tbuckley/cabot-search huggingface dataset:
Proton pump inhibitor (PPI) exposure and risk of pancreatic cancer (PC): Meta-analysis.
Authors: Nasser Mubarak Al Khushaym, Abdulaali Almutairi, Saad Fallatah, Abdulhamid Althagafi, Mok Oh, Ali McBride, Hani M. Babiker, Ivo Abraham
Journal: Journal of Clinical Oncology (2019)

e15755 Background: PPIs are widely used in the treatment of various acid related disorders. Observational studies have raised concern about an association of PPI use and PC but findings have been inconsistent. This meta-analysis aimed to estimate from published studies the pooled PC risk among subjects exposed and not exposed to PPIs. Methods: We searched PubMed, EMBASE, Scopus, Cochrane Library and clinicaltrials.gov to identify relevant studies on the association of PPI exposure and PC risk. Three reviewers independently screened search results for eligibility and extracted data from retained studies. Our primary analysis quantified PC risk among subjects exposed vs not exposed to PPI, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) as estimated in a random effect model. We performed similar secondary analyses in selected subgroups. Results: Of the 2683 reports yielded by the search 1 randomized trial, 2 cohort, and 9 case-control studies with 1,093,766 subjects (123,214 cases; 970,552 controls) were retained. Our main analysis (exposed vs non exposed) revealed a significant overall association between PPI exposure and PC risk (OR 1.77, 95%CI 1.14-2.74). Secondary analyses showed higher risk estimates from high quality (NOS &gt; 7) studies (OR 2.04, 95%CI 1.03-4.02), observational studies (aOR, 1.70 95%CI 1.08-2.68), and studies with PPI use and PC risk as main outcome (aOR 2.01, 95%CI 1.06-3.83). Subgroup analyses by comorbidities showed an association with diabetes (aOR 1.98, 95%CI 1.02-3.82) but not pancreatitis (aOR 1.77, 95%CI 0.93-3.35). PC risk was not associated with duration of PPI use longer 1 (aOR 1.36 95%CI 0.81-2.28 and &gt; 3 yrs (aOR 1.21 95%CI 0.73-2.02). In addition to the overall PPI class effect in the primary analysis, rabeprazole was singularly associated with PC risk (aOR 5.40 95%CI 1.98-14.70). Conclusions: Pooled risk estimates suggest that the class of PPIs is associated with a general 1.77 fold increase in PC risk, independent of duration of PPI exposure. Diabetic patients are at a significant incremental risk over the base risk.
Risk of mortality varies by type of fat consumed in a longitudinal cohort of head and neck cancer patients.
Authors: Hania M. Taha, Laura S. Rozek, Yi Tang Chen, Alexander N Slade, Gregory T. Wolf, Anna Arthur
Journal: Journal of Clinical Oncology (2019)

