tbuckley/cabot-search huggingface dataset:
A community hospital experience in the use of peri-operative dose-dense MVAC in patients with muscle-invasive bladder cancer (MIBC) treated with either robotic cystectomy (RC) or open cystectomy (OC).
Authors: Sukesh Manthri, Bruno R. Bastos
Journal: Journal of Clinical Oncology (2014)

e15509 Background: Community practices have shied away in using DD-MVAC as neo-adjuvant regimen of choice to treat MIBC. Recent data has shown that DD-MVAC has better tolerability than standard MVAC and its use has now being advocated in the neo-adjuvant setting. Most recently, RC has also risen as a reasonable alternative to OC for MIBC. The objective of our retrospective study was to evaluate pathological Complete Response(pCR), the impact on disease-free survival (DFS), overall survival(OS), and toxicity adverse events of DD-MVAC treated with RC or OC. Methods: An institutional database of a total of 16 patients (pts) with MIBC was reviewed in an IRB approved fashion. Eligible pts were treated with peri-operative chemotherapy using DD-MVAC q 14 days for 3-4 cycles plus cystectomy between 04/2011 and 01/2014. DD-MVAC therapy consisted of 30 mg/m2methotrexate, cisplatin 70 mg/m2, doxorubicin 30 mg/m2 and vinblastine 3 mg/m2 on day 1 and pegylated GCSF 6 mg sq on day 2. The choice of either RC or OC was per surgeon’s discretion. Results: The average age was 63.5 years old. 10 pts received neo-adjuvant DD-MVAC and 2 patients received DD-MVAC post-operatively. 50% received 3 cycles DD-MVAC, 50% received 4 cycles. 58% of the cohort had T2 stage and 42% had T3 stage. 42% of the cohort underwent RC and 58% underwent OC. The average hospital stay in days was 5.6 for RC and 8.3 for OC. From the 10 pts who received neo-adjuvant DD-MVAC, 50% had a pCR. The DFS & OS were both 92%. The only patient who has progressed and died had micropapillary type histology. Grade 3 or 4 toxicities include: Anemia (25%), Fatigue (17%), Hypomagnesemia (8%). Conclusions: Although this is not a randomized study, peri-operative DD-MVAC plus cystectomy is very effective and well tolerated and may be associated with improved survival among patients with MIBC. The use of RC shorten the duration of hospital days and did not negatively impact on the OS or PFS. This data needs to be confirmed by randomized clinical trials.
Social connectivity and outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).
Authors: Andrew Fintel, OMER HASSAN JAMY, Jason Claud Chandler, Michael Gary Martin
Journal: Journal of Clinical Oncology (2014)

7049 Background: While the outcomes for AYAs with ALL are worse when treated on adult rather than pediatric protocols, one criticism is that this may be due to “emancipation” of young adults. Methods: Using case listing session of SEER 18 (1973-2010) we examined outcomes for AYAs with ALL defined similar to CALGB 10403 (age 18-30) predicated on marital and insurance status as surrogates of emancipation (limiting analysis to 2007-2010). Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the chi-squared test and log rank test (Mantel-Cox); all p-values were 2-sided. Results: While age (24 and younger versus 25 and older) was predictive of median OS (NR v 33; p=0.0029) (3-yr OS 66% v 49%); social factors were not as detailed in the Table; NR = not reached. Conclusions: Social connectivity, as defined by insurance status and marriage, did not influence outcomes for AYAs with ALL, arguing that intrinsic differences in disease and disease-specific therapies are more important than social issues. All Insured Uninsured P Married Single p # 576 503 73 112 464 Age 22 22 23 27 21 Ethnicity (W/B/O%) 85/6/9 85/6/9 84/11/5 92/2/6 83/7/10 Gender (M/F%) 64/36 64/36 67/33 63/37 64/36 Median year of Dx 2008 2008 2008 2008 2009 Subtype (%) B-cell ALL, NOS 5 4 6 7 5 Burkitt cell leukemia 2 2 4 2 2 Precursor cell lymphoblastic leukemia 80 80 82 81 80 T-cell leukemia/lymphoma 12 13 8 10 13 Median OS (m) NR NR 33 NR NR 3-yr OS % 57 61 50 0.2334 55 62 0.1084
Abstract 18857: Arterial Stiffness Relates to Worse Renal Function in Adults From the ELSA-Brasil Study
Authors: Julia S Candido, Luisa C Brant, Antonio L Ribeiro, Luana G Giatti, Paulo A Lotufo, Jose G Mill, Bruce B Duncan, Lidyane V Camelo, Sandhi M Barreto
Journal: Circulation (2017)

