tbuckley/cabot-search huggingface dataset:
Phase II study of the PD1-inhibitor pembrolizumab for the treatment of relapsed or refractory mature t-cell lymphoma.
Authors: Stefan K. Barta, Jasmine M. Zain, Sonali M. Smith, Jia Ruan, Henry C. Fung, Carlyn R Tan, Yibin Yang, R. Katherine Alpaugh, Eric A. Ross, Kerry S. Campbell, Nadia Khan, Richard I. Fisher, Yasuhiro Oki
Journal: Journal of Clinical Oncology (2018)

7568 Background: PDL-1 is often expressed on tumor cells or in the microenvironment of T-cell NHL (Wilcox RA. Blood 2009) making inhibition of the PD1/PDL-1 axis a rational treatment target for T-cell NHL. Methods: We evaluated monotherapy with the PD1-inhibitor pembrolizumab (200mg flat dose q3weeks) for pts aged ≤18 with relapsed or refractory mature T-cell NHL in a multicenter prospective phase II trial. Primary endpoint was median progression-free survival (mPFS) defined as time from enrollment to either death or progression. The study was powered to demonstrate an improvement in mPFS from 3 to 6 months. Results: 18 pts were enrolled and included in the safety analysis. 17 pts were included in the survival analysis as 1 pt was found ineligible after central path review (n = 7 PTCL-NOS; n = 3 follicular T-cell lymphoma; n = 3 transformed MF; n = 1 MEITL, HSTCL, and AITL each; n = 1 ineligible histology). 2 pts came off study prior to response assessment for toxicities leaving 15 pts evaluable for response. Median age was 71 (18-88); 47% were male; median number of prior therapies was 2 (1-9); 76% were refractory to their last treatment. Response rate was 27% (4/15 pts; 95%CI 5-49%). All 4 responders (ALCL, MF, PTCL-NOS, FTCL) achieved a CR and were pts who had received ≤2 prior therapies. PDL1-expression was higher in responders, though not significantly (H-score 115 vs 68; p = 0.68). Median response duration was not reached with 2 of 4 responses ongoing > 9 months; 2 pts came off study in CR (n = 1 at 6 wks for toxicity; n = 1 at 6 mo for transplant). Median PFS and OS were 3.2 (95%CI 1.2-3.7) and 10.6 months (95%CI 3.2-100) respectively, with a median follow up of 5.9 months. 88% discontinued treatment early for PD (44%), toxicity (22%), pt choice, investigator choice, or transplant (6% each). Rash was the most common treatment attributable adverse event (AE) in 17% (n = 3). Most common AE ≥G3 were pneumonitis and rash (11% each). Treatment attributed SAE occurred in 11% (pneumonitis: n = 1; vasculitis: n = 1). Immune-related AE ≥G3 occurred in 5 pts (pneumonitis, rash: n = 2 each; vasculitis: n = 1). Conclusions: Pembrolizumab has moderate activity in T-cell NHL with acceptable toxicities. Combination therapies are being actively explored. Clinical trial information: NCT02535247.
Chimeric antigen receptor-t cells (CAR-T) horizon scanning: Emerging targets in oncology and hematology.
Authors: Quentin Dardonville, Claire Davoine, Muriel Dahan, Ghislain Grosjean, Elisabeth Bermudez, Norbert Ifrah, Sophie Negellen
Journal: Journal of Clinical Oncology (2018)