6056 Background: Dietary interventions have promise for improving cancer outcomes, but remain an understudied area of cancer care. The relationship between head and neck squamous cell carcinoma (HNSCC) mortality and dietary fat intake has not yet been examined. The objective of this study was to determine how pre- and post-treatment intake of various types of fat are associated with disease-specific and all-cause mortality in adults diagnosed with HNSCC. Methods: Our sample included 472 newly diagnosed HNSCC patients recruited into the University of Michigan Head and Neck Specialized Program of Research Excellence (HN-SPORE) between 2008 and 2012. Participants completed pre-treatment and post-treatment Food Frequency Questionnaires (FFQs) and health surveys. Multivariable Cox Proportional Hazards models were used to test the associations between both the type and quantity of fat intake (categorized into tertiles: low, medium and high intake) and time to mortality, after adjusting for relevant covariates. Fat types included animal, vegetable, medium-chain-fatty-acids (MCFA), long-chain-fatty-acids (LCFA), unsaturated, saturated, and trans. Results: During the study period, there were 144 total deaths and 97 cancer-specific deaths. In considering pre-treatment dietary intake, compared to low intake levels of LCFA, high intake was associated with a reduced risk of all-cause mortality (HR: 0.57; 95% CI: 0.34–0.94). High intakes of unsaturated-fats were associated with a reduced risk of HNSCC-specific mortality compared to low intake (HR 0.52; 95% CI: 0.29–0.93). Considering post-treatment dietary variables, medium (HR: 0.21; 95% CI: 0.08–0.49) and high (HR: 0.41; 95% CI: 0.21–0.78) total fat intakes were associated with reduced risk of all-cause mortality compared to low intake. Medium (HR: 0.25; 95% CI: 0.08–0.67) and high (HR: 0.26; 95% CI: 0.09–0.67) total fat intakes were associated with reduced risk of HNSCC-specific mortality compared to low intake. Conclusions: Our data suggest that HNSCC prognosis may vary depending on both the type and quantity of fats consumed, specifically total fat and long chain fatty acids. Clinical intervention trials are needed to further examine this hypothesis.
Case 36-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Jules L. Dienstag, Marlene R. Eckstein, Robert T. McCluskey
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 24-year-old man was admitted to the hospital because of accelerated hypertension.He was well until nine months earlier, when he was seen at another hospital because of malaise and arthralgia; no diagnosis was established. Six months before admission the malaise worsened, and anorexia and abdominal cramps developed. He returned to the same hospital, where a test for hepatitis B surface antigen was positive. One month later he began to experience paresthesia in both feet that gradually migrated up the left calf and was accompanied by dragging of the right foot. Abdominal pain and nausea developed, and . . .
TrkA neurotrophin receptor and PI3K-Akt signaling involvement in cranial irradiation-induced memory deficit.
Authors: Shengjun Ji, Ming Yang, Jinming Yu
Journal: Journal of Clinical Oncology (2019)

e14679 Background: This study aimed to investigate the role of neurotrophin receptor TrkA in cranial radiation-induced memory decline. Methods: Single dose of 10Gy 4MeV electron beam whole brain irradiation (WBI) was given to young male Sprague-Dawley rats (50–60g, day 21). 3 months after WBI, western blot was performed to detect protein level of TrkA and its downstream signaling molecules. The Morris water maze test was performed to evaluate the consequence of WBI on hippocampus-dependent memory formation. Immunohistochemistry was performed to evaluate the consequence of WBI on neurogenesis. For overexpression of TrkA, Adeno-associated virus were injected at the rate of 0.2μl/min (n = 15-20 per group). After that, Morris water maze test was performed again. Results: In Morris water maze test, WBI lead to notable memory deficit, the irradiation rats spent longer latency time than control rats (p &lt; 0.05). In the spatial probe trial, the irradiation rats spent less time in the target quadrant than control rats (p &lt; 0.05). Immunohistochemistry showed that cranial irradiation inhibited proliferation and neurogenesis in hippocampus. The protein level of TrkA expression decreased significantly at 3 months after irradiation compared with control group. Phosphorylation of PI3k, AKT, ERK1/2, CREB were also observed to be significantly inhibited (all p &lt; 0.05). Next, we explored the irradiation-induced apoptotic signal transduction. The increased expression of JNK, caspase-3/9 and reduced expression of BCl2 confirm the irradiation induced apoptosis. After Adeno-associated virus injection, AAV-overexpression TrkA rats showed less escape latency time (p &lt; 0.05) and spent more time (p &lt; 0.05) in the target quadrant than AAV-irradiation rats, but still more escape latency time (p &lt; 0.05) and spent less time (p &lt; 0.05) in the target quadrant than AAV-control rats. Additionally, immunofluorescence staining showed AAV-overexpression-TrkA also rescued radiation-induced neurogenesis impairment Conclusions: TrkA may play a critical role in radiation-induced memory deficit, which indicate the data may have important therapeutic implications.
The relationship between obesity and immunotherapy: It's complicated.
Authors: Douglas MacArthur Donnelly, Shirin Bajaj, Judy Zhong, Jeffrey S. Weber, Anna C. Pavlick, Arjun Vasant Balar, Miles Hsu, Iman Osman
Journal: Journal of Clinical Oncology (2019)

