tbuckley/cabot-search huggingface dataset:
Association of CDH1 mutation with prognosis in gastric adenocarcinoma.
Authors: Xiangyang Yu, Shimin Yang, Rong Du, Jingbo Zhang, Nan Fang, Junpo Wang, Yu Tang, Jianwei Wang, Qixi Wu
Journal: Journal of Clinical Oncology (2019)

e15514 Background: Stomach cancer is a major cause of cancer death in East Asia. The purpose of this study was to find a predictive marker to estimate the prognosis of stomach cancer. Methods: In this study, a total of 34 gastric cancer patients receiving therapy in Tianjin Nankai Hospital were enrolled. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue sections, including carcinoma and pericarcinous tissues. Targeted regions of 549 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina Next-Seq 500 platform. Results: 25/34 patients had tumor metastasis. 135 non-silent mutations in 62 genes were detected in 27 tumor samples, while 7 patients’ samples had no mutation detected. CDH1, BRCA2 and SMAD4 gene mutations only occurred among metastasis patients. CDH1, BRCA2 and KRAS gene mutations are associated with a lower overall survival rate. Among them, 5 patients had a CDH1 mutation, including one splicing mutation, three frameshift mutations, one non-frameshift mutation and two non-synonymous mutations. All five patients had tumor metastasis, with the survival time less than 17 months, compared with all patients’ average overall survival of 22 month. Conclusions: Previous studies showed that mutation in CDH1 is linked to gastric cancer (GC) susceptibility and tumor invasion. Our results indicated that the mutation of CDH1 was also associated with the prognosis of gastric adenocarcinoma (P &lt; .01) and was an independent factor (P &lt; .05).
Case 19-1984
Authors: F. Griffith Pearson, Eugene J. Mark
Journal: New England Journal of Medicine (1984)

Presentation of CaseFirst admission. A 50-year-old woman was admitted to the hospital because of unresolved pneumonia.She was well until two years earlier, when right-sided pneumonia developed and resolved slowly on treatment. Three months before entry fever, cough, and sputum production recurred, and she entered another hospital. An antibiotic was administered, with improvement. Her symptoms recurred on two occasions, and she was readmitted to the same hospital for treatment each time. X-ray films of the chest showed atelectasis of the right middle lobe (Fig. 1). She began to experience exertional dyspnea and vague discomfort in the right side . . .
A phase II Salvage Trial of AR Inhibition with ADT and Apalutamide with Radiation therapy followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (STARTAR).
Authors: Tian Zhang, Bridget F. Koontz, Scott T. Tagawa, Himanshu Nagar, Rhonda L. Bitting, Bart Frizzell, Julia Rasmussen, Rhonda Wilder, Monika Anand, Carolyn Winters, Colleen Riggan, Aileen Lee, Patrick Healy, Yuan Wu, Megan Ann McNamara, Michael Roger Harrison, Daniel J. George, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2019)

TPS5097 Background: Androgen deprivation combined with salvage external beam radiation therapy (RT) have improved survival for patients (pts) with non-metastatic hormone naïve PC and PSA recurrence after radical prostatectomy (RP). Our recent STREAM trial showed addition of enzalutamide to RT and ADT had a 3-year progression free survival (PFS) of 53%. Adding effective PC treatments in this setting may further improve 3-year PFS. Methods: STARTAR is an investigator-initiated phase 2 trial for salvage treatment of biochemically recurrent PC following prostatectomy. Key inclusion criteria include histologic prostate adenocarcinoma, either Gleason 7 with T3/positive margin/1-4 positive lymph nodes or Gleason 8-10 disease, PSA relapse within 4 years of prostatectomy (minimum PSA 0.2 ng/mL to maximum PSA 4 ng/mL). Treatment involves ADT with apalutamide for 9 months, continue with with prostate bed +/- nodal RT at month 3, followed by 6 cycles of docetaxel 75mg/m2 IV every 3 weeks for 6 cycles. The primary endpoint of the study is 3-year PFS. With a one-sided alpha of 0.05 to improve 3-year PFS from 50% to 75%, we will have 92% power by enrolling 42 pts (including 10% dropout rate) based on the binomial test. Key secondary endpoints include 1, 2, and 3-year PSA recurrence rates with testosterone recovery, PSA PFS, PSA nadir, time to testosterone recovery, and safety of combination therapy. Quality of life will be assessed by EPIC questionnaire. As of February 2019, we have enrolled and treated 12 pts in this PCCTC trial. Accrual to the STARTAR trial is ongoing (NCT03311555). Clinical trial information: NCT03311555.
Disparities in pretest genetic counseling among a population-based sample of young breast cancer patients.
Authors: Sonya Reid-Lawrence, Tuya Pal, Ingrid A. Mayer, Xiao-Ou Shu, Ann Tezak, Anne Weidner, Deborah Cragun, Susan Thomas Vadaparampil, Fei Ye, Run Fan
Journal: Journal of Clinical Oncology (2019)

