tbuckley/cabot-search huggingface dataset:
Prevalence of HIV infection among cancer patients in a Haitian hospital.
Authors: Joseph Bernard, Lenz Sacha Christyl Pierre, Keddy Moise, Vincent DeGennaro
Journal: Journal of Clinical Oncology (2018)

1575 Background: Malignancies are nowadays among the main conditions affecting HIV-infected patients. The state of immunosuppression puts these patients at high risk of developing cancer in their lifetime. The objectives of this study were to determine the prevalence of HIV infection among cancer patients and compare the overall mortality rate between the HIV-positive and HIV-negative subpopulations. Methods: A two-year retrospective study was conducted in the cancer program of Innovating Health International (IHI). Were included all cancer patients with a known HIV status enrolled from January 1st, 2016 to December 31st, 2017. Date of admission, age, gender, cancer type, cancer stage, antiretroviral therapy status for HIV-infected patients and outcome were the main variables selected for this chart review. HIV infection was tested as a factor associated with mortality. Results: Among the 785 cancer patients selected for this study, 398 (50.7%) had a known HIV status. Thirty (7.5%) of them were HIV-infected, among them 19 women and 11 men. The mean age was 45.9 years [25-69] versus 49.5 years [16-87] for the HIV-negative patients (p = 0.15). There were 11 patients with AIDS-defining cancers (ADC) such as invasive cervical cancer (n = 8) and Non-Hodgkin lymphoma (n = 3). 18 patients had Non-AIDS-defining cancers (NADC) such as head and neck cancers (n = 8), among them 3 oral cancers and 3 ocular cancers, breast cancer (n = 4), penile cancer (n = 2), and one case each of Hodgkin’s lymphoma, lung cancer, ovarian cancer and pancreatic cancer. 1 patient had a carcinoma of unknown primary (CUP). 22 of these 30 patients (73.3%) were already known HIV-infected before their admission and were on antiretroviral therapy. 75% of the staged patients were at stages III or IV of their cancer. The overall mortality rate was 33.3% [95% CI, 17.3% – 52.8%] versus 20.9% [95% CI, 16.9% – 25.4%] for the HIV-negative patients. HIV-infected cancer patients were more likely to die than HIV-negative ones. (Odds ratio = 1.9, p = 0.11). Conclusions: The prevalence of HIV infection among the cancer patients was 7.5% [95% CI, 5.1% - 10.6%], with a predominance of Non-AIDS-defining malignancies. HIV infection was not for this cancer cohort a significant factor associated with mortality.
Using target capture sequencing detect microsatellite instability(MSI), tumor mutational burden(TMB) and <i>POLE/POLD1</i> mutations in colorectal cancer.
Authors: Jing Wang, Dan Liu, Huanwen M. Wu, Yuting Yi, Yan-Fang Guan, Jiucheng Liu, Ling Yang, Xin Yi, Xuefeng Xia, Zhiyong Liang
Journal: Journal of Clinical Oncology (2018)

e15012 Background: Microsatellite instability-High(MSI-H) or mismatch repair protein deficiency (dMMR) is a biomarker to predict immunotherapy response, which is approved by the US Food and Drug Administration in pembrolizumab. Here we describe the comparisons of three methods (IHC\PCR\NGS) in testing MSI or dMMR and also compare the association between MSI, TMB and POLE/POLD1 mutations in colorectal cancer(CRC). Methods: Cases of CRC and matched normal samples were sequenced with 1021 genes panel. TMB was calculated by counting nonsynonymous mutations across a 1Mb coding region. MSI status was analyzed by MSIsensor. TMB-H cutoff was defined more than 20 Muts/Mb referring to the distribution of TMB in MSI-H and MSS pts in cohort 1. Results: 94 samples with MSI status (64 dMMR and 30 pMMR) previously determined by IHC were applied to PCR and NGS. Based on PCR results, the concordance of NGS and IHC was 100% and 91.5%. 8 inconsistent dMMR samples from IHC were proved to be pMMR after review. 1 TMB-H &MSS pts were identified besides 56 TMB-H & MSI-H pts. In 57 TMB-H pts, 32 (56.1%) had POLD1/POLE mutations, and an average of 1.6 mutations was detected per pts. However, none POLD1/POLE mutations were found in 37 TMB-L pts. To verify if POLD1/POLE mutations exist in TMB-H pts specifically, 207 sporadic colorectal cancer samples, including 89 tissues and 118 plasmas, were analyzed. POLD1/POLE mutations appeared in 6 samples: 4 plasma samples (bTMB 20, 29, 57 and 178 Muts/Mb), 2 tissue samples (tTMB 69 and 3 Muts/Mb). The only one found in TMB-L pts was a POLE mutation (p.K2073I, MAF = 4.6%). Conclusions: NGS is a reliable platform to detect MSI status, TMB, and POLD1/POLE mutations. In colorectal cancer, POLD1/POLE mutations have the potential to be an independent biomarker to predict immunotherapy response. Overall, TMB is the biomarker which enables more patients to get benefit from immunotherapy.
Concomitant chemoradiotherapy using docetaxel, cisplatin and 5-FU (TPF) for the patients with advanced squamous cell carcinoma of the head and neck.
Authors: Kiyoto Shiga, Katsunori Katagiri, Daisuke Saitoh, Shin-ichi Oikawa, Aya Ikeda
Journal: Journal of Clinical Oncology (2016)

