tbuckley/cabot-search huggingface dataset:
Impact of postoperative complications on oncologic outcomes after rectal cancer surgery: An analysis of the United States Rectal Cancer Consortium.
Authors: Adriana C. Gamboa, Rachel M. Lee, Michael K. Turgeon, Christopher Varlamos, Scott E. Regenbogen, Katherine Hrebinko, Jennifer Holder-Murray, Jason T. Wiseman, Aslam Ejaz, Michael P. Feng, Alexander Hawkins, Philip Bauer, Matthew Silviera, Shishir K. Maithel, Glen C. Balch
Journal: Journal of Clinical Oncology (2020)

41 Background: Postoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not known. Methods: The US Rectal Cancer Consortium (2007-17) was reviewed for patients with primary rectal adenocarcinoma who underwent R0/R1 low anterior resection (LAR) or abdominoperineal resection (APR). 90-day POCs were categorized as major vs minor and grouped into infectious, cardiopulmonary (CP), thromboembolic (TE), renal, or intestinal dysmotility. Primary outcomes were 5-yr overall survival (OS) and recurrence-free survival (RFS). Results: Of 1136 pts, median age was 59 yrs (IQR 51-67), 61% were male (n = 693), median f/u was 31 mos (IQR 13-54). 70% underwent LAR (n = 799) and 30% APR (n = 337). Complication rate was 46% (n = 527), with 63% minor (n = 330) and 32% major (n = 170). Of all POCs, infectious complications comprised 20% (n = 105), cardiopulmonary 3% (n = 14), thromboembolic 5% (n = 25), renal 9% (n = 46) and intestinal dysmotility 19% (n = 100). When compared to minor or no POCs, major POCs were associated with both worse RFS (48 vs 63 vs 76% p &lt; 0.01) and OS (64 vs 76 vs 80% p &lt; 0.01). While a single POC was associated with worse RFS (61 vs 76% p &lt; 0.01), multiple POCs were associated with worse OS (62% vs 79% p = 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (56 vs 76% p &lt; 0.01) while CP and TE POCs were associated with worse OS (CP 40 vs 78% p &lt; 0.01; TE 63 vs 78% p &lt; 0.01). Postoperative renal dysfunction was associated with both worse RFS (26 vs 76%, p &lt; 0.001) and OS (62 vs 78% p = 0.01). This persisted on MV analysis for OS when accounting for pathologic stage, receipt of neoadjuvant therapy, and final margin status (CP: HR 3.6 p = 0.01; TE: HR 19.4 p &lt; 0.01; renal: HR 2.4 p = 0.01) and for RFS (infectious: HR 2.1 p &lt; 0.01; renal: HR 3.2 p &lt; 0.01). Conclusions: Major complications after proctectomy for cancer are associated with decreased recurrence-free and overall survival. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.
The benefits of upfront primary tumor resection for metastatic small bowel neuroendocrine tumors: A population-based analysis.
Authors: Sean Bennett, Natalie Coburn, Calvin Law, Victoria Zuk, Alyson Mahar, Simron Singh, Sten Myrehaug, Haoyu Zhao, Laura E Davis, Vaibhav Gupta, Julie Hallet
Journal: Journal of Clinical Oncology (2020)

620 Background: Early resection of the primary tumor in metastatic small bowel neuroendocrine (SB-NET) remains controversial. Conflicting data exist regarding its clinical and survival benefits. We compared the long-term outcomes of upfront small bowel resection (USBR) and non-operative management (NOM) for metastatic SB-NETs. Methods: A population-based analysis of patients with SB-NET metastatic at diagnosis between 2001-2017 was conducted by linking administrative datasets. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel related surgery. Secondary outcome was overall survival (OS). USBR and NOM patients were matched 2:1 using a propensity-score including age, sex, year of diagnosis, socioeconomic status, institution academic status, and functional status. We used time-to-event analyses with cumulative incidence functions and univariate Andersen-Gill regression for primary outcomes, and Kaplan-Meier methods and univariate Cox regression for OS. E-value methods assessed the potential for residual confounding. Results: Of 1000 patients identified, 785 (78.5%) had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Matched groups were well balanced with standardized mean differences &lt;10% for matched variables. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, p&lt;0.001) than those with NOM, with hazard ratio (HR) 0.72 (95%CI 0.57-0.91). USBR was associated with lower risk of subsequent small bowel related surgery (15.4% vs 40.3%, p&lt;0.001), with HR 0.41 (95%CI 0.30-0.56). OS was superior for USBR patients compared to NOM (HR 0.55, 95%CI 0.41-0.74). E-values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. Conclusions: USBR for metastatic SB-NETs was associated with clinical benefits over NOM, in terms of decreased subsequent admissions and interventions, and improved survival. USBR should be considered for metastatic SB-NETs to improve patient outcomes.
Immune-related adverse events and efficacy outcomes in patients treated with immunotherapy: A systematic review and meta-analysis.
Authors: Eric Druyts, Mark Boye, Himani Agg, Catherine Muehlenbein, Andrew Frederickson, Theresa Bayt
Journal: Journal of Clinical Oncology (2020)