1579 Background: Per national practice guidelines, pre-test genetic counseling (GC) through a board-certified or credentialed genetics health professional (GHP) is recommended when testing for hereditary cancer. We sought to compare differences in rates of pre-test GC among young breast cancer (BC) patients tested with or without GHP involvement across three racial groups (Black, Hispanic and non-Hispanic white (NHW)). Methods: A population-based sample of Black, Hispanic and NHW women diagnosed with invasive BC ≤ age 50 from 2009 to 2012 were recruited through the Florida State Cancer Registry. Participants were asked to complete a baseline questionnaire and release medical records for verification of clinical information and genetic testing. We compared the rates of pre-test GC across racial groups in women tested with or without GHP involvement using Analysis of Variance. Multivariate logistic regression analysis was also conducted to adjust for potential confounders. Results: Of 1618 participants, 828 had genetic testing based on medical records and/or self-reported on their questionnaire. There were 170 (20.5%) with GHP involvement (either through consultation and/or test ordering) and the remaining 658 women (79.5%) had no documentation of GHP involvement. Among patients tested without GHP involvement, rates of pre-test GC were significantly lower among Black women (34.8%) compared to Hispanics (80%) and NHW (78.7%) (p &lt; 0.001). In contrast, among those with GHP involvement, rates of pre-test GC were similar among Black (89.7%), Hispanic (81.1%) and NHW (84.6%) (p = 0.89). Conclusions: Our results suggest that among young breast cancer patients tested for hereditary cancer without GHP involvement, Blacks were significantly less likely to receive pre-test GC, compared to the other two groups. In contrast, rates of pre-test GC among those with GHP involvement were similar across all groups. These results suggest a disparity in receipt of pre-test GC (which is standard of care per national guidelines) among Blacks tested without GHP involvement. These findings are concerning given the need to offer guideline-adherent care to all patients receiving hereditary cancer testing.
Exploring the emerging role of the microbiome in cancer immunotherapy
Authors: Jessica Fessler, Vyara Matson, Thomas F. Gajewski
Journal: Journal for ImmunoTherapy of Cancer (2019)

The activity of the commensal microbiota significantly impacts human health and has been linked to the development of many diseases, including cancer. Gnotobiotic animal models have shown that the microbiota has many effects on host physiology, including on the development and regulation of immune responses. More recently, evidence has indicated that the microbiota can more specifically influence the outcome of cancer immunotherapy. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes have shown promise in mouse studies. Ongoing endeavors are translating these pre-clinical findings to early stage clinical testing. In this review we summarize 1) basic methodologies and considerations for studies of host-microbiota interactions; 2) experimental evidence towards a causal link between gut microbiota composition and immunotherapeutic efficacy; 3) possible mechanisms governing the microbiota-mediated impact on immunotherapy efficacy. Moving forward, there is need for a deeper understanding of the underlying biological mechanisms that link specific bacterial strains to host immunity. Integrating microbiome effects with other tumor and host factors regulating immunotherapy responsiveness versus resistance could facilitate optimization of therapeutic outcomes.
Case 45-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Kenneth L. Tyler, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 67-year-old woman was admitted to the hospital because of confusion and a left homonymous hemianopia.There was a seven-year history of chronic lymphocytic leukemia. Twelve months before entry an x-ray film of the chest showed a nodular density in the right middle lobe that had increased slightly in size in comparison with a film obtained three months earlier. A computed tomographic (CT) scan of the thorax revealed nodular densities in the middle lobe and posterior portion of the right lower lobe; small paraaortic lymph nodes were present, and there was a probable enlarged lymph node inferior . . .
Factors associated with receipt and overall survival of concurrent chemoradiotherapy versus single modality therapy in unresectable stage III NSCLC.
Authors: Jorge E. Gomez, Kellie Ryan, Priyanka J. Bobbili, Akanksha Dua, Maral DerSarkissian, Mei Sheng Duh
Journal: Journal of Clinical Oncology (2019)