e17502 Background: Efficacy and usefulness of concomitant chemoradiotherapy (CCRT) using TPF protocol has not yet been clearly distinguished, although it has been effective in the neo-adjuvant setting for head and neck squamous cell carcinoma (SCC) so far. The aim of this study was to determine the safety and efficacy of CCRT using TPF protocol in patients with advanced head and neck SCC and to compare the adverse events among tumor sites. Methods: Patients with previously untreated, histologically proven T4 disease of the temporal bone (TB) and stage IVA disease of the hypopharynx (HP) were eligible for the study. Eleven patients of the TB and 16 patients of the HP were enrolled between December 2001 and August 2010. Treatment consisted of radiotherapy administered once daily to a total dose of 70 Gy, concomitant with 120-hour infusions of 5-FU (600 mg/m2/day), Docetaxel (50 mg/m2, day 2) and Cisplatin (60 mg/m2, day 2) given during first and fifth weeks of radiotherapy. These drug doses were determined from the results of our former phase I study to assess the dose limiting toxicity of this protocol. Median follow-up period was 64 months. Results: Nine patients of the TB and 15 patients of the HP completed this protocol. Bone marrow suppression was the most common adverse event observed through this study. Grade 4 leukopenia and neutropenia were observed in 1 (9%) and 3 (27%) of the patients with TB SCC (TBSCC), 4 (25%) and 8 (50%) of the patients with hypopharyngeal SCC (HPSCC), respectively. Although all patients showed dermatitis and alopecia at any grade, other grade 3 or 4 adverse events in patients with TBSCC were obviously less than in patients with HPSCC. Complete remission was obtained in all patients but one with TBSCC who rejected second course of TPF. The disease-specific and over-all survival rates at 60 months of the patients with TBSCC were 77.8% and 70.7%, respectively, while those with HPSCC were 100% and 67.0%, respectively. Conclusions: Our data suggested that CCRT using TPF protocol was feasible and very effective in patients with advanced stage SCC of the head and neck. However, the adverse events were more frequent in the patients with HPSCC.
The use of proteasome inhibitors among patients with POEMS syndrome.
Authors: Taxiarchis Kourelis, Prashant Kapoor, David Dingli, A. Keith Stewart, Francis Buadi, Morie A. Gertz, Martha Lacy, Shaji Kumar, Wilson I. Gonsalves, Ronald S. Go, John Anthony Lust, Suzanne R. Hayman, Rahma M. Warsame, S.Vincent Rajkumar, Steven R. Zeldenrust, Stephen J. Russell, Lisa Hwa, Robert A. Kyle, Angela Dispenzieri
Journal: Journal of Clinical Oncology (2017)

