analyzed. The results of univariate analysis demonstrated that age greater than or equal to forty, concomitant administration of penicillins, proton pump inhibitors, presence of MTX delayed elimination and primary CNS lymphoma compared to osteosarcoma was associated with higher risk of developing grade 2-4 nephrotoxicity. The presence of MTX delayed elimination was the only risk factor identified for oral mucositis. In multivariate analysis of grade 3-4 hepatotoxicity, osteosarcoma compared to primary CNS lymphoma was shown to possess higher risk. Interestingly, concomitant administration of histamine H2 receptor antagonist (H2B) was associated with lower risk of developing hepatotoxicity (OR: 0.26, 95% CI: 0.165-0.405, P< 0.001). Conclusions: Concomitant administration of H2B was shown to be safe. Further prospective study to evaluate the hepatoprotective effect of H2B is warranted.
Preselection of lung cancer cases using FGFR1 mRNA and gene copy number for treatment with ponatinib.
Authors: Terry L. Ng, Hui Yu, Derek Smith, Theresa A. Boyle, Emily R. York, Scott Leedy, Dexiang Gao, Lynn Heasley, Fred R. Hirsch, D. Ross Camidge
Journal: Journal of Clinical Oncology (2018)

12095 Background: NSCLC and SCLC cell line data suggested high FGFR1 mRNA levels and FGFR1 amplification (FGFR1-AMP) could predict sensitivity to FGFR TKIs. Overlap with KRAS mutations did not preclude TKI sensitivity. Ponatinib is a multi-kinase inhibitor of ABL, RET and FGFR1-4. Methods: Metastatic EGFR- and ALK-negative lung cancers were pre-screened for FGFR1-mRNA by in-situ hybridization (ISH) and FGFR1-AMP by silver in-situ hybridization (SISH). Initial positivity cutpoints were based on cell line sensitivity at predicted ponatinib exposure. ISH and SISH positive cases were offered treatment with ponatinib at 45 mg QD. Differences in overall survival (OS) between cohorts were assessed using log-rank test. Association of FGFR1 positivity with clinicopathologic features were assessed using Fisher's exact test and Kruskal-Wallis rank sum test. Results: From 2013-2017, 171 cases were prescreened (123 SISH and 126 ISH samples reported): 9/123 (7.3%) were SISH+; 53/126 (42.1%) were ISH+; 6 were concordantly positive for SISH and ISH. At the initial cutpoint, no specific correlations with age, sex, smoking status, or response to platinum therapy were identified. However, SISH+ cases had fewer coincident KRAS mutations (p = 0.03) than SISH- cases, and ISH+ cases had worse OS (p = 0.020) than ISH- cases. Exploring data for natural higher cutpoints did not alter SISH positivity but did suggest a higher cutpoint for FGFR1 ISH (≥ 20% dot cluster [23% [29/126] cases]), associated with SCLC histology (p = 0.022), soft tissue metastases (p = 0.050) and shorter OS (p = 0.031). Four patients received ponatinib: All were FGFR1 ISH+ by the initial cutpoint (≥ 1% dot cluster), 2/4 were ISH ≥ 20% dot cluster, and 1/4 was SISH+. Tolerability was poor. The best response for the two ISH ≥ 20% cases was SD and for the two ISH ≥ 1% cases, it was PD (ORR 0%, DCR 50%). Conclusions: High FGFR1-mRNA is more common than FGFR1-AMP and was associated with worse OS. Higher levels of FGFR1 mRNA may be associated with a specific phenotype and is worthy of further exploration. Ponatinib's poor tolerance suggests further FGFR exploration in ISH+ cases should utilize more selective FGFR1 inhibitors. Clinical trial information: NCT01935336.
Efficacy and safety profile of PD-1 and pdl-1 inhibitors in African American patients.
