tbuckley/cabot-search huggingface dataset:
Two sequential dose-dense regimens of CGP, followed by MVAC in patients with metastatic urothelial carcinoma (mUC): A single institution, explorative trial.
Authors: Maddalena Donini, Matteo Brighenti, Maria Olga Giganti, Stefano Panni, Bruno Perrucci, Claudio Pizzo, Fabiana Gerevini, Marina Foramitti, Gianluca Marchi, Michele Potenzoni, Andrea Prati, Matteo Quarta, Luigi Benecchi, Carlo del Boca, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2019)

e16023 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active chemotherapy regimens in mUC. We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a single institution, explorative trial. The aim is to evaluate the incremental benefit of the two regimens in terms of complete response and long term survival. We treat all consecutive, chemo-naïve mUC patients with 4 cycles of CGP dose-dense every 14 days followed by 4 cycles of MVAC every 14 days. In all cycles we used Pegfilgrastim 6 mg on day 3. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: From 2007 to 2018, 67 consecutive pts were included. Male were 82%; median age 66 years (33-83); Bajorin risk factors was 0 in 31%, 1 in 52%, 2 in 16%. The majority of pts were hospitalized for three days during chemotherapy and received hydration and supportive therapy. After the first 4 cycles of CGP, we observed 7% CR, 46% PR, 31% SD, and 12% PD. After the 4 sequential cycles of MVAC DD we observed a global 25% of CR, 33% PR, 10% SD, and 24% PD. Median TTP was 8.2 months (95% CI, 7.3-10.1) and median OS was 18 months (95% CI, 10.8-26.1). 5 pts are still alive after more than 30 months and maintaining complete response. Main grade 3–4 toxicity included anemia 27%, asthenia 23%, neutropenia 19% (febrile 7%), thrombocytopenia 13%. Conclusions: The sequential use of these two DD regimens is active and leads to an increased number of complete response and possible longer survival. A randomized trial is needed to confirm our results.
Oncology leadership development using decentralization, task shifting, techno-mentoring and creation of alternate oncology workforce.
Authors: Dinesh Pendharkar
Journal: Journal of Clinical Oncology (2019)

e18043 Background: Access to cancer care remains the greatest challenge world over. One of the solutions include task shifting , decentralization and empowerment of alternate oncology workforce, with health system strengthening. “Pendharkar model “ of cancer care delivery is widely being followed across four states in India and is expanding to two more. It has sustainably created alternate oncology workforce with community oncology leaders. Methods: The model involved creating nodal cancer units in government run district hospitals and creating a physician point of contact for cancer in every unit. The method involved training these general physicians over one month and giving them techno-mentoring backup over every cancer patient they see. They were supposed to play multiple roles including early diagnosis, patient care including chemotherapy, palliative care. One of their role being advocacy and public education. Results: The model led to training of more than 140 physicians and starting of cancer units in about 125 hospitals, with population coverage of more than 200 million population across five states of India. Through their training and mentorship backup they were encouraged to take leading role in the society s cancer advocates, besides care of the cancer patients. In 2018 alone thousands of patients benefited from the services including thousands of courses of chemotherapy. They took up the role of community leaders in oncology. The list of activities performed by them varied from-oncology education and training of the paramedical staff, education of the physicians, cancer counselling camps, designing educational material, public educational meeting, rallies , leaflet distributions, multiple press and TV – mass media presentations on cancer, organizing cancer related painting exhibitions, slogan campaigns and so on. World cancer activities were simultaneously observed in more than 100 districts in last two consecutive years. Conclusions: The model as by product led to the creation of an huge army oncology leaders in the community. The general physicians from periphery turned in to powerful cancer advocates.
Association Between the Publication of the Initiating Dialysis Early and Late Trial and the Timing of Dialysis Initiation in Canada
Authors: Thomas W. Ferguson, Amit X. Garg, Manish M. Sood, Claudio Rigatto, Elaine Chau, Paul Komenda, David Naimark, Gihad E. Nesrallah, Steven D. Soroka, Monica Beaulieu, Ahsan Alam, S. Joseph Kim, Stephanie Dixon, Braden Manns, Navdeep Tangri
Journal: JAMA Internal Medicine (2019)