e15031 Background: The launch of CAR-T cells raises major issues in terms of therapeutic strategies, safety, organization of care, financial sustainability. Regarding these challenges and the strong innovative character of CAR-T cells, the French National Cancer Institute has conducted a horizon scanning to identify CAR-T cells targets and their potential impact in clinical practices. Methods: Active CAR-T cells clinical trials (CT) were extracted in July 2017 from clinicaltrial.gov database. For each CT, the following criteria were collected: phase of the trial, target, population, tumor localization. Results: 189 CT involving CAR-T cells were identified, representing about 7700 patients included, essentially in early phases: 51% of CT in phase I and 43% in phase I-II. A significant part of CT assessed CAR-T cells in pediatric population (39%). 67% of CT concerned hematology and 31% solid tumour (2% both localization). 97% of CT were developed for a specific target, only 3% being multi-targets. 36 targets were identified, most frequently involving : CD19 (87 CT) in B-cells malignancies ; mesothelin (12 CT) in solid tumours (pancreatic, ovarian, breast and pleural mesothelioma) ; EGFR (8 CT) in solid tumour, CD30 (8 CT) in hematology ; HER2 (6 CT) in solid tumour ; GD2 (5 CT) in neuroblastoma and CD123 (5 CT) in acute myeloid leukemia ; BCMA (4 CT) ; CD22 (4 CT) ; CD33 (4 CT) ; GPC3 (4 CT) ; MUC1 (4 CT) ; CEA (3 CT) ; CD138 (2 CT) ; EpCAM (2 CT) ; NKG2D (2 CT) ; PSMA (2 CT). Some new CAR-T cells combined two targets as CD 19-22 (2 CT) and CD 19-20 (1 CT) in hematology. Conclusions: This horizon scanning observes the significant expansion of the CAR-T cells panel in terms of targets and cancers involved. Since most situations correspond to an unmet medical need, each country must anticipate the arrival of similar innovation, including major ethical and economic issues.
Variation in Childhood Diarrheal Morbidity and Mortality in Africa, 2000–2015
Authors: Robert C. Reiner, Nicholas Graetz, Daniel C. Casey, Christopher Troeger, Gregory M. Garcia, Jonathan F. Mosser, Aniruddha Deshpande, Scott J. Swartz, Sarah E. Ray, Brigette F. Blacker, Puja C. Rao, Aaron Osgood-Zimmerman, Roy Burstein, David M. Pigott, Ian M. Davis, Ian D. Letourneau, Lucas Earl, Jennifer M. Ross, Ibrahim A. Khalil, Tamer H. Farag, Oliver J. Brady, Moritz U.G. Kraemer, David L. Smith, Samir Bhatt, Daniel J. Weiss, Peter W. Gething, Nicholas J. Kassebaum, Ali H. Mokdad, Christopher J.L. Murray, Simon I. Hay
Journal: New England Journal of Medicine (2018)

Diarrheal diseases are the third leading cause of disease and death in children younger than 5 years of age in Africa and were responsible for an estimated 30 million cases of severe diarrhea (95% credible interval, 27 million to 33 million) and 330,000 deaths (95% credible interval, 270,000 to 380,000) in 2015. The development of targeted approaches to address this burden has been hampered by a paucity of comprehensive, fine-scale estimates of diarrhea-related disease and death among and within countries.We produced annual estimates of the prevalence and incidence of diarrhea and diarrhea-related mortality with high geographic detail (5 km2) across Africa from 2000 through 2015. Estimates were created with the use of Bayesian geostatistical techniques and were calibrated to the results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016.The results revealed geographic inequality with regard to diarrhea risk in Africa. Of the estimated 330,000 childhood deaths that were attributable to diarrhea in 2015, more than 50% occurred in 55 of the 782 first-level administrative subdivisions (e.g., states). In 2015, mortality rates among first-level administrative subdivisions in Nigeria differed by up to a factor of 6. The case fatality rates were highly varied at the national level across Africa, with the highest values observed in Benin, Lesotho, Mali, Nigeria, and Sierra Leone.Our findings showed concentrated areas of diarrheal disease and diarrhea-related death in countries that had a consistently high burden as well as in countries that had considerable national-level reductions in diarrhea burden. (Funded by the Bill and Melinda Gates Foundation.).
Suicide in India: a complex public health tragedy in need of a plan
Authors: Gregory Armstrong, Lakshmi Vijayakumar
Journal: The Lancet Public Health (2018)

Suicide is a major public health problem, with far-reaching socioeconomic, political, and emotional consequences. Southeast Asia accounts for roughly 40% of the estimated 800 000 annual suicide deaths globally,1 and is the frontline for delivering on the aspirational Sustainable Development Goal (SDG) of a one-third reduction in the suicide death rate (SDR) by 2030.
Cancer-related fatigue in breast cancer survivors: A longitudinal analysis compared to matched controls.
Authors: AnnaLynn Williams, Charles E. Heckler, Carly Lynn Paterson, Debra L. Barton, Kelley Lynn Young, Alison Katherine Conlin, Lora Rose Weiselberg, Karen Michelle Mustian, Luke Joseph Peppone, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2017)