Authors: Shahla Bari, Sanjay R Jain, Rathi Narayana Pillai
Journal: Journal of Clinical Oncology (2018)

e15080 Background: The African American (AA) population has been under-represented in clinical trials for PD-1/PDL-1 inhibitors, constituting less than 5% of patients in these trials. Therefore, differences in the efficacy and safety profile in this patient population remains unknown. In our study we characterize our experience with the use of PD-1/PDL-1 inhibitors in the treatment of AA cancer patients at Grady Memorial Hospital which has a significant proportion of AA patients. Methods: We reviewed the charts of patients treated at our cancer center between 2015-2017 and identified patients who treated with any PD-1 or PD-L1 inhibitor, including Nivolumab, Pembrolizumab, Atezolizumab and Durvalumab. We assessed clinical characteristics, response, survival, and toxicities. Results: 88 patients had complete data and were eligible for analysis. There were 57 males and 31 females with a median age of 62 years. Lung cancer was the most common tumor type in 55 (63%) patients followed by head and neck 11 (13%), bladder 6 (7%), renal cell carcinoma 5 (5%). 64% of patients had stage 4 disease at diagnosis. Nivolumab was the predominantly used drug in 54 (61%) of patients followed by pembrolizumab in 21 (24%). PDL-1 expression testing was not done in 72 (82%) patients. 12 out of the 16 (75%) had greater than 50% PDL-1 expression in their tumor. Clinical benefit (stable disease, partial or complete Response) was seen in 57% in the nivolumab group and 61% in the pembrolizumab group and was 58% in high PDL-1 expressors. Median duration of response was 23 weeks and 17 weeks in the nivolumab and pembrolizumab groups respectively. 42 patients had died at analysis of which 33 (79%) had not responded to therapy. 20 died due to disease progression while 11 died due to pneumonia which represented 26% of deaths. Fatigue (27%), hypothyroidism (16%) and pneumonia (16%) were the most common adverse effects. Conclusions: We report on the largest cohort of AA patients treated with PD-1/PDL-1 inhibitors. This group, typically under represented in clinical trials, showed a similar clinical benefit rate as reported in trials. There was also a high incidence of grade 5 pneumonia in our patient population. This calls for caution in selecting patients for therapy.
Integrated microbiome and metabolome analysis to reveal the interplay between commensal bacteria and metabolites in colorectal cancer.
Authors: Yanlei Ma, Xinxiang Li
Journal: Journal of Clinical Oncology (2018)

e15696 Background: Colorectal cancer (CRC) is a malignant tumor resulting in third highest morbidity of all cancers. Driven by host’s genetic make-up and environmental exposures, the gut microbiome and its metabolites have been implicated as the cause and regulators of CRC pathogenesis. We assessed the human fecal samples as non-invasive and unbiased surrogates for cataloging the gut microbiota and metabolome in CRC. Methods: Fecal samples collected from CRC patients (CRC group, n = 50) and healthy volunteers (H group, n = 50) were subjected to microbiome (16S rRNA sequencing) and metabolome (gas chromatography mass spectrometry, GC-MS) analysis. The datasets were analyzed individually and were integrated for combined analysis using various bioinformatics approaches. Results: Fecal metabolomic analysis allowed identification of 164 metabolites spread over 40 metabolic pathways in both groups. In addition, there were 42 and 17 uniquely identified metabolites specific to H and CRC groups, respectively. Sequencing efforts for microbial diversity revealed 1084 operational taxonomical units (OTUs) across the two groups, which displayed lower diversity of species in the CRC patients. Integrated analysis correlated CRC-associated microbes with metabolites such as polyamines (cadaverine and putrescine). Conclusions: Our results provide substantial evidence for the novel interplay between the gut microbiome and metabolome (i.e., polyamines), which is drastically perturbed in CRC. Microbe-associated metabolites can be used in the future as diagnostic biomarkers in therapeutic explorations.
The prognostic impact of sarcopenic change after 8 weeks of 1st line gemcitabine based chemotherapy in advanced pancreatic adenocarcinoma.