e19530 Background: Neuropathy is a universal symptom of patients with POEMS syndrome, which makes the use of bortezomib less appealing. However, proteasome inhibitors (PIs) can provide rapid and deep hematologic responses in plasma cell disorders. Because there is very little data regarding the use PIs in POEMS syndrome, we performed a study of patients with POEMS syndrome treated with PIs. Methods: Among the 167 patients with POEMS syndrome seen at our institution between 2001-2016, we identified 12 patients who received a PI. One patient receiving &lt; 1 cycle of bortezomib because of worsening neuropathy was included but was excluded from response analyses. One patient received 2 different PIs at separate points during the disease course and each course was considered separately. Four response categories were considered: hematologic, PET, VEGF and clinical as previously described (Dispenzieri et. al AJH 2015). Results: Among the 12 patients who received 13 courses of therapy, the median age at PI initiation was 59; 8 patients were male. Median number of prior therapies was 1 (0-4) and median time from diagnosis to initiation of PI was 75 months. Excluding steroids, regimens were as follows: bortezomib, n=3; bortezomib and cyclophosphamide, n=4; carfilzomib, n=1; and ixazomib, n=1. With a median follow-up from PI initiation of 18 months, the median duration of treatment was 7 months (1-18). Three patients achieved a hematologic CR. Of 6 patients with an abnormal baseline VEGF, 3 achieved normalization VEGF levels. Of 5 patients with an abnormal baseline PET, 2 achieved normalization of their PET. Two patients had improvement of their neuropathy, with the rest having stable symptoms. Of 9 patients with fluid overload, 8 improved. Only 2 patients stopped therapy due to worsening neuropathy related to PIs. Median PFS and OS from initiation of PI were 50 months and 53 months, respectively. Conclusions: We show that PI use in patients with POEMS syndrome can be safe and effective. Nearly 75% of patients treated with bortezomib had no exacerbation of their neuropathy. Clinical improvement in severe fluid overload symptoms (edema, ascites, pleural effusions) is almost universal, making PI-based therapy an attractive potential option in these patients.
Improving distress screening completion rates: Does virtual robot animation make a difference?
Authors: Tomas Dvorak, Diane Robinson, Emily Ross, Sharlin Milliard, David Metcalf, Julio Hajdenberg
Journal: Journal of Clinical Oncology (2017)

e21672 Background: Distress screening is an important part of cancer patients’ care. Programs accredited by Commission on Cancer must implement distress screening programs, based on improved doctor-patient relationships and clinical outcomes. We are interested in evaluating the use of an anthropomorphic robotic interface to improve survey completion rates and the patient experience. Methods: A validated distress screening survey was scheduled for 74 patients in 2016 in an IRB-exempt survey study. Patients were randomly assigned to fill out the survey on iPAD (N = 33), or on iPAD with a virtual robot animation (“Betty”) introducing the survey (N = 41). Patients were then asked to fill out a validated 10 question Technology Acceptance Model questionnaire (TAM) asking about ease of iPAD use. A five point Likert scale was used. Finally, two yes/no questions were asked: 1) “Were you more interested in filling out the distress screening survey because of the “Betty” animation?”, and 2) “Did the animation make filling out the distress screening survey more enjoyable?” Results: The survey completion rate was 24/33 = 73% for control and 26/41 = 63% for intervention groups (p = 0.86). Forty five patients completed the TAM questionnaire, with completion rate 92% and 88%, respectively. Average iPAD TAM score was 4.3 in the control group and 4.0 in the intervention group (p = 0.12), and none of the 10 questions showed statistically significant difference in ease of use. The last two questions evaluating “Betty” directly were answered by 17/23 and 15/23 patients, respectively. 8/17 felt they were more interested in filling out the distress screening because of “Betty”, and 7/15 felt “Betty” made the distress screening more enjoyable. Conclusions: The presence of “Betty” as part of the survey process did not negatively impact the completion rates. There was no significant difference between the groups in perceived ease of use of the iPAD on which the survey was administered. Approximately half of the patients taking the distress survey with the “Betty” animation felt they were more interested in filling out the survey and the process was more enjoyable. We are currently evaluating whether a true robot may improve completion rates and patient experience.
Malignancy associated SIADH: Characterization and clinical implications.
Authors: Daniel Shepshelovich, Benaya Rozen-Zvi, Rinat Yerushalmi, Anat Gafter-Gvili, Meir Lahav, Hadar Goldvaser
Journal: Journal of Clinical Oncology (2016)