92 Background: Immunotherapy (IO) can lead to immune-related adverse events (irAEs). Evidence on the association of irAEs and efficacy is limited. Methods: We conducted a systematic review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (inception to July 1, 2019) to identify randomized controlled trials (RCTs) reporting irAEs, incidence and efficacy data for pembrolizumab (PEM), nivolumab (NIVO), ipilimumab (IPI), atezolizumab, avelumab, durvalumab, and aldesleukin in lung, renal, head and neck cancer, and melanomas. RCTs assessing IO monotherapy or IO combinations in at least one arm were included. Evaluated outcomes were 1) irAE incidence (rash, pruritis, diarrhea, colitis, hypothyroidism, hyperthyroidism, transaminitis, hypophysitis, pneumonitis, arthralgia, anemia, and hepatitis); and 2) efficacy (response and survival). irAE incidence data will be pooled and meta-analysis performed to assess the association of irAEs with efficacy; heterogeneity between RCTs will be evaluated. Results: Fifty RCTs were included: IOs were compared to chemotherapy or chemotherapy-combinations (19), to other interventions (8), to placebo (3), and head-to-head (20). irAE reporting and definitions were heterogeneous across RCTs. The most common all-grade irAEs were skin, GI, and endocrine. For skin irAEs, rash ranged from 0% (PEM 2 mg/kg, n = 6) to 73% (NIVO + IPI, n = 11); pruritus was from 1% (PEM 2 mg/kg, n = 89) to 50% (NIVO + IPI, n = 6). For GI irAEs, diarrhea ranged from 0% (PEM 2 mg/kg, n = 6) to 64% (NIVO + IPI, n = 11); colitis was from 0% (NIVO 3 mg/kg, n = 98) to 23% (NIVO + IPI, n = 94). For endocrine irAEs, hypothyroidism ranged from 0% (NIVO 3 mg/kg, n = 12) to 83% (NIVO + IPI, n = 6), hyperthyroidism was from 0% (PEM 2 mg/kg, n = 6 and IPI 3 mg/kg, n = 46) to 27% (NIVO + IPI, n = 11), and hypophysitis was from 0% (PEM 10 mg/kg, n = 84 and NIVO 3 mg/kg, n = 25) to 26% (NIVO + IPI, n = 35). Liver, pulmonary, and musculoskeletal irAEs, and anemia, were reported less frequently and with lower incidence. Conclusions: irAEs are increasingly reported in IO RCTs, but lack reporting and definition consistency. The meta-analysis results may provide clarity on irAEs incidence and association with efficacy.
Abstract 14091: Decreased Blood Platelet Count and Serum Level of Cholesterol Reflects the Functional Deterioration of Advanced Fontan Associated Liver Disease
Authors: Chun Wei Lu, Chih Horng Wu, Miao Tzu Huang, Chee Seng Lee, Ming Tai Lin, Shuenn Nan Chiu, Chun An Chen, Jou Kou Wang, Mei Hwan Wu
Journal: Circulation (2019)

Introduction: Late hepatic complications such as liver fibrosis or cirrhosis are increasingly described in patients with Fontan circulation. Clinical evaluation of Fontan associated liver disease h...
Altruism <i>in Extremis</i> — The Evolving Ethics of Organ Donation
Authors: Lisa Rosenbaum
Journal: New England Journal of Medicine (2020)

Interview with Dr. Joshua Mezrich on the dead-donor rule and how it affects donation of organs in the United States and Canada. (12:34)Download With a clear understanding of his terminal prognosis, W.B. wanted to donate his organs before he died — but the legal and ethical hurdles proved insurmountable. In Canada, where medical assistance in dying is now legal, some patients are able to fulfill this last wish.
Extensive Shifts from <i>Cis</i>- to <i>Trans</i>-splicing of Gymnosperm Mitochondrial Introns
Authors: Wenhu Guo, Andan Zhu, Weishu Fan, Robert P Adams, Jeffrey P Mower
Journal: Molecular Biology and Evolution (2020)