Published in 2010, the Initiating Dialysis Early and Late (IDEAL) randomized clinical trial, which randomized patients with an estimated glomerular filtration rate (GFR) between 10 and 15 mL/min/1.73 m2 to planned initiation of dialysis with an estimated GFR between 10 and 14 mL/min/1.73 m2 (early start) or an estimated GFR between 5 and 7 mL/min/1.73 m2 (late start), concluded that early initiation was not associated with improved survival or clinical outcomes.To assess the association between the IDEAL trial results and the proportion of early dialysis starts over time.This interrupted time series analysis used data from the Canadian Organ Replacement Register to study adult (≥18 years of age) patients with incident chronic dialysis between January 1, 2006, and December 31, 2015, in Canada, which has a universal health care system. Patients from the province of Quebec were excluded because its privacy laws preclude submission of deidentified data without first-person consent. The patients included in the study (n = 28 468) had at least 90 days of nephrologist care before starting dialysis and a recorded estimated GFR at dialysis initiation. Data analyses were performed from November 2016 to January 2019.The primary outcome was the proportion of early dialysis starts (estimated GFR >10.5 mL/min/1.73 m2), and the secondary outcomes included the proportions of acute inpatient dialysis starts, patients who started dialysis using a home modality, and patients receiving hemodialysis who started with an arteriovenous access. Measures included the trend prior to the IDEAL trial publication, the change in this trend after publication, and the immediate consequence of publication.The final cohort comprised 28 468 patients, of whom 17 342 (60.9%) were male and the mean (SD) age was 64.8 (14.6) years. Before the IDEAL trial, a statistically significant increasing trend was observed in the monthly proportion of early dialysis starts (adjusted rate ratio, 1.002; 95% CI, 1.001-1.004; P = .004). After the IDEAL trial, an immediate decrease was observed in the proportion of early dialysis starts (rate ratio, 0.874; 95% CI, 0.818-0.933; P < .001), along with a statistically significant change in trend between the pretrial and posttrial periods (rate ratio, 0.994; 95% CI, 0.992-0.996; P < .001). No statistically significant differences were found in acute inpatient dialysis initiations, the proportion of patients receiving home dialysis as the initial modality, or the proportion of arteriovenous access creation at hemodialysis initiation after the IDEAL trial publication.The publication of the IDEAL trial appeared to be associated with an immediate and meaningful change in the timing of dialysis initiation in Canada.
Contextualizing place and health in rural America: Cancer information seeking across four categories of an urban/rural continuum.
Authors: Gilberto Lopez, Heather Mattie, Eva Culakova, Po-Ju Lin, Charles Stewart Kamen, Michelle Christine Janelsins, Gary R. Morrow
Journal: Journal of Clinical Oncology (2019)

e18124 Background: Cancer is the second leading cause of death in the United States. Despite decreases in cancer mortality overall, rural populations continue to have higher prevalence and slower reduction of cancer death rates. As a preventive approach to combat cancer, the National Cancer Institute continues to prioritize providing the public with health information. Yet, little is known about cancer information-seeking across rural America. Methods: Using Rural-Urban Commuting Area Codes (RUCAs), from the 2018 Health Information National Trends Survey (HINTS-5) database we analyze the odds of looking for information about cancer across four geo-political contexts (n = 2,625): urban, large-rural, small-rural, and isolated-rural areas, thus giving us a potentially more detailed understanding of place and health across the urban-rural continuum. Using an established social determinants framework, a series of logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (CIs). Results: Across all models, those living in large rural towns had about 1.5 times the odds of looking for cancer information compared to urban-dwellers (p &lt; 0.05) while those living in remote rural areas had about 0.5 times the odds (p &lt; 0.05). There was no difference for those living in small rural towns. Additionally, gender, race/ethnicity, marital status, education, housing status, and internet availability were independently associated with information-seeking (p &lt; 0.05). Conclusions: In this study, compared to urban-dwellers, those living in large rural towns appeared to have increased odds of looking for cancer information while those living in isolated rural areas had decreased odds. Understanding this relationship between place and health has implication for the allocation of resources and the design of interventions aimed at increasing information about cancer.
Trends of endometrial cancer incidence from 2000 to 2015 in the United States.
Authors: V V Pavan Kedar Mukthinuthalapati, Muhammad Zain Farooq, Shweta Gupta
Journal: Journal of Clinical Oncology (2019)