9562 Background: Obesity is a poor prognostic factor in primary melanoma, and preclinical data has linked it to an immunosuppressive phenotype. Paradoxically, recent reports suggest that obesity may confer a survival benefit in patients with metastatic melanoma (MM) who received immune checkpoint inhibition (ICI). Herein we tested the hypothesis that the relationship between body mass index (BMI) and response to ICI depends on type of ICI and tumor type. Methods: We examined 2 cohorts (MM patients [n = 423] and metastatic bladder cancer [MBC] patients [n = 42]). We tested the associations between BMI and PFS, stratified by first vs. second or greater-line of treatment and treatment type (anti-CTLA4, anti-PD1, combination therapy), adjusting for age, gender, stage, LDH level, ECOG status, number of metastatic sites, and BMI classification changes in the MM cohort. Results: We observed a moderate but insignificant association between being overweight (BMI 25.0-29.9 kg/m 2 ) or obese (BMI &gt; 30kg/m 2 ) and better PFS in patients who received first line ICI therapy (aHR 0·77 [95% CI 0·50-1·20]), and an association with worse PFS in patients who received non-first line ICI therapy (aHR 1.31 [0·74-2.33], P interaction = 0.11). Overweight and obese patients receiving combination ICI had a statistically significant survival benefit (aHR 0.27 [0·10-0.70]), p = 0.007), whereas patients receiving the other treatment types showed heterogeneous trends (P interaction = .005). In the MBC cohort, being overweight conferred the greatest PFS benefit, followed by normal BMI, with obesity being associated with the worst PFS (p = 0.035). Conclusions: Stratifying by clinical features including treatment type, treatment line, and tumor type demonstrated vastly different results and reversal of trends, which underpins the complexity of the relationship between BMI and response to ICI. The lack of consistency amongst our data and published reports highlights the need for a thorough investigation, on a significantly larger scale, to truly elucidate obesity's impact on clinical outcomes in cancer. The scientific community must consider this complexity as well as the known detrimental health effects of obesity when counseling patients.
Clinical outcomes of NSCLC patients with acquired <i>RET</i> rearrangement after resistance to osimertinib.
Authors: Chang Lu, Jia-Tao Cheng, Jin Kang, Yi-Hui Yao, Xiang-Meng Li, Xuchao Zhang, Qing Zhou, Hai-Yan Tu, Yi-Long Wu, Jin-Ji Yang
Journal: Journal of Clinical Oncology (2019)

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1 st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1 st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]
Case 15-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Martin A. Samuels, James F. Southern
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 26-year-old woman was admitted to the hospital because of a question of dilated cardiomyopathy and a stroke.She was well until six days earlier, when she went out with friends. On the following morning the patient experienced a severe headache and nausea and remained home during the next two days. A friend noticed that she felt "warm." Three days before admission the patient was found lying on her bathroom floor, confused. It was observed that food and drink brought by her friends two days earlier were untouched. Ambulance personnel found a faint pulse at a rate . . .
Plasma biomarkers to predict pembrolizumab response in HCC patients.
Authors: Lynn G. Feun, Ying-Ying Li, Chunjing Wu, Medhi Wangpaichitr, Patricia Denise Jones, Deukwoo Kwon, Peter Joel Hosein, Niramol Savaraj
Journal: Journal of Clinical Oncology (2019)