Background: Chronic kidney disease (CKD) is associated with a higher occurrence of cardiovascular diseases (CVD). Increased arterial stiffness predicts cardiovascular events independently of tradit...
Iberdomide (CC-220) Has Synergistic Anti-Tumor and Immunostimulatory Activity Against Multiple Myeloma in Combination with Both Bortezomib and Dexamethasone, or in Combination with Daratumumab in Vitro
Authors: Michael Amatangelo, Chad C. Bjorklund, Jian Kang, Ann Polonskaia, Sridevi Viswanatha, Anjan Thakurta
Journal: Blood (2018)
Reoperations After Bariatric Surgery in 26 Years of Follow-up of the Swedish Obese Subjects Study
Authors: Stephan Hjorth, Ingmar Näslund, Johanna C. Andersson-Assarsson, Per-Arne Svensson, Peter Jacobson, Markku Peltonen, Lena M. S. Carlsson
Journal: JAMA Surgery (2019)

Bariatric surgery is an established treatment for obesity, but knowledge on the long-term incidence of revisional surgery is scarce.To determine the incidence and type of revisional surgery after bariatric surgery in 26 years of follow-up of participants in the Swedish Obese Subjects (SOS) study.The SOS study is a prospective nonrandomized controlled study comparing bariatric surgery (banding, vertical banded gastroplasty [VBG], and gastric bypass [GBP]) with usual care. The bariatric surgeries in the SOS study were conducted at 25 public surgical departments in Sweden. Men with body mass index values of 34 or higher and women with body mass indexes of 38 or higher were recruited to the surgery group of the SOS study between September 1, 1987, and January 31, 2001, and follow-up continued until December 31, 2014. Data analysis occurred from November 2016 to April 2018.Banding, VBG, or GBP.Revisional surgeries, analyzed using data from questionnaires, hospital records, and the Swedish National Patient register through December 31, 2014.A total of 2010 participants underwent surgery. The age range was 37 to 60 years. A total of 376 participants underwent banding (18.7%), while 1365 had VBG (67.9%) and 266 had GBP (13.2%). During a median follow-up of 19 years, 559 participants (27.8%) underwent first-time revisional surgery, including 354 conversions to other bariatric procedures (17.6%), 114 corrective surgeries (5.6%), and 91 reversals to normal anatomy (4.5%). Revisional surgeries (conversions, corrective surgery, and reversals) were common after banding (153 of 376 [40.7%]) and VBG (386 of 1365 [28.3%]) but relatively rare after GBP (20 of 266 [7.5%]). Patients who had banding and VBG primarily underwent conversions to GBP or reversals. Incidence of reversals was 5 times higher after banding than after VBG (40.7% vs 7.5%; unadjusted hazard ratio, 5.19 [95% CI, 3.43-7.87]; P < .001). Corrective surgeries were equally common irrespective of the index surgery (72 of 1365 patients who had VBG [5.3%]; 23 of 376 patients who had banding [6.1%]; 19 of 266 patients who had GBP [7.1%]). Revisional surgery indications, including inadequate weight loss, band-associated complications (migration, stenosis, and slippage), staple-line disruptions, and postsurgical morbidity, varied depending on index surgery subgroup. Most corrections occurred within the first 10 years, whereas conversions and reversals occurred over the entire follow-up period.Corrective surgeries occur mainly within the first 10 years and with similar incidences across all 3 surgical subgroups, but indications varied. Conversions (mainly to GBP) and reversals occurred after many years and were most frequent after banding and VBG, reflecting a higher overall revisional surgery demand after these operations.
Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial
Authors: Silvia Dellapasqua, Kathryn P. Gray, Elisabetta Munzone, Daniela Rubino, Lorenzo Gianni, Harriet Johansson, Giuseppe Viale, Karin Ribi, Jürg Bernhard, Roswitha Kammler, Rudolf Maibach, Manuela Rabaglio-Poretti, Barbara Ruepp, Angelo Di Leo, Alan S. Coates, Richard D. Gelber, Meredith M. Regan, Aron Goldhirsch, Marco Colleoni
Journal: Journal of Clinical Oncology (2018)

