tbuckley/cabot-search huggingface dataset:
Correlation of surgeon radiology assessment with laparoscopic scoring in patients with advanced-stage ovarian cancer.
Authors: Nicole D. Fleming, Shannon Neville Westin, Larissa Meyer, Jose Alejandro Rauh-Hain, Aaron Shafer, Michaela Onstad, Lauren Patterson Cobb, Michael W. Bevers, Jennifer K. Burzawa, Behrouz Zand, Bryan M. Fellman, Amir A. Jazaeri, Charles F. Levenback, Robert L. Coleman, Pamela T. Soliman, Anil K Sood
Journal: Journal of Clinical Oncology (2019)

5570 Background: To determine the correlation between surgeon radiology assessment and laparoscopic scoring in patients with newly diagnosed advanced stage ovarian cancer. Methods: Following IRB approval, 14 gynecologic oncologists from a single institution performed a blinded review of radiology imaging from 20 patients with advanced stage ovarian cancer. All patients previously underwent laparoscopic scoring assessment to determine primary resectability at tumor reductive surgery (TRS) using a validated scoring method from April 2013 to December 2017. The patients with predictive index value (PIV) scores &lt; 8 were offered primary surgery and those with a score ≥8 received neoadjuvant chemotherapy (NACT). Surgeons viewed contrasted CT imaging reports and images from all patients in a blinded fashion and recorded PIV scores using the same validated scoring method. Linear mixed models were conducted to calculate the correlation between radiology and laparoscopic score for each surgeon and as a group. Once the model was fit, the inter-class correlation (ICC) and 95% confidence interval was calculated. Results: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Most patients had stage IIIC disease (85%) and median laparoscopic score was 9 (range 0-14). Surgeon faculty rank included Assistant Professor (n = 5), Associate Professor (n = 4), and Professor (n = 5). Median surgeon experience during the study period with laparoscopic assessment was 13 cases (range 1-28) and TRS was 22.5 cases (range 2-48). The kappa inter-rater agreement was -0.017 (95% CI 0.023 to -0.005) indicating low inter-rater agreement between radiology review and actual laparoscopic score. The ICC in this model was 0.06 (0.02-0.21) indicating that surgeons do not score the same across all the images. When using a clinical cutoff of PIV of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI: 0.49-0.73). Number of laparoscopic cases, TRS cases, or faculty rank was not significantly associated with agreement. Conclusions: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. 44% of patients in our study may have been inadequately triaged by radiology review alone, which may have led to suboptimal TRS. Our study highlights the utility of laparoscopic scoring assessment to determine resectability over radiology assessment alone in ovarian cancer.
Development of radiotherapeutic rhenium-188 liposomes in alginate microspheres (Rhe-LAMs) for treatment of liver tumors and technetium-99m liposomes in alginate microspheres (Tech-LAMs) for image-guided treatment planning.
Authors: Ryan D. Bitar, Jorge Lopera, Ande Bao, Jaclyn Merlo, Francisco Cigarroa, William Phillips
Journal: Journal of Clinical Oncology (2019)

e15599 Background: Radio-embolic agents such as beta-emitting yttrium-90 spheres have been widely adopted as a modality for liver cancer therapy; however, their production can be timely and costly, shunting to the lungs may occur, and post-procedural visualization is limited. Alginate, a polysaccharide which can easily be formed into microspheres, has already been investigated for drug delivery applications; however, we propose utilizing alginate to manufacture radioembolic microspheres for intra-arterial delivery to liver tumors: Rhenium-188/186-labeled liposomes in alginate microspheres (Rhe-LAMS) as a radioembolic agent for the treatment of liver tumors and technetium-99m labeled liposomes in alginate microspheres (Tech-LAMs) as an agent for nuclear image-guided pre-treatment planning for liver cancer patients. Methods: Liposomes were manufactured and labeled with either Re-188/186 or Tc-99m. The liposomes were then mixed with alginate solution and then cross-linked with CaCl 2 to form microspheres. Microsphere diameter was evaluated via light microscopy, and retention of radioactivity was measured over time via dosimeter. Microspheres containing free Re-186/Tc-99m (i.e. no liposomes) were also constructed for control comparison. To test in vivo stability, Tech-LAMs were intra-arterially injected into the liver of rabbits for nuclear imaging. Results: 2 ml batches of Rhe-LAMS/Tech-LAMS of 20-80 microns could be manufactured in 3 hours. Radiolabeling efficiency of the liposomes reached 85% and retention of radioactivity in microspheres reached 75%. After overnight incubation, 90% activity was retained. Control microspheres showed a retention of &lt; 5%. In vivo imaging revealed absent activity in the lungs and high embolic activity in the liver. Conclusions: Our novel method demonstrated success regarding radioactivity retention and embolization capabilities. We envision this method to be a quickly-producible, cost-efficient, and effective means for radioembolization of liver tumors that could be adopted by any radiopharmacy.
Case 8-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Bruce Furie, Gail Moskowitz
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 65-year-old woman was admitted to the hospital because of thrombocytopenia and uterine carcinoma with vaginal bleeding.There was a five-year history of intermittent vaginal bleeding that was ascribed to uterine leiomyomas; a hysterectomy was advised, but the patient declined. Three months before admission another episode of vaginal bleeding occurred, and a physician prescribed iron. One month before entry vaginal bleeding resumed, with a watery discharge, and evaluation elsewhere showed the presence of endometrial carcinoma. One week before admission, because of increasing vaginal bleeding, the patient was admitted to another hospital, where radiation treatment to the pelvis . . .
Results of randomized phase II trial of neoadjuvant carboplatin plus docetaxel or carboplatin plus paclitaxel followed by AC in stage I-III triple-negative breast cancer (NCT02413320).
Authors: Priyanka Sharma, Bruce F. Kimler, Anne O'Dea, Lauren Elizabeth Nye, Yen Y. Wang, Rachel Yoder, Lindsey Hastings Prochaska, Jamie L. Wagner, Amanda Leigh Amin, Kelsey Larson, Christa Balanoff, Manana Elia, Gregory James Crane, Sheshadri Madhusudhana, Marc Steven Hoffmann, Maureen Sheehan, Robert R. Rodriguez, Roy A. Jensen, Andrew K. Godwin, Qamar J. Khan
Journal: Journal of Clinical Oncology (2019)