e18191 Background: While concurrent chemoradiotherapy (cCRT) is standard of care for patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC), some pts receive single modality therapy. This study identified predictors of therapy and differences in overall survival (OS) in a Medicare population. Methods: This retrospective study used Surveillance, Epidemiology and End Results -Medicare data (2009-2014). Stage III NSCLC pts aged ≥65 yrs, with ≥1 claim for systemic therapy or radiotherapy (RT) within 90 days of diagnosis were included. cCRT pts had overlapping claims for chemotherapy and RT ≤90 days from start of therapy; remaining pts were grouped by first therapy received. Sequential CRT patients and those with surgical resection of tumor were excluded from this analysis. Logistic regression was used to analyze predictors of cCRT. Multivariable Cox proportional hazards models were used to compare OS between therapies. Results: Of 4,544 pts identified, 51% received cCRT, 21% systemic therapy, and 27% RT. Across groups, cCRT patients were likely younger (p &lt; 0.001), White (p &lt; 0.001), male (p = 0.015), and with a good predicted performance status (PS) (p &lt; 0.001). After adjustment, several variables were predictive of receiving cCRT (Table). Median OS was 14.7 months (mo) for cCRT vs. 10.9 mo for systemic therapy (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.24-1.49, p &lt; 0.001) vs. 7.8 mo for RT (adjusted HR: 1.55, 95% CI: 1.42-1.69, p &lt; 0.001). Conclusions: Only 51% of pts received cCRT. Age, race, stage, PS and comorbidity index were predictive of cCRT. Given the survival benefit, physicians should be encouraged to pursue cCRT in all eligible pts. Further efforts to develop less morbid therapies are critical in this population. [Table: see text]
Exploring sex differences in small cell lung cancer: Is this a hormonal issue?
Authors: Narjust Duma, Thanh P. Ho, Urshila Durani, Shealeigh Funni, Jonathan Inselman, Harshita Paripati, Alex A. Adjei, Julian R. Molina, Aaron Scott Mansfield
Journal: Journal of Clinical Oncology (2019)