e14043 Background: Pembrolizumab (PEM) has been approved as second line therapy for the treatment of hepatocellular carcinoma (HCC). We conducted a single institution investigator-initiated clinical/biomarkers trial to assess potential biomarkers to predict response in unresectable HCC patients (pts) receiving PEM. Methods: PEM was administered at 200mg iv. every 3 weeks for advanced HCC pts who progressed on, were intolerant of, or refused sorafenib. The circulating levels of cytokines/chemokines included IL-1β, IL-6, IL-8, IL-12, IL-18, IFN-γ, TGF-β, IL-10, CXCL9, CCL4, CCL5, as well as PD-1, PD-L1, PD-L2 were measured by ELISA at baselines and at day 60-90. PD-L1 expression in tumor was also assessed by histopathological staining. Results: 29 pts have been treated and 28 were evaluated for response. One pt had complete response, 8 had partial response and 4 had stable disease. Among all the biomarkers tested, only TGF-β at baseline predict response. The mean of plasma TGF-β in responders were 141.9pg/ml vs. 1071.8pg/ml in nonresponders. The cut-off values was determined based on the near medians. The plasma concentration of TGF-β of ≥200pg/ml was an index for nonresponder (P = 0.003). Kaplan-Meier analysis showed that the median overall survival (OS) and progression-free survival (PFS) in pts with TGF-β ≥200pg/ml were 7 months and 2 months, respectively, while in pts with TGF-β &lt; 200 pg/ml, the OS and PFS were over 25 months(P = 0.005 and P = 0.008, respectively). Plasma IFN-γ or IL-10 levels positively correlated with plasma PD-1/PD-L-1 (P &lt; 0.05). Since tumor PD-L1 expression is upregulated by IFN-γ, and IL-10, and interacts with PD-1 to suppress T cell, to confirm these relationships, the linear regression was used to analyze the data. Plasma IFN-γ or IL-10 levels positively correlated with plasma PD-1 and PD-L1 levels ( P &lt; 0.05). Nine of these 24 patients had tumor available for PD-L1 scoring (PD-L1-positive:3 pts and PD-L1-negative:6pts). Similar to plasma PD-L1 concentration, pts with positive tumor PD-L1 had high levels of plasma IFN-γ or IL-10 ( P &lt; 0.05). Conclusions: Our study confirmed that PEM is active in HCC and TGF-β is a predictive markers for tumor response, PFS, and OS. Support by grant from Merck
CANOPY-A: A phase III study of canakinumab as adjuvant therapy in patients with surgically resected non-small cell lung cancer (NSCLC).
Authors: Edward B. Garon, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Pedro De Marchi, Yasushi Goto, Shun Lu, Luis G. Paz-Ares, David R. Spigel, Michael Thomas, Bijoyesh Mookerjee, Pilar Cazorla Arratia, Jason Baum, Yi-Yang Yvonne Lau, Zewen Zhu, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2019)

TPS8570 Background: Overexpression of interleukin (IL)-1β has been described in solid tumors, including lung. IL-1β can promote angiogenesis, tumor invasiveness, and induce tumor-associated immunosuppression through myeloid-derived suppressor cell (MDSC) accumulation in tumors. Pre-clinical data has shown that IL-1β inhibition stably reduces tumor growth, by limiting inflammation and inducing the maturation of MDSCs into M1 macrophages. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Recently, it was found that canakinumab was associated with a significant and dose-dependent reduction in incidence and mortality from lung cancer based on CANTOS study. Methods: CANOPY-A is a phase III, randomized, double-blind, placebo-controlled study designed to evaluate efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected NSCLC. This trial will enroll adult patients, with completely resected (R0) AJCC/UICC v.8 stages II−IIIA and IIIB (T &gt;5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or neoadjuvant radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg Q3W, s.c) or placebo (Q3W, s.c.) for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region. The primary objective is disease-free survival, per investigator assessment. Secondary objectives include overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Enrollment is ongoing. Clinical trial information: NCT03447769.
The depth of response was associated with the progression-free survival in advanced non-small cell lung cancer patients treated with EGFR-TKI.
Authors: Yutao Liu, Kai Zhang, Chengcheng Li, Xingsheng Hu, Jun Jiang, Xuezhi Hao, Yan Wang, Junling Li, Puyuan Xing, Sheng Yang, Xin Zhang, Guoqiang Wang, Shangli Cai, Yuankai Shi
Journal: Journal of Clinical Oncology (2019)