5591 Background: Recent studies have shown that obesity related cancers are increasing in incidence in the US as the rates of obesity rise and some cancers, like colorectal cancer, are occurring in younger age groups. We studied trends in incidence of endometrial cancer (EC), one of the obesity related cancers, in a population wide analysis. Methods: We analyzed data from all cases of EC between 2000 and 2015 from 18 US cancer registries using the National Cancer Institute’s Surveillance, Epidemiology and End Results Program. SEER*Stat was used to query the database for annual percent changes (APC), incidence ratios and percent change in incidence across different age groups, years of diagnosis, histologic subtypes, grade and race. We also studied the reported rates and trends of obesity in the US. Results: APC of age-adjusted EC incidence between 2000 and 2015 was +0.9% (95% confidence interval (CI) 1.1-0.6, p value&lt;0.05). Incidence of EC rose from 17.8 per 100,000 to 19.7 per 100,000 during the same duration. APC for EC incidence for age groups 20-39 and &gt;40 were +3.2% (p-value &lt;0.05) and +0.8% (p value &lt;0.05), respectively. For the age-group 20-39, endometrioid EC was the only histologic subtype that rose in incidence, with an APC of +5.5% and absolute percentage change of 156%. The APC of EC in 20-39 age group was more for whites (3.5%, p-value&lt;0.05) and Asians (2.2%, p-value&lt;0.05) than blacks (1.8, p-value &lt;0.05). CDC reported an increase in obesity rates in adults from 30.5% in 2000 to 37.7% in 2014. Table shows trends of EC incidence in age groups 20-39 and &gt;40 years across various histologic subtypes. (Abbreviations: S significant, NS not significant, NC non-calculable). Conclusions: Endometrial cancer, especially of endometrioid histology, is increasing in incidence and is occurring more often in the younger population. The concomitant rise in obesity rates during the same period point towards a possible causality of the increased in incidence of EC. Population based strategies are needed to decrease the trends in obesity so as to decrease the risk of endometrial cancer in younger women. [Table: see text]
A phase I open prospective cohort trial of curcumin plus tyrosine kinase inhibitors for EGFR-mutant advanced non-small cell lung cancer.
Authors: Khashayar Esfahani, Levon Boodaghians, Goulnar Kasymjanova, Jason Scott Agulnik, Carmela Pepe, Lama Sakr, David I. Small, Tomas R. Jagoe, Victor Cohen
Journal: Journal of Clinical Oncology (2019)

e20611 Background: An increasing number of patients with lung cancer use natural products concurrently with conventional treatments, one of which is curcumin, or diferuloylmethane, the main ingredient in the popular spice known as curry. Curcumin has been shown to have anti-carcinogenic effects on human lung cancer cell lines and in vivo models, as well as the potential to modulate all three known pathways accounting for resistance to EGFR-TKIs. More specifically, curcumin dose-dependently suppresses EGFR expression, reduces transactivation of the MET oncogene, and reduces inflammation in the tumor microenvironment by selectively inhibiting TGF-β, IL-6, C-reactive protein (CRP) as well as TNF-α. Despite these promising findings, no studies have yet assessed the safety of introducing curcumin alongside EGFR-TKIs in a lung cancer population. Methods: We performed a phase 1 open prospective cohort study to assess the safety and feasibility of using an enhanced bioavailable formulation of curcumin (CURCUViva TM at 80 mg/ 1 capsule per day) approved and licensed by Health Canada (NPN 80027414) in conjunction with an EGFR-TKI in patients with advanced NSCLC (ClinicalTrials.gov: NCT02321293). The primary objective was to determine safety and feasibility. Exploratory objectives were monitoring changes in health-related quality of life using the standardized FACT-L questionnaire and evaluating anti-inflammatory properties of curcumin by measuring CRP. Results: 55 patients were approached, of whom 75% were interested in using curcumin. Completion rate (80%) and adherence (82%) levels were very high; most patients perceived the product as easy to take and were willing to take it again if it were available. Nine patients refused to participate solely due to frequent clinic visits. A total of 37 adverse events were reported, all of which were mild (Grade 1 or 2). The vast majority were pre-existing and related to TKI treatment. No biochemical or hematological evidence of toxicity was observed. Overall, there was improvement in quality of life, and improvement in the LCS of the FACT-L (p = 0.06). There was no significant change in CRP levels. Conclusions: This study provides preliminary evidence that short-term use of curcumin in EGFR-positive patients treated with TKIs is feasible and safe. We report high treatment adherence and improved quality of life with curcumin. These findings, as well as efficacy data and the effect of curcumin on other inflammation-associated biomarkers, warrant investigation in a larger phase 2 study. Clinical trial information: NCT02321293.
Are two sites better than one?: Sites of care and quality of myeloma treatment.
Authors: Anne Renteria, Sundar Jagannath, Kezhen Fei, Sylvia Lin, Radhi Yagnik, Lisa La, Jenny J. Lin, Nina A. Bickell
Journal: Journal of Clinical Oncology (2019)