Abstract Hundreds of plant mitogenomes have been sequenced from angiosperms, but relatively few mitogenomes are available from its sister lineage, gymnosperms. To examine mitogenomic diversity among extant gymnosperms, we generated draft mitogenomes from 11 diverse species and compared them with four previously published mitogenomes. Examined mitogenomes from Pinaceae and cycads retained all 41 protein genes and 26 introns present in the common ancestor of seed plants, whereas gnetophyte and cupressophyte mitogenomes experienced extensive gene and intron loss. In Pinaceae and cupressophyte mitogenomes, an unprecedented number of exons are distantly dispersed, requiring trans-splicing of 50–70% of mitochondrial introns to generate mature transcripts. RNAseq data confirm trans-splicing of these dispersed exons in Pinus. The prevalence of trans-splicing in vascular plant lineages with recombinogenic mitogenomes suggests that genomic rearrangement is the primary cause of shifts from cis- to trans-splicing in plant mitochondria.
Abstract 15657: Celular Senescence and Vitamin E Intake in Cardiovascular Disease Patients: The Cordioprev Study
Authors: Andreea Corina, Oriol Rangel-Zuñiga, Ana Leon-Acuña, Rosa Jimenez-Lucena, Gracia Quintana-Navarro, Javier Lopez-Moreno, Javier Delgado-Lista, Jose Lopez-Miranda, Pablo Perez-Martinez
Journal: Circulation (2018)

Introduction: It has been previously described that there is an association between cardiovascular disease and an accelerate biological aging. Leukocyte telomere length (LTL) is a biomarker of cell...
Palliative Care for Family Caregivers
Authors: Sorayya Alam, Breffni Hannon, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2020)

Family caregivers provide substantial care for patients with advanced cancer, while suffering from hidden morbidity and unmet needs. The objectives of this review were to examine risk factors associated with caregiving for patients with advanced cancer, evaluate the evidence for pertinent interventions, and provide a practical framework for palliative care of caregivers in oncology settings. We reviewed studies examining the association of factors at the level of the caregiver, patient, caregiver-patient relationship, and caregiving itself, with adverse outcomes. In addition, we reviewed randomized controlled trials of interventions targeting the caregiver, the caregiver-patient dyad, or the patient and their family. Risk factors for adverse mental health outcomes included those related to the patient’s declining status, symptom distress, and poor prognostic understanding; risk factors for adverse bereavement outcomes included unfavorable circumstances of the patient’s death. Among the 16 randomized trials, the most promising results showed improvement of depression resulting from early palliative care interventions; results for quality of life were generally nonsignificant or showed an effect only on some subscales. Caregiving outcomes included burden, appraisal, and competence, among others, and showed mixed findings. Only three trials measured bereavement outcomes, with mostly nonsignificant results. On the basis of existent literature and our clinical experience, we propose the CARES framework to guide care for caregivers in oncology settings: Considering caregivers as part of the unit of care, Assessing the caregiver’s situation and needs, Referring to appropriate services and resources, Educating about practical aspects of caregiving, and Supporting caregivers through bereavement. Additional trials are needed that are powered specifically for caregiver outcomes, use measures validated for advanced cancer caregivers, and test real-world interventions.
Antioxidant Vitamins for Cataracts: 15-Year Follow-up of a Randomized Trial
Authors: Muthiah Srinivasan, Ravilla Duraisami Ravindran, Kieran S. O’Brien, Usha R. Kim, John H. Wilkins, John P. Whitcher, Thomas M. Lietman, David C. Gritz, Jeremy D. Keenan
Journal: Ophthalmology (2020)
Senior resident versus fellow participation during complex cancer operations.
Authors: Susanna W. L. de Geus, Gyulnara G Kasumova, Mariam F. Eskander, Sing Chau Ng, David B. McAneny, Jennifer F. Tseng, Teviah E. Sachs
Journal: Journal of Clinical Oncology (2020)