Authors: In-Ho Kim, Myung Ah Lee, Moon Hyung Choi, In Seok Lee, Tae Ho Hong, Eun-gyo Jeong
Journal: Journal of Clinical Oncology (2018)

e16237 Background: Sarcopenia has recently been acknowledged as the major component of cancer cachexia. We evaluate the prognostic impact of sarcopenic change after 8 weeks of first-line gemcitabine based chemotherapy in advanced pancreatic adenocarcinoma. Methods: We retrospectively analysed 253 patients who received first-line palliative gemcitabine based chemotherapy between 2010 and 2017. The measurement of the skeletal muscle area was performed using a software analysis system (Advantage Windows workstation 4.6, GE Healthcare, Milwaukee, Wisconsin, USA). Sarcopenia was defined as skeletal muscle index (SMI, cm2/m2) < 43.1 in males and < 36.3 in females using ROC curve. Results: Among 253 included patients, 54 (21.3%) patients were sarcopenic at diagnosis. The mean value of SMI decreased from 45.8 to 44.1 cm2/m2 after the 8 weeks chemotherapy for all patients (P < 0.001). The mean percent of SMI decrease was 3.3%. SMI decrease after chemotherapy was observed in 169 patients (all 67%, male 73%, female 56%). The initial sarcopenia group exhibited poorer overall survival (OS) and progression free survival (PFS) compared to the non-sarcopenia group (median OS, 5.2 vs 7.8 months, median PFS, 3.1 vs 3.9 months, all P < 0.001). Patients with SMI decrease (≥5%) from baseline showed poorer OS compared to the less SMI decrease ( < 5%) or increase group (OS, 5.7 vs 8.1 months, P = 0.032). Multivariate analysis showed that higher levels of CA 19-9 (P < 0.001), number of metastatic organs (P = 0.023), sarcopenia (P < 0.001), and decreased SMI after chemotherapy (P = 0.021) are poor prognostic factors for OS. Conclusions: Sarcopenia at diagnosis was a poor prognostic factor in patients with pancreatic adenocarcinoma. Also, skeletal muscle depletion during the chemotherapy was associated with negative outcome. The assessment of body composition and its change during the treatment process should be considered when treating patients with advanced pancreatic cancer. Overall survival HR 95% CI P CA19-9 < Median 1 ≥Median 2.9 1.7-5.2 < 0.001 Number of metastatic organs 0-1 1 ≥2 1.6 1.1-2.3 0.023 Sarcopenia at diagnosis No 1 Yes 2.4 1.5-3.9 < 0.001 SMI decrease < 5% 1 ≥ 5 % 1.9 1.1-3.4 0.021
Prognostic immune scoring of colorectal cancer liver metastasis with MHC class-I expression combined to T cell quantification.
Authors: David Henault, David Stephen, Pierre-Antoine St-Hilaire, Nouredin Messaoudi, Franck Vandenbroucke-Menu, Marylene Plasse, Richard Letourneau, Andre Roy, Michel Dagenais, Real W. Lapointe, Bich Nguyen, Genevieve Soucy, Anne-Marie Mes-Masson, Simon Turcotte
Journal: Journal of Clinical Oncology (2018)

3586 Background: Approximately 80% of patients recur after curative-intent resection of colorectal cancer liver metastasis (CRLM) and systemic chemotherapy. Immune profiling may help prognostication to individualize follow-up and lead to novel therapeutic strategies. We tested whether adding major histocompatibility class I (MHC-I) expression to T cell immune scoring in CRLMs could group patients with distinct prognosis. Methods: Tissue microarray analysis of 391 CRLMs resected in 214 patients (2011-2014) followed prospectively until 10/2017. Each CRLM arrayed with twelve 0.6 mm punch biopsies, 6 at the interface (IF) with normal liver and 6 intratumoral (IT). Automated quantification of CD3+ cells and MHC-I+ surface area stained by immunohistochemistry. We tested associations between immune, clinicopathological, and time to recurrence (TTR) and disease specific survival (DSS) outcome variables. Results: The mean patient age was 62.7 years, 78.5% received pre-operative chemotherapy (mean of 6 cycles), and a median of 2 CRLMs/patient were resected. The median TTR and DSS were 15.4 and 56.7 months, respectively. Pre-operative chemotherapy was associated with higher CD3 infiltration and lower MHC-I expression at IF and IT. Good pathological response to chemotherapy (Rubbia-Brandt TRG score 1-2-3) compared to lack of response (TRG 4-5) was associated with higher CD3 infiltration but no significant difference in MHC-I expression. CD3 immune scoring integrating the IF and IT areas had no prognostic value. MHC-I expression prognostically stratified patients with CD3low but not CD3high CRCLMs. Compared to the rest of the cohort, patients with at least one CD3lowMHC-Ihi CRLM (n = 35, 16.4 %) had significantly shorter median TTR (8.3 vs. 17.1 months, p < 0.001) and DSS (42.6 vs. 61.5 months, p < 0.001). CD3lowMHC-Ihi CRLMs were found in 41.2% of recurrent CRLMs in patients without this type of metastasis at first resection. CD3lowMHC-Ihi CRLM was an independent predictor of poor outcomes by multivariate analysis. Conclusions: CD3lowMHChi CRLMs may identify patients with poorly immunogenic tumors associated with worst outcome and suboptimal response to systemic chemotherapy.