PURPOSE To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer. PATIENTS AND METHODS Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2–negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.5 mg/day for six 28-day cycles. Surgery was performed 2 to 3 weeks after the last injection. Serum was collected at baseline, after 24 and 72 hours, at 7 and 14 days, and then before injections on cycles 2 through 6. The primary end point was time to optimal OFS (time from the first injection to first assessment of centrally assessed estradiol level ≤ 2.72 pg/mL [≤ 10 pmol/L] during neoadjuvant therapy). The trial had 90% power to detect a difference using a log-rank test with a two-sided α of .05. Secondary end points included response, tolerability, and patient-reported endocrine symptoms. RESULTS Between February 2014 and January 2017, 51 patients were enrolled (n = 26 received triptorelin plus letrozole; n = 25 received degarelix plus letrozole). Time to optimal OFS was three times faster for patients assigned to degarelix and letrozole than to triptorelin and letrozole (median, 3 v 14 days; hazard ratio, 3.05; 95% CI, 1.65 to 5.65; P &lt; .001). Furthermore, OFS was maintained during subsequent cycles for all patients assigned to receive degarelix and letrozole, whereas 15.4% of patients assigned to receive triptorelin and letrozole had suboptimal OFS after cycle 1 (six events during 127 measurements). Adverse events as a result of both degarelix plus letrozole and triptorelin plus letrozole were as expected. CONCLUSION In premenopausal women receiving letrozole for neoadjuvant endocrine therapy, OFS was achieved more quickly and maintained more effectively with degarelix than with triptorelin.
Retraction Note: LAMP2 expression dictates azacytidine response and prognosis in MDS/AML
Authors: Alix Dubois, Nathan Furstoss, Anne Calleja, Marwa Zerhouni, Thomas Cluzeau, Coline Savy, Sandrine Marchetti, Mohamed Amine Hamouda, Sonia Boulakirba, François Orange, Sandra Lacas-Gervais, Jean-Michel Karsenti, Nicolas Mounier, Jérôme Tamburini, Alexandre Puissant, Frederic Luciano, Arnaud Jacquel, Patrick Auberger, Guillaume Robert
Journal: Leukemia (2020)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Abstract 18012: Modeling of a Rare SCN10A Variant (A1886V) Linked with Early-Onset Atrial Fibrillation Shortens Atrial Action Potential Duration
Authors: Robert L Abraham, Eleonora Savio-Galimberti, Tao Yang, Dan M Roden, Dawood Darbar
Journal: Circulation (2014)

Introduction: SCN10A encodes the tetrodotoxin-resistant sodium channel isoform Nav1.8, which is variably expressed in neuronal tissue and heart and has been associated with atrial fibrillation (AF). We resequenced the SCN10A gene in 274 early-onset AF probands and identified a rare non-synonymous variant (A1886V) that co-segregated with AF in a kindred. In-vitro electrophysiological studies revealed that this variant displayed a “gain-of-function” phenotype with increased peak (INa-peak) and late (INa-L) sodium currents. Hypothesis: Here, we hypothesized that the increased peak and late INa associated with A1886V variant might modulate atrial action potential duration (APD) and thus increase susceptibility to AF. Methods: We used 2 Clancy-Rudy INa Markov models modified to fit wild-type (WT) and A1886V variant. Modeled currents were incorporated into the Courtemanche-Ramirez-Nattel model of human atrial AP. The overall SCN10A/Nav1.8 contribution to the total INa was simulated in the 5-50% range of WT-SCN5A/Nav1.5 current, and for each overall SCN10A magnitude, the contribution of A1886V compared to WT was simulated in the 0-to-100% range. Cycle-length used was 1000 ms (frequency 1 Hz). Results: While the precise magnitude of SCN10A atrial expression (WT and A1886V) has not yet been determined, simulation of a range of contributions of each component to atrial AP demonstrated incremental morphology changes with removal of the “spike and dome” and triangularization of AP associated with progressive shortening of APD90 (301 ms at 0% SCN10A contribution; 281 ms at 10% SCN10A [100% WT, 0% A1886V]; 261 ms at 10% SCN10A [0% WT, 100% A1886V]) (Table). Conclusion: Computational modeling of A1886V-SCN10A rare variant linked with familial AF surprisingly shortened atrial APD by removal of phase 1 “spike and dome” and augmentation of atrial AP “triangularization”, providing a potential mechanism for increased AF susceptibility.
Abstract 227: The Acceptability and Impact of a Pilot Community Hands-Only Cardiopulmonary Resuscitation Training Program in India
Authors: Brent V Martinez, Radhika Chimata, Nishi Dedania, Shaveta Khosla, Stockton Mayer, Vemuri Murthy, Vijay Yeldandi
Journal: Circulation (2018)