e20077 Background: Small cell lung cancer (SCLC) accounts for about 10% to 15% of lung cancers among women and men. Though heavily associated with smoking, its incidence in women is rapidly increasing despite a decline in cigarette exposure. Given the changing demographics of SCLC and hormonal factors associated with other forms of lung cancer, we studied differences between sexes in SCLC. Methods: Utilizing the National Cancer Database, we identified all incident SCLC cases from 2004 to 2014. Patients were classified as limited stage (LS) or extensive stage (ES). Women were stratified by menopausal status (≥55 years = postmenopausal). Kaplan-Meier method and Cox regression were used for overall survival (OS) and multivariable analysis. Results: 161,978 patients were identified. No significant sociodemographic differences were observed between sexes. The majority of patients were non-Hispanic whites (89.1%), followed by non-Hispanic blacks (7.5%). Men were more likely to be diagnosed with ES disease than women (63% vs. 56%). Both sexes initiated treatment within a similar time frame from diagnosis (chemotherapy, median: 18 days, IQR 8-32). Women had better median OS compared to men in both LS (15.2 vs. 12.7 months, HR: 0.85, 95% CI 0.83-0.86, p &lt; 0.0001) and ES (6.4 vs. 5.7 months, HR: 0.88, 95% CI 0.87-0.90, p &lt; 0.0001). No racial or ethnic disparities in OS were observed, overall and when examined within sex and disease stage groups. Differences between sexes in OS were also observed when comparing patients within the same racial/ethnic group (women having better OS). When divided by menopausal status, postmenopausal women with LS and ES had worse OS than premenopausal women (14.7 vs. 22 months, HR: 1.50, 95% CI 1.44-1.56; 6.1 vs. 9.8 months, HR: 1.41, 95% CI: 1.37-1.46, respectively). We also observed worse OS in older men when divided by age ( &lt; 55 years and ≥55 years). In multivariable analysis, older age, postmenopausal status, and Medicaid as primary insurance were associated with worse OS for both LS and ES. Conclusions: In this large cohort, women with SCLC had better OS compared to men. Post-menopausal women had worse OS compared to pre-menopausal women. Since older men had a similar trend of worse survival compared to younger men, age might exert a more significant influence on survival than hormonal status in SCLC. Further studies with data on sexual hormone levels are necessary to better understand their role in women with SCLC.
THU0726-HPR THE COMPARISON OF ARTERIAL STIFFNESS, FUNCTIONAL EXERCISE CAPACITY AND PHYSICAL ACTIVITY IN SYSTEMIC SCLEROSIS AND HEALTHY INDIVIDUALS
Authors: Aylin Tanriverdi, Buse Ozcan Kahraman, Serap Acar, Nazenin Hande Sezgin, Sema Savci, Aydan Koken Avsar, Ebru Ozpelit, Ahmet Merih Birlik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic sclerosis (SSc) is characterized by abnormal production of fibrotic tissue in the skin and internal organs. SSc has a effect on large and conduit arteries damage as well as microvascular damage (1). It is known that sedentary lifestyle may contribute to vascular dysfunction (2). Therefore, it is important to evaluate arterial stiffness, exercise capacity and physical activity in people with SSc. <h3>Objectives:</h3> The aim of this study is to compare arterial stiffness, functional exercise capacity and physical activity in SSc and healthy individuals. <h3>Methods:</h3> Fifteen SSc (53 years) and 15 healthy (48 years) women were included in this study. Arterial stiffness was evaluated with pulse wave velocity that was obtained by measuring the carotid-to-radial pulse wave transit time. Functional exercise capacity was assessed by 6-minute walk test (6MWT). Physical activity was questioned International Physical Activity Questionnaire (IPAQ)-short form. The differences between the groups were analyzed with Mann-Whitney U test. <h3>Results:</h3> Age, weight, height and body mass index were similar in the groups (p&gt;0.05). There was significant difference in pulse wave velocity and pulse wave transit time between the two groups (p&lt;0.05). The 6MWT distance and IPAQ score of the group with SSc were significantly lower than the healthy group (p&lt;0.05). <h3>Conclusion:</h3> This study demonstrates that women with SSc have increased arterial stiffness, decreased functional exercise capacity and physical activity. Exercise training is an important part of the comprehensive care of people with SSc. People with SSc should be included in an exercise training program to reduce arterial stiffness, increase exercise capacity and physical activity. <h3>References:</h3> [1] Cypiene A, Laucevicius A, Venalis A, Dadoniene J, Ryliskyte L, Petrulioniene Z, Kovaite M, Gintautas J. The impact of systemic sclerosis on arterial wall stiffness parameters and endothelial function. Clin Rheumatol. 2008 Dec;27(12):1517-22. [2] Laufs U, Wassmann S, Czech T, Münzel T, Eisenhauer M, Böhm M, Nickenig G. Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis. Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):809-14. <h3>Disclosure of Interests:</h3> None declared
The phase I clinical study of CART targeting BCMA with humanized alpaca-derived single-domain antibody as antigen recognition domain.
Authors: Lu Han, Quanli Gao, Keshu Zhou, Jian Zhou, Baijun Fang, Jishuai Zhang, Hongjian Li, Yongping Song
Journal: Journal of Clinical Oncology (2019)