Incidence of venous thromboembolism among patients receiving neoadjuvant chemotherapy for advanced ovarian cancer.
Authors: Julia Salinaro, Jessie Ehrisman, Angeles Alvarez Secord, Brittany Anne Davidson
Journal: Journal of Clinical Oncology (2018)

e17531 Background: Risk factors for VTE are well established and include active malignancy, impaired mobility and increasing age. In ovarian cancer (OC), women with extensive disease not amenable to optimal primary debulking or those with poor performance status (limited mobility, poor nutrition, comorbidities) may be offered neoadjuvant chemotherapy (NACT). Significant overlap exists between risk factors for VTE and indications for NACT among patients with OC. The objective of this study was to determine the incidence of VTE among women receiving NACT for OC. Methods: This was a retrospective cohort study of patients receiving NACT for primary OC, fallopian tube, or peritoneal cancer from January 2000 to December 2017 at our academic institution. Primary outcomes included rates of VTE at diagnosis and during NACT. Secondary outcomes included incidence of VTE following interval debulking surgery (prior to resuming treatment), during adjuvant CT and during treatment for recurrence. Results: One hundred twenty-six patients received NACT. Median age and BMI were 64.5 (range 35-88) and 26.3 (range 16-52.5), respectively. Sixteen patients presented with a VTE at diagnosis (12.7%). Of the remaining 110 patients, 5 (4.5%) had VTEs during NACT, all of whom were < 70 years old (range 41-68) and had a performance status of 0 or 1; the majority (4/5; 80%) were overweight or obese. Sixty percent were African American; the rest were diagnosed in Caucasian women. Two patients (1.8%) had a VTE post-operatively, 2 (1.8%) during adjuvant CT, and 7 (6.4%) with treatment for recurrence. Conclusions: In this series, most VTE in women receiving NACT were present at diagnosis, which may have been a factor in the decision for NACT. Though the rate of VTE during NACT was low, most (4/5) occurred in women who were either overweight or obese and/or African American (3/5). Larger studies are needed, but special consideration for VTE prophylaxis during NACT may be warranted for specific subsets of patients. Table 1. Patient demographics and VTE during NACT. Patient Demographic All (n = 126) VTE during NACT (n = 5) Age (y) < 70 85 5 ≥70 41 0 BMI < 25 49 1 30-40 41 2 30-40 28 1 <40 6 1 Race Caucasian 84 2 African American 24 3 Other 18 0 ECOG 0 31 2 1 49 3 2 12 0 3 6 0
Safety and efficacy of daratumumab-based regimens in elderly (≥75 y) patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Subgroup analysis of POLLUX and CASTOR.