Background: Sudden Cardiac Arrest (SCA) is a leading cause of global mortality. In India, 700,000 people die from SCA annually, many of which are under the age of 50. Immediate bystander CPR improves chances of survival, however, CPR education and training are difficult in a developing country such as India. In collaboration with University of Illinois Global Health Program, the Indian American Medical Association (Illinois), SHARE INDIA, and the American Heart Association we studied native rural Indian populations, hoping to enhance CPR education and skills training. This is the first rural community CPR project in India involving a university residency-training program from the USA. Methods: We conducted hands-only CPR training (based on the latest AHA guidelines) in the Telangana State in India, recruiting 582 participants with the help of local health outreach workers. A pre-training survey was used to assess baseline knowledge and impressions of CPR. This was followed by training in hands-only CPR consisting of an oral presentation followed by interactive CPR manikin training. A post-course survey was conducted after training. Chi square test and McNemar’s test were used for the analysis of data using SAS. Results: Of 582 participants, 65% were males and the mean age was 19.4 + 5.9. Gender was not associated with pre/post-test CPR knowledge, comfort with CPR, or belief in CPR efficacy. However, in paired analysis, there were significant differences (p&lt;0.0001) in all knowledge and perception measures from pre-to-post training. While only 6% knew the correct compression rate pre-training, 96% knew the correct answer post-training (4% vs. 94% in females, 6% vs. 96% in males). Similar results were seen for the compression depth variable. Training also improved comfort level in performing CPR (64% vs. 87% in females and 70% vs. 89% in males) and belief that CPR can save lives (49% vs. 96% in females and 51% vs. 97% in males). Conclusions: The program was successful in enhancing knowledge, comfort, and perceptions of CPR. Given the high prevalence of SCA in India, training the public in hands-only CPR can be a cost-effective care strategy in resource-limited areas. Due to the success of this pilot, we are planning to continue the program.
Defining the neuroendocrine tumors landscape: A 15-year population-based analysis of incidence, outcomes, and therapies.
Authors: Julie I. Hallet, Calvin Law, Ning Liu, Refik Saskin, Simron Singh
Journal: Journal of Clinical Oncology (2014)

4114 Background: Neuroendocrine Tumors (NETs) are poorly understood malignancies. We sought to define epidemiologic characteristics and outcomes, and describe systemic, interventional and surgical therapies use for NETs. Methods: We conducted a population-based retrospective cohort study of all adult patients with NETs in Ontario from 1994 to 2009, linking propsective databases linked at the Institute of Clinical Evaluative Sciences. We looked at incidence, proportion of metastatic disease, overall survival (OS), and use of systemic therapy (ST), liver embolization (LE), and surgery. Results: We identified 5619 NET cases. Incidence of NETs increased from 2.48 to 5.86 per 100 000 per year over 15 years. Synchronous metastases were found in 20.8% and metachronous metastases in 38%. Incidence and metastases varied according to primary NET site. Around time of diagnosis (60 days pre/post diagnosis), 56.8% did not consult a surgeon and 97.2% did not see a medical oncologist. Initial primary site resection was performed in 63.9% broncho-pulomnary (BP), 57.1% gastrointestinal (GI) and 46.4% pancreas (PA) NETs (p <0.001). 53.7% of all liver metastases were resected. ST was used in 46% of PA, 23.2% GI and 25.4% BP NETs, and LE in 8.1% BP, 11.9% GI, and 19.2% PA NETs. 10-year OS was 42.8%, with independent predictors of worse OS being: advanced age, male gender, low socioeconomic status, rural living, and pancreas and small intestine sites. Conclusions: NETs incidence has markedly increased over 15 years, with outcomes disparities based on demographics, social, and tumor characteristics. Patterns of care for NETs were irregular and sporadic. Numerous NETs were not assessed by a surgeon or medical oncologist, indicating worrisome potential under treatment and non-optimal management. Future work is needed to define mechanisms explaining this portrait in order to improve outcomes through early diagnosis, more frequent surgical referrals and standardization of therapies.
Outcomes of patients with late relapse metastatic renal cell carcinoma treated with targeted therapies.
Authors: Kamal Kishore Mandalapu, Marc Ryan Matrana, Teja Poosarla
Journal: Journal of Clinical Oncology (2014)