e20509 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate the new therapeutic strategies in cancer, however, RECIST fails to differentiate the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as maximum percent change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or 19del) treated with EGFR-TKI from August 2014 to July 2017 in two sites were retrospetively collected for analysis. Patients were divided into four groups by maximal tumor shrinkage (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS by DepOR and the hazard ratio (HR) was determined through univariable and multivariable Cox regression models. Results: In total, 265 patients were included for analysis. The number for Group Q1-Q4 was 91, 73, 65 and 36, respectively. The greater DepOR was significantly associated with a longer PFS (Log-rank P for trend &lt; 0.0001). The DepOR vs PFS analyses HR were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3 and 0.33 (0.22-0.50) for Q4 compared with Q1. In the multivariable cox regression model, abnormal LDH, brain metastasis and male were also found to be associated with poorer PFS (P &lt; 0.05). Conclusions: Greater DepOR was significantly associated with a longer PFS in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to more efficiently evaluate the response of targeted therapy.
HIV associated cancers.
Authors: Prabhjot Singh Bedi, Manoj P. Rai, Fawzi Abu Rous, Rohanlal Vishwanth, Nishraj Basnet, Calvin Abro, Ikponmwosa Enofe, Shilpa Kavuturu, Supratik Rayamajhi
Journal: Journal of Clinical Oncology (2019)

e18254 Background: The incidence or the prevalence of AIDS-defining cancers has reduced drastically (70% or more in the United States) since the introduction of three-drug antiretroviral therapy (ART) in the mid-1990s. However, the data from the inpatient sample is lacking. Methods: This is a retrospective analysis using data from the 2014 National Inpatient Sample database. We identified patients with either primary or secondary diagnosis of human immunodeficiency virus (HIV). Then we identified patients with various cancers including AIDS-defining cancers. Afterward, we ran logistic regression to check the degree of association between the diagnosis of each cancer with the diagnosis of HIV during the identified hospitalizations. We also assessed the prevalence of each of the cancer among the identified HIV patients, as well as the mortality in this cohort. Results: A total of 115955 hospitalizations with a diagnosis of HIV were identified. Among them, there were 6985 hospitalizations with Non-Hodgkin lymphoma, 2230 with rectal and anal cancer, 1170 with Kaposi sarcoma, 870 with head and neck cancer, 865 with skin cancer, 840 with cervical cancer. Logistic regression showed odds ratio (OR) of 1632.857 (95% CI 1168 - 2284, p &lt; 0.01) for Kaposi sarcoma, 9.13 (95% CI 5.7-14.5, p-value &lt; 0.01) for other male cancer, 8.34 (95% CI 7.68-9.06; p-value &lt; 0.01) for Non-Hodgkin's lymphoma, 6.65 (95% CI was 5.5-8, p-value &lt; 0.01) for Hodgkin's lymphoma, 5.04 (95% CI 4.5-5.6 p &lt; 0.01) for rectal and anal cancer, 2.33 (95% CI 1.9-2.8, p &lt; 0.01) for cervical cancer. Mortality was statistically significant with liver cancer, lung cancer, brain cancer, Hodgkin lymphoma, and Kaposi sarcoma. Conclusions: The prevalence of Kaposi sarcoma, Non-Hodgkin lymphoma, and cervical cancer are found to be high among hospitalized patients with HIV most likely because of nonadherence to their HIV medications. Future studies to check their correlation of these cancers with disease control is required. It is interesting to note that the prevalence of rectal and anal cancer, head and neck cancer, and skin cancer is high in this cohort.