Authors: Maria-Victoria Mateos, Andrew Spencer, Ajay K. Nooka, Ludek Pour, Katja C. Weisel, Michele Cavo, Jacob Laubach, Gordon Cook, Shinsuke Iida, Lotfi Benboubker, Saad Zafar Usmani, Sung-Soo Yoon, Nizar J. Bahlis, Christopher Chiu, Jordan Mark Schecter, Kaida Wu, Xiang Qin, David Soong, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2017)

8033 Background: Daratumumab (D) plus lenalidomide and dexamethasone (Rd; POLLUX) or with bortezomib and dexamethasone (Vd; CASTOR) demonstrated prolonged PFS and tolerability compared with Rd and Vd alone, respectively, in RRMM pts. We examined the safety and efficacy profiles of DRd and DVd in elderly (≥75 y) pts from these phase 3 studies. Methods: Pts with ≥1 prior line of therapy were enrolled. All pts in POLLUX were treated until progression; CASTOR pts received 8 cycles of Vd ± daratumumab. Different D (16 mg/kg) dosing schedules were used in POLLUX (qw for cycles 1-2, q2w for cycles 3-6, and q4w thereafter) and CASTOR (qw in Cycles 1-3, q3w for Cycles 4-8, and q4w thereafter). Elderly pts received a reduced dexamethasone dose (20 mg once weekly). Results: In POLLUX, 29/286 (DRd) and 35/283 (Rd) were ≥75 y, with 86% and 91% having ECOG status ≤1, respectively. With 17.3 months of median follow up, 10% in DRd and 11% in Rd discontinued due to treatment-emergent adverse events (TEAEs). Common (&gt;10%) grade 3/4 TEAEs for DRd included neutropenia and hypokalemia (Table). Twelve (41%) DRd pts experienced infusion-related reactions (IRR) and 4 (14%) experienced grade 3/4 IRR; none discontinued due to IRR. Median PFS was not reached (NR) in DRd vs 11.4 months in Rd (HR 0.19; 95% CI, 0.06-0.55; P=0.0007), and ≥CR % was significantly higher with DRd vs Rd (52% vs 9%; P=0.0002). In CASTOR, 23/251 (DVd) and 35/247 (Vd) were ≥75 y, with 100% and 94% having ECOG status ≤1, respectively. With 13.0 months of median follow up, rates of discontinuation due to TEAEs were similar (15% vs 20%). Thrombocytopenia, fatigue, and pneumonia were common grade 3/4 TEAEs for DVd (Table). Thirteen (65%) pts reported IRR (10% grade 3/4) and no pts discontinued due to IRR. Median PFS was NR in DVd vs 8.1 months in Vd (HR 0.27; 95% CI, 0.12-0.61; P=0.0007), and significantly higher ≥CR % was observed in DVd vs Vd (25% vs 3%; P=0.0154). Conclusions: The safety and efficacy profiles in elderly pts were generally comparable with the overall population in each study. Clinical trial information: NCT02136134 and NCT02076009. [Table: see text]
TCT-843 Evaluation of safety and efficacy of left and right heart catheterization from transradial and antecubital access in patients on anticoagulation
Authors: Felipe Marques, Gustavo Neves de Araújo, Guilherme Pinheiro Machado, None Sandro Goncalves, Luiz Carlos Bergoli, Marco Wainstein, Rodrigo Wainstein
Journal: Journal of the American College of Cardiology (2018)
P05.83 Tumor Treating Fields and radiosurgery for supra- and/or infratentorial brain metastases (1–10) from NSCLC in the phase 3 METIS study
Authors: O Bähr, M Mehta, V Gondi, M Ahluwalia, P Brown
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising low intensity alternating electric fields. TTFields has demonstrated efficacy in non-small cell lung cancer (NSCLC) in in vitro and in vivo models, and in a phase I/II clinical study. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. This prospective, multicenter study [NCT02831959] investigated the efficacy, safety and neurocognitive outcomes of TTFields in NSCLC patients with brain metastases (BMs). NSCLC patients (N=270) with 1-10 BMs are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, > 18 hours/day) within 7 days of SRS or supportive care. The TTFields portable device delivers TTFields to the brain using 4 transducer arrays and allows normal daily activities. Patients receive the best standard-of-care for their systemic disease. Patients are followed every two months until second intracranial progression. Patients in the control arm could cross over to TTFields at the time of second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial BMs from NSCLC amenable to SRS; KPS ≥70; and optimal therapy for extracranial disease. Prior WBRT or surgical resection of metastases, a single resectable lesion or recurrent BMs were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 BMs; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression.The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57. N/A TiP.