330 Background: Teaching hospitals that train both general surgery residents and fellows in complex general surgical oncology have become more common. Despite ACGME dictums, attending surgeons may favor either residents or fellows assisting on operations of greater complexity, depending upon a variety of factors, including local surgical culture. This study investigates whether participation of a senior resident versus a fellow impacts outcomes of complex cancer surgery. Methods: Patients who underwent esophagectomy, or gastrectomy with assistance from either a senior resident (PGY-4 or 5) or a fellow (PGY-6 to 8) were identified from the American College of Surgeon’s National Surgical Quality Improvement Program (2007-2012). Analyses were performed separately for each operation. Propensity-scores were created for the odds of undergoing the operation assisted by a fellow. Patients were matched based on propensity score, and outcomes were compared after matching. Results: In total, 1,160 esophagectomies and 2,432 gastrectomies were identified. Senior resident participation was reported in 60.2% and 86.6%, respectively. Resident involvement was associated with non-white race (17.0% vs. 13.8%; p &lt; 0.001), and lower rates of neoadjuvant chemotherapy (6.4% vs. 11.7%; p &lt; 0.001). After matching, rates major complication rates were slightly higher for patients who underwent esophagectomies involving a resident compared to fellow (38.1% vs. 31.8%; p = 0.0447). However, major complications rates were similar for gastrectomy (21.2% vs. 22.1%; p = 0.775). In addition, operative time was shorter for gastrectomy (212 vs. 232 min; p = 0.009) involving a resident compared to a fellow, but comparable for patients who underwent esophagectomy (327 vs. 337 min; p = 0.310). Conclusions: The results of this study suggest that senior resident participation in complex cancer operations does not negatively impact operative time or outcomes, compared to involvement of a surgical oncology fellow. Although confounding by operative autonomy may exist, these findings indicate that senior residents should be given the same opportunities as fellows to participate in these potentially more challenging operations.
HIPAA in the Era of Data Sharing—Reply
Authors: I. Glenn Cohen, Michelle M. Mello
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prospective study with circulating tumor cells as potential prognosis biomarker in metastatic colorectal cancer.
Authors: Virgilio Souza E Silva, Emne Ali Abdallah, Celso Abdon Lopes de Mello, Milena Shizue Tariki, Vinicius Fernando Calsavara, Ludmilla T.D. Chinen
Journal: Journal of Clinical Oncology (2020)

203 Background: Colorectal cancer (CRC) is one of the most common cancer worldwide. Around 30% present metastatic disease at diagnosis and 50%–60% of patients develop metastasis. New prognostic markers are needed and circulating tumor cells (CTCs) are a promising tool. Methods: Prospective study conducted by blood collection from 75 patients (pts) with metastatic CRC (mCRC), twice, with 2 months interval, together with image exams for therapeutic response evaluation. CTCs were detected by ISET and identified by immunocytochemistry. Results: The mean age was 57.3 years old (24-81). RAS mutations in primary tumor was found in 38% (19/50) of patients (pts) and left colon topography in 41.3% (31/75). Comparing the baseline CTC level (CTC1) with the level at first follow-up (CTC 2), pts with CTC2 – CTC1 &gt; 5.5 per ml demonstrated poor progression-free survival (PFS) (3.2 months) when compared to CTC 2 – CTC1 ≤ 5.5 (9.1 months) (p= 0.005). The median overall survival (OS) was 24.5 months for pts with CTC 1 &gt; 1.5 per ml and 34.2 months for those with CTC1 ≤ 1.5 per (HR=1.89, 95% CI, 1.01 to 3.52; p= 0.041). Patients with RAS mutation (P= 0.001), primary tumor in the right colon (p= 0.014) and expression of Multidrug Resistance Protein 1 in CTCs (p= 0.044) had worse OS. By multivariable analyses, CTC 1 &gt; 1.5/mL (p= 0.025) was an independent prognostic factor. Conclusions: This prospective study confirmed that counts of CTCs at baseline (CTC1) is an important prognostic marker for monitoring mCRC and correlates with other established prognostic factors. Clinical trial information: NCT02979470.
An exploratory study of metformin (Met) with or without rapamycin (Rapa) as maintenance therapy after induction chemotherapy in patients (Pts) with metastatic pancreatic adenocarcinoma (PDA).
Authors: Katherine M. Bever, Erkut Hasan Borazanci, Elizabeth Thompson, Annie Wu, Jennifer N. Durham, Meizheng Liu, Cara Wilt, Wei Fu, Jeffrey P. Leal, Ana De Jesus-Acosta, Hao Wang, David Cosgrove, Lei Zheng, Daniel A. Laheru, Daniel D. Von Hoff, Elizabeth M. Jaffee, Jonathan Powell, Dung T. Le
Journal: Journal of Clinical Oncology (2020)