10045 Background: Cancer related fatigue (CRF) is commonly reported among breast cancer survivors and can negatively impact quality of life and treatment adherence. Large, prospective, longitudinal studies assessing CRF in breast cancer survivors compared to matched non-cancer controls are rare. Methods: Breast cancer survivors (n = 581, stage I-IIIBC, mean age 53.4) from community oncology clinics and age-matched controls (n = 364, mean age 52.6) completed the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI, scores range -24 to 96) prior to chemotherapy (T1), at chemotherapy completion (T2) and six-months after chemotherapy (T3). Linear mixed models compared trajectories of CRF over time in survivors compared to controls, adjusting for age, education, race, BMI, marital status, menopausal status, and depressive symptoms. Results: Survivors reported greater CRF compared to controls at all time points (mean total score T1 9.4 vs. -3.7, T2 17.0 vs. -3.3, and T3 8.5 vs. -3.1, all p &lt; 0.001; all subscales p &lt; 0.001). From T1 to T2 survivors experienced a significant increase in CRF as shown in the total score (mean change (MC) = 8.3; effect size (ES) = 0.4 , p &lt; 0.001), and general, mental, and physical sub-scales (MC = 4.3, 2.1, 3.2 , ES = 0.7, 0.5, 0.7, respectively, all p &lt; 0.001), while controls experience minimal changes (MC = 0.1-0.3, ES &lt; 0.09, p &gt; 0.05). At T3 survivors total score returned to T1 values (MC = -0.1, ES = 0.01, p = 0.461), which was, however, still greater than controls ( p &lt; 0.001), while general, mental, and physical CRF subscale scores remained significantly higher than T1 values (MC = 1.2, 1.7, 1.9, ES = 0.2, 0.4, 0.3, respectively, all p &lt; 0.001; controls no change). Group by time interactions indicated changes over time were greater in the survivors than controls (p &lt; 0.001). In multivariate analyses of survivors, age, BMI, performance status, and baseline depression significantly predicted change in CRF. Conclusions: These results from the largest well-controlled study to date showed that breast cancer survivors experience significantly more CRF prior to and after chemotherapy compared to healthy controls. Further research should aim to identify subgroups of survivors most susceptible to CRF.
Avelumab and cetuximab in combination with FOLFOX in patients with previously untreated metastatic colorectal cancer (MCRC): The phase II AVETUX-CRC trial (AIO KRK 0216).
Authors: Alexander Stein, Mascha Binder, Carsten Bokemeyer, Salah Eddin Al Batran, Axel Hinke, Susanna Hegewisch-Becker
Journal: Journal of Clinical Oncology (2017)

TPS3620 Background: Inhibition of the PD-1/L1 axis has shown to improve survival as single agent in a variety of tumor types. The efficacy of single agent PD-1/L1 inhibition in patients with treatment refractory MCRC seems to be limited to hypermutated tumors characterized by mismatch repair deficiency. 1 st line chemotherapy (e.g. FOLFOX) with cetuximab for patients with RAS/BRAF wildtype MCRC result in objective response rates of about 60%, thus substantial antigen release will likely occur triggering immune control. Furthermore, the induction of immunogenic cell death has been recently shown for cetuximab-based regimen. Thus, the evaluation of FOLFOX and cetuximab in combination with avelumab in 1 st line MCRC is of particular interest. Methods: AVETUX is a single arm exploratory phase II investigator initiated trial. Patients with RAS/BRAF wildtype MCRC will be included independent of mismatch repair status to receive mFOLFOX6 and cetuximab in combination with avelumab (10mg/kg from day 1 of cycle 2 onwards). Treatment with avelumab is limited to a maximum of 18 months. Primary endpoint is 12month progression-free survival rate, which should be increased from 40% to 57%, with type I error of 10% and 80% power, leading to a sample size of 43 patients. An early stopping rule will be applied in case of an increase in toxicity after the first 15 patients received at least two months of treatment. The trial is flanked by a large translational program including immunoprofiling to determine and correlate the respective immune response signatures with clonal dynamics (RAS/EGFR). Recruitment will start in 11 German sites early 2017. Clinical trial information: EudraCT No 2016-004434-26. Conclusion: The AVETUX trial will determine the feasibility and early efficacy of FOLFOX and cetuximab combined with avelumab in 1 st line MCRC. The translational research program will shed light on the potential mode of action of this novel combination. Clinical trial information: 2016-004434-26.
The emotional journey among caregivers of patients with leukemia: The caregivers’ perspective using social media listening.
Authors: Susan Gabriel, Kerri Phillips, Mary Ann Slater, Jifang Zhou, Ashutosh K. Pathak, Lulu K. Lee
Journal: Journal of Clinical Oncology (2017)