e21622 Background: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common etiology of hyponatremia in cancer patients. SIADH in this population might be directly associated with the malignancy (secretion of vasopressin from tumor cells or presence of either brain or lung metastases), but there are many possible etiologies for SIADH other than the active malignancy including medications, pulmonary infections, pain and nausea. Although SIADH in cancer patients is frequent and clinically significant entity, several issues remain unaddressed in the current literature. The aim of this study was to determine the distribution of etiologies for the SIADH in patients with active malignancies and to characterize patients according to the different etiologies. Methods: This was a single center retrospective study including all patients with active malignancies diagnosed with SIADH between 1.2007 and 1.2013. Two physicians reviewed every patient's medical file for predetermined relevant clinical data. Results: The study cohort included 204 patients. 74.4% of the patients with solid tumors had metastatic disease. Most patients (149 patients, 73%) had malignancy associated SIADH, while 55 patients (27%) had SIADH due to other etiologies. All of the major malignancy types were implicated in SIADH. Patients with breast cancer without lung or brain metastases were significantly less likely to be diagnosed with malignancy associated SIADH compared with other malignancies (Odds Ratio 0.031, 95% CI 0.003-0.25, p < 0.001). Patients with malignancy associated SIADH had lower serum sodium concentrations on short term follow up (p = 0.024) and significantly shorter median survival (58 vs. 910 days, p < 0.001). Short term hyponatremia correction was associated with better survival. Conclusions: SIADH is associated with most malignancy types. Physicians caring for patients with breast cancer without lung or brain involvement diagnosed with SIADH without an obvious etiology should consider obtaining lung and brain imaging to rule out undiagnosed metastatic spread. Patients with malignancy associated SIADH have considerably worse outcomes compared to cancer patient with SIADH due to other etiologies.
Phase Ib/II study of lacnotuzumab (MCS110) combined with spartalizumab (PDR001) in patients (pts) with advanced tumors.
Authors: Aitana Calvo, Heikki Joensuu, Martin Sebastian, Aung Naing, Yung-Jue Bang, Miguel Martin, Desamparados Roda, F. Stephen Hodi, Artur Veloso, Jennifer Mataraza, Guillaume Baneyx, Nelson Guerreiro, Serena Liao, Bertrand Rabault, Marie-Louise Fjaellskog, Andres Cervantes
Journal: Journal of Clinical Oncology (2018)

3014 Background: Tumor-associated macrophages mediate intrinsic/acquired resistance to programmed death-1 (PD-1) inhibitors; these cells can be reduced by inhibiting the colony-stimulating factor-1 (CSF-1)/receptor pathway. Targeting CSF-1 with lacnotuzumab (MCS110), a high-affinity, humanized mAb, combined with spartalizumab (PDR001), a humanized anti-PD-1 mAb, is hypothesized to result in synergistic antitumor activity. Methods: This Phase Ib/II study (NCT02807844) assesses lacnotuzumab with spartalizumab in pts with advanced melanoma, endometrial, pancreatic (PC), or triple-negative breast cancer. During dose escalation, pts received lacnotuzumab at 1 or 3 mg/kg with 100 mg spartalizumab, or 3, 5, 7.5, or 10 mg/kg lacnotuzumab with 300 mg spartalizumab, every 3 weeks. For the Phase Ib part, primary endpoints are safety, tolerability, and recommended Phase II dose; secondary endpoints include antitumor activity and PK. Tumor biopsies are collected before and during treatment. Results: At data cut-off 24 Nov 2017, 50 pts (median age 60 years) were enrolled at 6 combination dose levels. The most common (≥30%) all-grade AEs regardless of study drug relationship were increased aspartate aminotransferase (AST; 32%), nausea (32%), vomiting (32%), asthenia (30%), and fatigue (30%); the most common (≥10%) Grade ≥3 AEs were increased AST (12%), asthenia (10%), and hyponatremia (10%). Frequent AEs suspected as drug-related were periorbital edema* (30%), increased AST (24%), and increased blood creatine phosphokinase (24%), which was the most frequent Grade ≥3 AE suspected as drug-related (6%). By RECIST 1.1, there was 1 partial response (PR); stable disease (SD) was 19% (9/48). By immune-related response criteria, disease control rate (irPR or irSD) was 27% (13/48); of note, 6/13 had PC. Out of 30 pts with PC, 1 pt achieved PR (on study for 346 days) and 2 pts had durable SD (on study for 328 and 319 days, respectively). PK and biomarker studies are ongoing. Conclusions: Lacnotuzumab with spartalizumab was well tolerated overall. Preliminary antitumor activity, notably in the PC cohort, was observed. Ongoing studies are evaluating this combination. *Includes eyelid edema and face edema. Clinical trial information: NCT02807844.
Association between T cell repertoire diversification and both clinical response as well as toxicity following immune checkpoint blockade in metastatic cancer patients.
Authors: David Yoonsuk Oh, Jason Cham, Li Zhang, Grant Fong, Mark Klinger, Malek Faham, Lawrence Fong
Journal: Journal of Clinical Oncology (2016)