2535 Background: Several phase I clinical trials already shown Chimeric antigen receptor T cells (CART) targeting BCMA has the promised effects to treat the relapsed/refractory (RR) multiple myeloma (MM), RRMM. We developed CART cells (CART-BCMA) using one single-domain antibody as recognition domain. The anti-BCMA single-domain antibody was derived from the alpaca, and humanized with the affinity of 1.14nM. The CART-BCMA use the 4-1BB and CD3ζ intracellular regions as T cell activation domain. Methods: A phase I, single arm clinical study was conducted to assess safety and efficacy of CART-BCMA. The enrolled RRMM patients had received average 10 lines of prior treatment, no matter BCMA expression level on plasma cells. Patients were subjected to a lymphodepleting regimen with Cy (300-600 mg/m 2 , d-5, -4) and Flu (30 mg/m 2 , d-5 to d-3) before CART infusion at the dose of 2-10×10 6 CAR + cells/kg. The efficacy was assessed based on the IMWG Criteria, and the toxicity was graded by CTCAE 4.02. Results: As of December 31, 2018, 16 patients were infused with autologous CART-BCMA cells, and had at least 1 month of follow-up. Many patients have M protein in serum, but haven't the high percent of plasma cells in bone marrow, which are difficult to be treated by CART cells because the tumor cells are aggregated, not diffused in bone marrow. 3 patiens were diagnosed with extramedullary diseases, were evaluated as PR at D28 (tumor SPD decreasing &gt;50%). 13 patients haven't extramedullary diseases, at D28, ORR is 84.6% (11/13); At 10 weeks, 7 patients were evaluated, ORR is 100% (sCR/CR 42.8%, VGPR 14.3% , PR 42.8% ); 5 patients reached 16 weeks, 1 relapsed, 4 kept remission. The Pt3 and Pt6 shows the CRS grade 3 or 4, other patients shows the grade 0-2 CRS, the CRS is manageable. Conclusions: Our result demonstrates the promising efficacy compared with other reported results of CART targeting BCMA, and supports further development of this anti-RRMM cellular immunotherapy. Clinical trial information: NCT03661554.
Prognostic Utility of Serum TARC, MDC, IL10, and Soluble CD163 Levels with Positron Emission Tomography (PET) Response-Adapted Therapy for Advanced-Stage Hodgkin Lymphoma (HL): a SWOG S0816 US Intergroup Correlative Study
Authors: Eric D. Hsi, Hongli Li, Andrew B. Nixon, Andrew M Evens, Heiko Schoder, David J. Straus, Nancy L. Bartlett, John William Sweetenham, Paul M. Barr, Michelle A. Fanale, James R. Cook, Brad S Kahl, John P. Leonard, Sonali M. Smith, Michael L. Leblanc, Lisa M. Rimsza, Jonathan W. Friedberg, Oliver W. Press
Journal: Blood (2017)
Influence of timing of goals of care discussion on hospitalization outcomes in metastatic cancer patients.
Authors: Oluwadunni Emiloju, Djeneba Audrey Djibo, Jean G Ford
Journal: Journal of Clinical Oncology (2019)

e18183 Background: Cancer patients often require acute hospitalizations, many of which are unplanned. These hospitalizations have been shown to increase in frequency near the end of life. The American College of Physicians recommends that goals of care (GOC) discussions be initiated early for metastatic cancers. We hypothesize that discussing GOC during hospitalization will help reduce readmissions and improve patient satisfaction, by helping to ensure that patients receive goal-congruent care. We aim to examine the association between the timing of GOC discussion and the patient's length of stay and the time to hospital readmission. Methods: We conducted a retrospective review of medical records of patients with stage IV solid tumors who were hospitalized acutely between August 2017 and July 2018 (N = 241). We assessed demographics, clinical information, timing of GOC discussion, use of palliative care services and hospital readmissions within 90 days. Chi-square tests were used to identify independent associations with having a GOC discussion; and anova was used for continuous variables. We used logistic regression to examine the association with a hospital readmission within 90 days, controlling for potential confounders. Results: The subjects were 26-92 years old and 40.6% were female. Only 43% (n = 106) of patients had a GOC discussion. Age, gender, tumor site, and presenting complaint were not independently associated with having a GOC discussion (p &gt; 0.05). Overall, 34.4% (n = 83) had a palliative care encounter. Having a palliative care consult and being admitted to critical care were independently associated with having a GOC discussion. Early timing of GOC discussion was inversely associated with admission to critical care units (p &lt; 0.05). Length of stay was positively correlated with having a GOC discussion. Thirty-seven percent (n = 91) had unplanned hospital readmission within 90 days. Having any GOC discussion reduced the odds of an unplanned hospital readmission within 90 days by 75% [OR = 0.25, 95% confidence interval (CI) 0.14-0.45]. Conclusions: Among hospitalized patients with stage IV cancer, performing an early GOC discussion is associated with better hospitalization outcomes. It is therefore important to perform GOC discussion early when such patients are acutely hospitalized.