e18568 Background: The burden of cancer has largely focused on the patient. However, caregivers also experience considerable burden. The study's aim was to use social media posts to better understand the emotional journey of caregivers who provide care for patients with leukemia from their own perspective. Methods: Publicly available social media posts (in English) mentioning chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and acute promyelocytic leukemia (APL) from blogs, discussion boards, and Facebook were collected and linguistically analyzed. Results: A total of 145 social media posts by CML caregivers, 149 posts by CLL caregivers, and 65 posts by APL caregivers were analyzed. Common themes emerged among CML, CLL, and APL caregivers as they journeyed from pre-diagnosis, to diagnosis, and to survivorship alongside their loved ones. At the pre-diagnosis phase, caregivers expressed uneasiness or worry about the symptoms their loved ones were experiencing. Additionally, caregivers were often frustrated with doctors because they felt that their loved ones’ symptoms were ignored, which led to a delay in diagnosis. Once the diagnosis was confirmed, caregivers were shocked and scared. Further, caregivers were desperate for information on the disease and what the future would hold. During the survivorship phase of the journey, an amalgam of complex positive and negative emotions emerged among caregivers. Caregivers can become obsessed with finding ways to treat their loved ones, including use of alternative medicine. Caregivers experienced both positive (a more “enriched relationship”) and negative (felt alone or pushed away) relationship changes. Many caregivers were proud of their loved ones’ remission and felt triumphant. Caregivers felt a sense of gratitude toward doctors, friends, family, and social media sites for their support. Conclusions: Caregivers of CML, CLL, and APL patients experience a gamut of emotions at every stage of the disease. Additionally, the relationship between caregivers and loved ones can be negatively affected. Findings suggest that relationship counseling and social support groups could potentially relieve some caregiver burden.
Bioresorbable pressure sensors protected with thermally grown silicon dioxide for the monitoring of chronic diseases and healing processes
Authors: Jiho Shin, Ying Yan, Wubin Bai, Yeguang Xue, Paul Gamble, Limei Tian, Irawati Kandela, Chad R. Haney, William Spees, Yechan Lee, Minseok Choi, Jonathan Ko, Hangyu Ryu, Jan-Kai Chang, Maryam Pezhouh, Seung-Kyun Kang, Sang Min Won, Ki Jun Yu, Jianing Zhao, Yoon Kyeung Lee, Matthew R. MacEwan, Sheng-Kwei Song, Yonggang Huang, Wilson Z. Ray, John A. Rogers
Journal: Nature Biomedical Engineering (2018)
Anaplastic lymphoma kinase (ALK) positive tumors: Clinical, radiographic and genomic characteristics, and unusual sites of metastases.
Authors: Rohan Gupta, Idoroenyi Usua Amanam, Ravi Salgia, Isa Mambetsariev, Yingyu Wang
Journal: Journal of Clinical Oncology (2018)