e15579 Background: Approximately 20- 30 % of the patients (pts) with renal cell carcinoma (RCC) develop recurrence after treatment of localized disease. Of these pts, the great majority recur within the first few years following surgery. Rarely, late recurrences (LRs) are seen after >5 years of disease free survival. Targeted therapies (TT) have improved the outcome in patients (pts) with metastatic renal cell carcinoma (mRCC). Little data is available about outcomes of mRCC pts with LR treated with TT. Methods: We reviewed records of consecutive pts with mRCC who had LR >5 years and were treated with TT between 11/1/2006 and 11/1/2013. Outcomes were tabulated using basic statistical techniques. Adverse Events (AEs) were graded using CTCAE v4.0 Results: 25 pts (median age 69 years, 84% male, 100% clear-cell, all with prior nephrectomies) met inclusion criteria with LR>5 years. 16% had Karnofsky PS<80%. 76% had good-risk disease and 24% had intermediate-risk by MSKCC criteria at time of diagnosis with recurrent disease. 11 pts died. Median OS for all pts from the time of recurrence is 27.9 mos (range 6.7 – 129 mos). The 3 year OS rate from time of recurrence was 52%. The median number of sequential TT received was 2 (range 1-4). Median time on first line TT was 20.7 months; median time on all TT was 35.1 months. 41% of pts received pazopanib in the frontline setting, 26% received sunitnib, 26% received sorafenib and 7% received other TT. 68% received TT in the second-line and subsequent settings. Common AEs of TT included fatigue (52%), diarrhea (36%), hypertension (36%), anorexia (28%), hair and skin changes (24%), increased LFTs (20%), nausea/vomiting (16%), and 95% of AEs were grade 1/2. Conclusions: In this retrospective study, the outcomes of mRCC pts with LR treated with TT appears improved. Pts had overall survival compared to historical controls, but total time on TT and three year OS rate were prolonged. AEs were mild/moderate and manageable. Outcome data on different sequences of TT will be provided at meeting presentation.
Impact of dose intensity of XELOX and MFOLFOX6 on survival of metastatic colorectal cancer patients: A retrospective analysis at the Jewish General Hospital between 2006 and 2013.
Authors: Aline Mamo, Tomas Kavan, Young Soo Rho, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2014)

e14584 Background: XELOX for colorectal cancer (CRC) reportedly causes more grade III/IV toxicity in clinical practice, leading to a greater reduction in dose intensity than mFOLFOX6. We reported that in the metastatic setting, 75% of XELOX-treated patients received a lower dose up front compared to 33% of mFOLFOX6-treated patients. Further dose reductions occurred in 31% of XELOX-treated patients compared to 20% of mFOLFOX6-treated patients. Treatment delays occurred in 43% of XELOX and 60% of mFOLFOX6-treated patients due to grade III/IV toxicities. This suggested that the higher dose reduction of XELOX compared to mFOLFOX6 facilitated treatment completion with less toxicities. Objective: To investigate the impact of reduced dose intensity on progression free survival (PFS) and overall survival (OS) of stage IV CRC patients treated with XELOX or mFOLFOX6. Methods: A chart review was conducted on 107 patients with stage IV CRC treated with XELOX or mFOLFOX6 from 2006 to 2013 at the Jewish General Hospital. The primary endpoints were PFS and OS analyzed using the Kaplan-Meier method. Results: Sixty-five patients (61%) received XELOX over a mean of 24.9 weeks (median age 66 years, 71% males, 74% colon, 97% ECOG 0-1, 47/65 post resection) and 42 patients (39%) received mFOLFOX6 over a mean of 26.1 weeks (median age 62 years, 60% males, 55% colon, 91% ECOG 0-1; 17/42 post resection). Bevacizumab, given in combination with XELOX (30/65; 46%) or mFOLFOX6 (29/42; 60%), did not increase the incidence of bleeding or hypertension in either group. Clinically, there appeared to be no difference in median PFS 25 months (95% CI: 18-40) and OS 40 months (95% CI: 25-49) in XELOX-treated patients compared to median PFS 18 months (95% CI: 12-NA) and OS 32 months (95% CI: 15-35.5) in mFOLFOX6-treated patients. No statistical difference was seen in OS (p = 0.0949). Conclusions: Our results suggest that clinically reduced dose intensity of XELOX does not affect PFS and OS in metastatic CRC patients compared to mFOLFOX6. Future studies should consider treatment costs and efficacy, when determining the appropriate choice of treatment for metastatic CRC patients.