3029 Background: Immune checkpoint inhibitors can elicit clinical responses to a range of tumor types but also significant immune-mediated toxicities (immune-related adverse events, or IRAEs). Both response and toxicity may be mediated by the generation or amplification of specific T cell clones, however it remains unclear whether changes in the T cell receptor (TCR) repertoire after checkpoint blockade are overlapping or distinct for these two outcomes. Methods: Next-generation TCR beta chain sequencing was performed on peripheral blood mononuclear cells from metastatic castrate-resistant prostate cancer patients receiving ipilimumab and GM-CSF as part of a phase I/II trial to assess treatment-induced changes in the TCR repertoire and how they relate to clinical outcomes. Clinical response was defined by a > 50% PSA decline on treatment. Toxicity was defined as any IRAE developing on treatment. Results: We found that treating metastatic cancer patients with ipilimumab leads to T cell repertoire diversification as soon as 2 weeks after the first dose, as measured by a significant change in the clonality index which provides a metric of TCR repertoire diversity at each timepoint. Interestingly, clinical response is significantly correlated with increased repertoire diversity (p = 0.01 for change in clonality between weeks 0 and 2 for PSA responders, p = 0.055 for non-responders). At the same time, development of IRAEs during the study is also significantly correlated with increased diversity (p = 0.023 for change in clonality for IRAE patients, versus p = 0.057 for non_IRAE patients). Repertoire changes in IRAE patients also include increases in the frequency of TCR clones with treatment, including generation of novel clones. Conclusions: Early ipilimumab-induced changes in T cell clonality are associated with both clinical response and toxicity in prostate cancer. These observations are consistent with the overlap that is often seen clinically between clinical responders and IRAEs. Our results indicate that increased repertoire diversity may be a common initial event leading to both beneficial and deleterious outcomes with CTLA-4 blockade.
Sex-hormone-driven innate antibodies protect females and infants against EPEC infection
Authors: Zhutian Zeng, Bas G. J. Surewaard, Connie H. Y. Wong, Christopher Guettler, Bjӧrn Petri, Regula Burkhard, Madeleine Wyss, Hervé Le Moual, Rebekah Devinney, Graham C. Thompson, Jaime Blackwood, Ari R. Joffe, Kathy D. McCoy, Craig N. Jenne, Paul Kubes
Journal: Nature Immunology (2018)
eXalt3: Phase 3 randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients.
Authors: Leora Horn, Yi-Long Wu, Martin Reck, Heather A. Wakelee, Chris Liang, Fenlai Tan, Kimberly Harrow, Vance Oertel, Gary Dukart, Tony Mok
Journal: Journal of Clinical Oncology (2018)

TPS9115 Background: Ensartinib (X-396) is a novel, potent ALK small molecule tyrosine kinase inhibitor (TKI) with additional activity against MET, ABL, Axl, EPHA2, LTK, ROS1 and SLK. Ensartinib is well-tolerated and has shown promising activity in NSCLC patients in a phase 1/2 study in patients that were both ALK TKI naïve and patients that received prior crizotinib, as well as those with CNS metastases. The safety profile of ensartinib appears to be different than other ALK TKIs. Methods: In this global, phase 3, open-label, randomized study, approximately 270 patients with ALK+ NSCLC who have received no prior ALK TKI and up to one prior chemotherapy regimen will be randomized with stratification by prior chemotherapy (0/1), performance status (0-1/2), brain metastases at screening (absence/presence), and geographic region (Asia /other), to receive oral ensartinib (225 mg, once daily) or crizotinib (250mg, twice daily) until disease progression or intolerable toxicity. Eligibility also includes patients ≥ 18 years of age, stage IIIB or IV ALK+ NSCLC. Patients are required to have measurable disease per RECIST 1.1, adequate organ function, and an ECOG PS of ≤2. Adequate tumor tissue (archival or fresh biopsy) must be available for central testing. The primary endpoint is progression-free survival assessed by independent radiology review based on RECIST v. 1.1 criteria. Secondary efficacy endpoints include overall survival, response rates (overall and central nervous system [CNS]), PFS by investigator assessment, time to response, duration of response, and time to CNS progression. The study has > 80% power to detect a superior effect of ensartinib over crizotinib in PFS at a 2-sided alpha level of 0.05. Phase 3 recruitment began in June, 2016 and currently has 98 active sites in 20 countries. The duration of recruitment will be approximately 24 months. This study is registered with. Clinical trial information: NCT02767804.
Understanding Police Use of Force via Hospital Administrative Data
Authors: Ojmarrh Mitchell
Journal: JAMA Network Open (2018)

put forth an innovative examination of legal intervention injuries (ie, police use of force) over an 11-year period in California.The central innovation of this research is the use of administrative data mandatorily reported by license hospitals on all hospital visits made between 2005 and 2015.Such data are a resourceful means of examining police use of force, given that police departments often do not collect such data.From hospital visit data, legal intervention injuries were identified using administrative injury codes.Mooney and colleagues examined trends in injury rates, severity of injuries, and calculated per capita, as well as per arrest rates of legal intervention injuries for males aged 14 to 64 years by race or ethnicity.The analyses found distinct time trends in injury rates and injury severity, both of which generally increased until 2009 and then declined thereafter.