e21130 Background: ALK gene rearrangements are observed in about 4-8% Non-small cell lung cancer (NSCLC). Due to low incidence there is limited knowledge about patterns of metastasis in ALK+ tumors. Our primary objective was to determine the unique sites of metastasis of ALK+ NSCLC. Secondary objectives included study of coexisting mutations, radio- genomics and factors impacting survival of ALK+ NSCLC. Methods: All patients with metastatic ALK+ NSCLC at the City of Hope Cancer Center in Duarte, California from 2012-2017 were selected for retrospective chart review. The demographic variables included age, sex, race, date of birth, vital status, histological diagnosis, number of prior lines of therapy and types of therapy. The molecular statuses of patients were evaluated through commercially available platforms for next-generation sequencing (NGS). 3-D volumetric images were generated by two experienced radiologists for the primary lesion and different sites of metastasis. Results: 62 patients with ALK+ NSCLC were identified from 2012-2017. The median age was 59 with 58% females and only 32% smokers. 95% of ALK+ tumors were adenocarcinomas. Treatments included chemotherapy (92%), crizotinib (95%), alectinib (40%), brigatinib (11%), immunotherapy (18%) or clinical trials (24%). 24 patients had unusual sites of metastasis which were thyroid, soft tissue, chest and abdominal wall, spleen, peritoneum, omentum, kidney and ovary. Common characteristics of the primary lesions were RUL location (39%), oval shape (37%), irregular margins (44%), solid lesions (46%), presence of pleural contact or effusion (51%). 25/62 patients had NGS testing which showed co-existing mutations such as TP53 (n = 8), EGFR (6), KRAS (4). Patients with unusual sites of metastasis had a decreased median survival compared to common sites (39 m vs. 82 m, p = 0.046). Conclusions: In NSCLC, ALK rearrangements are not mutually exclusive mutations and can present with unique radiographic patterns. Patients with unusual sites of metastasis have poor outcomes. 3-D volumetric images can be used with NGS testing to establish a distinct radio-genomic signature which can help with non-invasive treatment planning.
A meta-analysis of trials of etoposide plus platinum agent versus irinotecan/topotecan plus platinum agent in first-line therapy of extensive stage small cell lung cancer (ES SCLC).
Authors: Peter Michael Ellis, Lisa Durocher-Allen, Emily Vella, Alexander Sun, Yee Ung, Kevin Ramchandar, Gail Elizabeth Darling, John R. Goffin
Journal: Journal of Clinical Oncology (2017)

e20019 Background: Etoposide plus a platinum agent (EP) represents the standard treatment of ES SCLC. A trial conducted in Japan demonstrated improved overall survival (OS) for irinotecan and cisplatin (IP), but subsequent trials could not consistently replicate these findings. Genotypic differences may explain these findings. These trials have not undergone systematic analysis. Methods: We conducted a systematic review and metaanalysis of randomized trials (RCT) comparing etoposide plus a platinum agent (EP) with irinotecan (IP) or topotecan (TP) plus a platinum agent. A literature search was undertaken of Cochrane Database, MEDLINE and Embase from 1996 to June 2016 to identify RCTs addressing this question. Data were extracted by one author and checked independently, then synthesized using RevMan software using a random effects model. Outcomes of interest were OS, quality of life (QoL) and toxicity. Results: Three RCTs compared TP and EP. There was no difference in OS (HR 0.97, 95%CI 0.87 – 1.07). Eight RCTs compared IP and EP, although only 7 had data that could be combined. IP significantly improved OS compared with EP (HR 0.84, 95%CI 0.74 – 0.95). The estimated improvement in 12 month OS is 6.4%. There was evidence of statistical heterogeneity. After removal of the trial by Noda et al, there was still a significant improvement in OS (HR 0.88, 95%CI 0.79 – 0.98). IP was associated with less grade 3/4 neutropenia, febrile neutropenia, anemia, thrombocytopenia, but more diarrhea. QoL was assessed in 2 trials and no differences observed. Conclusions: IP results in modest improvements in OS in comparison with EP. IP is associated with less hematological toxicity but more diarrhea and should be considered an acceptable alternative to EP in the first-line treatment of ES SCLC. [Table: see text]
Different upper airway microbiome and their functional genes associated with asthma in young adults and elderly individuals
Authors: Jin‐Jae Lee, Sae‐Hoon Kim, Min‐Jung Lee, Byung‐Keun Kim, Woo‐Jung Song, Heung‐Woo Park, Sang‐Heon Cho, Soo‐Jong Hong, Yoon‐Seok Chang, Bong‐Soo Kim
Journal: Allergy (2018)

Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma.Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non-asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high-throughput sequencing.The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non-asthmatics in each age group. Different bacteria were related to FEV1% predicted in each age group. Genes related to lysine degradation, N-glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non-asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis-which may all be related to increased inflammation and colonization of pathogenic bacteria-were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity.These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.