700 Background: Few studies have examined maintenance therapy in unselected pts with metastatic PDA (mPDA). mTOR signaling is central to several oncogenic pathways in PDA and also has a role in T cell differentiation and activation, and we hypothesized a role for mTOR inhibition (mTORi) in the maintenance setting. Methods: This was a randomized open-label study conducted at 2 sites. Eligible pts had mPDA with stable disease for ≥6 months on chemotherapy and ECOG PS 0/1. Pts were randomized 1:1 to Met 850mg BID alone (Arm A) or with Rapa 4mg daily (Arm B), stratified by prior FOLFIRINOX. Baseline and on-treatment PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses. Results: 23 pts were randomized. Median age was 64 (range 34-77) and 82% had ECOG PS 1. 12 of 23 received prior FOLFIRINOX; 8 received &gt;1 prior line of therapy. 22 subjects (11 per arm) were treated per protocol. Treatment related adverse events of Grade ≥3 were seen in 0% vs 27% of pts in Arm A vs B and were all asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Median PFS/OS were 3.5 (95% CI: 2.9-9.2)/13.2 mos (95% CI: 7.8 to not reached) respectively, with 2 yr OS rate of 37% (95% CI: 21-66%); there were no differences between treatment arms. As expected in the maximally debulked setting, no responses were observed by RECIST; however, decreases in FDG avidity and/or CA199 were observed in several long-term survivors. Better survival was associated with low baseline neutrophil to lymphocyte ratio, baseline lack of assessable disease by PET, and with expansion of dendritic cells following treatment. Compared to Met alone, Met + Rapa was associated with decreased mTOR activity on some immune cell subsets and decreased metabolic fitness, but this was not correlated with outcome. Conclusions: Met +/- rapa maintenance for mPDA was well-tolerated and several pts achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of mTORi in the maintenance setting and to enhance pt selection for such approaches. Clinical trial information: NCT02048384.
Major impact of personalized dosimetry using 90Y loaded glass microspheres SIRT in HCC: Final overall survival analysis of a multicenter randomized phase II study (DOSISPHERE-01).
Authors: Etienne Garin, Lambros Tzelikas, Boris Guiu, Julia Chalaye, Julien Edeline, Thierry De Baere, Vania Tacher, Corentin Robert, Eric Assenat, Marie Terroir-Cassou-Mounat, Hélène Regnault, Xavier Palard, Sophie Laffont, Boris Campillo-Gimenez, Yann Rolland
Journal: Journal of Clinical Oncology (2020)

516 Background: 90Y loaded microsphere SIRT (radioembolization) is a treatment option in advanced HCC. However, no personalized dosimetric endpoints are currently used. The goal of this study was to compare the efficacy of 90Y loaded glass microsphere SIRT in HCC using a standard versus a personalized dosimetric approach. Methods: DOSISPHERE-01 was a multicenter, randomized phase 2 trial in unresectable HCC patients with at least one tumor ≥7cm. Treatment arm was randomly assigned (1:1) to standard dosimetry arm (SDA), with a goal to deliver 120±20Gy to the treated volume or to personalized dosimetry arm (PDA) with a goal to deliver at least 205Gy to the index lesion. The primary endpoint was the response rate (RR) of the index lesion according to EASL criteria. Secondary endpoints included dose response evaluation, safety and overall survival (OS). Results: Sixty HCC patients were randomized (PDA 31, SDA 29, intent to treat population-ITTP-), and 56 treated (28 in each arm). RR was significantly increased in the PDA versus the SDA, in the ITTP, respectively 64.5% versus 31% (p=0.0095) as in the safety population -SP- (treatment effectively received, personalized 35, standard 21), respectively 74.3% versus 14.3% (p&lt;0.0001). Median OS was significantly increased in the PDA versus the SDA, in the ITTP, respectively 26.7m (CI 95%:11.7-NR) versus 10.6m (CI 95%:6-16.8), p=0.0096, HR=0.421 (95%CI:0.215-0.826), p=0.0119, as in the SP, respectively 26.7m (CI 95%:11.7- NR) versus 9.5m (CI 95%:4.8-14.9), p=0.0015, HR=0.342 (95%CI:0.171-0.683), p=0.0023. Median OS was 26.7m (CI 95%:13.5-NR) versus 6.0m (CI 95%:3.8-14.9) for the patients who received a tumor dose ≥205 Gy or &lt;205 Gy respectively, p=0.0106, HR=0.336 (95%CI:0.154-0.735), p=0.0063. Treatment-related clinically relevant hepatic ≥grade 3 AEs were observed in 5.7% and 14.2% of the patients of the PDA and SDA arms, respectively, (p=ns). Conclusions: MAA SPECT/CT based personalized dosimetry is safe and dramatically increased RR and OS of HCC patients. These results question the interpretation of all phase 3 trials of SIRT designed without personalized dosimetry in HCC. Clinical trial information: 2015-A00894-45.