e18159 Background: Care coordination affects the quality of cancer treatment. Multiple Myeloma (MM) patients frequently are cared for by local and referral center physicians. We sought to determine whether getting treated at different sites might impact on the quality of MM care. Methods: We used NCCN 2014 and CMS guidelines to define categories of treatment quality and transplant eligibility. We defined high quality MM care as: Induction for all patients with ECOG &lt; 4; harvest &amp; transplant for patients completing induction without progression, with albumin &gt; 2.8, bilirubin &lt; 3 and age ≤77 years; maintenance for transplant ineligible patients completing induction with no progression &amp; for transplant eligible patients completing transplant with no progression; and supportive care of receiving bone targeting agents, anticoagulation and infection prophylaxis for all patients receiving MM therapy. Patients who received care with both local and referral center physicians were considered to have received care at 2 sites. We abstracted 709 charts of patients with ICD-9 diagnosis of MM from 2010-2014 for demographics, site of care and treatments received. We compared groups with chi square and multivariate logistic regression models with age, insurance, race, comorbidity and sites of care to predict care quality. Results: Of the 709, 388 had active MM. On average, patients were 62 ±11 years. Overall, 70% received care at &gt; 1 site. Referred patients had no differences by age, comorbidity index, insurance or race. Having &gt; 1 care site was associated with higher rates of induction and harvest. Conclusions: Historically, hand-offs in care have been associated with poorer quality. However, in a referral center, hand-offs do not negatively affect induction and harvest care quality. Patients referred to a MM center are more likely to get high quality treatments for which they are referred, but referral does not ensure receiving the full gamut of needed MM treatments.[Table: see text]
Effect of germline ATM mutations on clonal hematopoiesis.
Authors: Thomas Paul Slavin, Kar Wing Kevin Tsang, Jeffrey Longmate, Danielle Castillo, Josef Herzog, Hanjun Qin, Jinhui Wang, Susan L. Neuhausen, Rosa Mejia, Elisabeth King, Milhan Telatar, Catherine A Marcum, Carolyn B. Hendricks, Christopher R. Hake, Victoria Louise Seewaldt, Joseph Geradts, Jeremy Stark, Guido Marcucci, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2019)

1509 Background: Clonal hematopoiesis (CH) in myeloid related-genes is associated with development of primary and secondary leukemia and atherosclerotic disease, as well as, decreased overall survival. Identification of factors beyond age and cytotoxic exposures that predispose to CH may be useful to both recognize individuals at increased risk for CH and to better understand how CH develops. We have previously shown that germline mutations in the DNA repair gene ATM may predispose to CH. We hypothesized here that heterozygous ATM germline mutation carriers would have higher rates of CH in myeloid genes compared to controls. Methods: Germline DNA samples from 34 heterozygous ATM germline mutation carriers (cases) and 22 controls without ATM germline mutations were sequenced on an Illumina 2500 using a custom 79-gene-myeloid-CH-coding-exon-amplicon-based Qiaseq panel. Read depth averaged 130x. Pathogenic and likely pathogenic CH variants (PV) above an allele fraction of 2% were used for analyses. Cases and controls were compared using a rank-sum test. Results: Cases had a higher median age (56 years, range 30-82) than controls (48 years, range 5-72). Cases and controls were similar in solid tumor cancer history and known exposure to cancer cytotoxic therapy; 73.5% vs 86.4%, and 18.1 vs 20.6%, respectively. The number of CH PV was similarly associated with age in both cases and controls (cor = 0.31, p = 0.01). Cases displayed more CH PVs than controls (total 62 vs 3 PVs, median 2 PVs vs 0, p = 10 -6 ). Of note, cases frequently had a concomitant second (n = 10; 29% of cases) or third (n = 4; 11.8% of cases) unique ATM CH PV, whereas no ATM CH PVs were seen in controls. Even after excluding ATM CH PVs, CH PVs were more frequent in cases (p = 0.00003). After ATM CH PVs, the most frequent CH PVs in cases were in NF1 (5 PVs), BCORL1 (4 PVs), and DMNT3A (4 PVs). Conclusions: Our study supports ATM as a strong predisposition locus for myeloid gene CH. CH in ATM germline mutation carriers frequently involved unique low allele fraction PVs in ATM, suggesting ATM germline PVs are driving production of likely bi-allelic ATM inactivation in white blood cells, or complete ATM loss. Complete ATM loss may be a nidus particularly for lymphocytic leukemia, as bi-allelic ATM inactivation is a frequent somatic finding.
Afatinib versus methotrexate as second-line treatment for patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) progressing on or after platinum-based therapy: LUX-Head &amp; Neck 3 phase III trial.
Authors: Ye Guo, Myung-Ju Ahn, Anthony T. C. Chan, Cheng-Hsu Wang, Jin Hyoung Kang, Sung-Bae Kim, Maximino De Guzman Bello, Rajendra Singh Arora, Qingyuan Zhang, Xiaohui He, Ping Li, Arunee Dechaphunkul, Vijay Kumar, Krishna Kamble, Wei Li, Alaa Kandil, Ezra E.W. Cohen, Yuan Geng, Lef Zografos, Ping Zhang Tang
Journal: Journal of Clinical Oncology (2019)

6024 Background: In a previous global phase III trial (LUX-Head &amp; Neck 1), second-line (2L) afatinib significantly improved PFS vs methotrexate (MTX) in pts with R/M HNSCC. Here, we compared efficacy/safety of 2L afatinib vs MTX in Asian pts with R/M HNSCC. Methods: Pts progressing on/after platinum therapy were randomized (2:1) to 40 mg/day afatinib (feeding tube or oral) or 40 mg/m 2 /week iv MTX. Primary endpoint was PFS by independent review. Secondary endpoints were OS, ORR, and patient-reported outcomes. Results: 340 pts were randomized (afatinib 228, MTX 112). Median (range) duration of treatment (Tx) was 3.0 ( &lt; 0.1–35.9) and 1.4 ( &lt; 0.1–8.8) mos, respectively. Afatinib significantly decreased the risk of progression or death by 37% compared with MTX (HR 0.63; 95% CI: 0.48, 0.82 p = 0.0005, median PFS, 2.9 vs 2.6 mos; landmark analysis at 12 and 24 wks, 58 vs 41%, 21 vs 9%). There was no significant difference in OS (HR 0.88; 95% CI: 0.68, 1.13; median 6.9 vs 6.4 mos). ORR was 28% with afatinib and 13% with MTX (OR 2.8; 95% CI: 1.5, 5.2, p = 0.016). More pts had clinically relevant improvements in global health status/quality of life (GHS/QoL; 40 vs 23%, p &lt; 0.01), swallowing (34 vs 18%, p = 0.01) and pain (34 vs 25%, p = 0.22) with afatinib vs MTX. Post-baseline change in GHS/QoL score was more favorable with afatinib (p &lt; 0.001). Treatment-related adverse events (TRAEs; all/grade ≥3) were reported in 89/16% and 67/23% pts with afatinib and MTX. The most common grade ≥3 TRAEs were rash/acne (4%), diarrhea (4%), and stomatitis (3%) with afatinib, and anemia, leukopenia, and fatigue (all 5%) with MTX. Fatal AEs were reported in 23 and 11% pts with afatinib and MTX. Two ( hypoglycemia, pneumonitis/lung infiltration) and 4 pts had fatal AEs considered related to Tx with afatinib and MTX. 11% and 17% pts discontinued Tx due to TRAEs. Conclusions: LUX-Head &amp; Neck 3 achieved its primary endpoint. Two randomized phase III trials have now demonstrated clinical benefit with 2L afatinib vs MTX. Safety data were consistent with the known tolerability profiles of afatinib and MTX. Clinical trial information: NCT01856478.