516 Background: Addition of neoadjuvant carboplatin (Cb) to paclitaxel (T) followed by doxorubicin + cyclophosphamide (AC) improves pathologic complete response (pCR) rate compared to T/AC in TNBC. An anthracycline-free regimen of Cb plus docetaxel (D) also yields high pCR rates in TNBC, and patients achieving pCR with this regimen demonstrate excellent 3-year outcomes without adjuvant anthracycline. This study was designed to compare the efficacy of neoadjuvant regimens CbT→AC and CbD in TNBC. Methods: In this multicenter study, eligible patients with stage I–III TNBC were randomized (1:1) to either paclitaxel 80 mg/m2 every week X 12 + carboplatin (AUC 6) every 3 weeks X 4, followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 every 2 weeks X 4 (CbT→AC, Arm A), or to carboplatin (AUC 6) + docetaxel (75 mg/m2) every 21 days X 6 cycles (CbD, Arm B). The primary endpoint was pCR (no evidence of invasive tumor in the breast and axilla). The two regimens were compared for differences in pCR, residual cancer burden (RCB), treatment delivery, and toxicity. Results: Between 2015 and 2018, 100 patients were randomized; 48 to Arm A and 52 to Arm B. Median age was 52 years, median tumor size was 2.7 cm, 30% were lymph node-positive and 17% carried a BRCA1/2 mutation. Baseline demographic and tumor characteristics were balanced between two arms. pCR was 55% (95%CI: 41%-59%) in Arm A and 52% (95%CI: 39%-65%) in Arm B, p = 0.84. RCB 0+1 rate was 67% in both arms. Grade 3/4 adverse events were more common in Arm A compared to Arm B (73% vs 21%, p &lt; 0.0001), with most notable differences in rates of G3/4 neutropenia (Arm A = 60%, Arm B = 8%, p = 0.0001), febrile neutropenia (Arm A = 18%, Arm B = 0%, p = 0.0001), and G3/4 anemia (Arm A = 46%, Arm B = 4%, p = 0.0001). 81% of Arm A patients completed all 4 doses of AC and 4 doses of Cb, and 71% completed &gt; 9 doses of T. 90% of Arm B patients completed all 6 doses of CbD (p = 0.034). Conclusions: The non-anthracycline platinum regimen of CbD yields pCR and RCB 0+1 rates similar to 4-drug regimen of CbTàAC, but with a more favorable toxicity profile and higher treatment completion rate. The CbD regimen should be further explored as a way to de-escalate therapy in TNBC. Clinical trial information: NCT02413320.
Effects of a community-based pulmonary rehabilitation programme during acute exacerbations of chronic obstructive pulmonary disease – A quasi-experimental pilot study
Authors: A. Machado, A. Oliveira, C. Valente, C. Burtin, A. Marques
Journal: Pulmonology (2019)

Pulmonary rehabilitation (PR) is a cornerstone intervention for the management of patients with stable chronic obstructive pulmonary disease (COPD). However, its role during acute exacerbations (AECOPD) is controversial since most studies have been conducted in hospitalised patients, when more than 80% of AECOPD are managed on an outpatient basis. This quasi-experimental pilot study assessed the effects of a community-based PR programme during mild-to-moderate AECOPD.Outpatients were recruited from hospitals and allocated to experimental (EG) or control (CG) groups. EG received standard medication plus 3-weeks of PR. The CG received standard medication. Dyspnoea (mMRC), quadriceps muscle strength (QMS), functionality (5-repetition sit-to-stand test) and impact of the disease (COPD assessment test (CAT)) were assessed within 48h of the AECOPD onset and after PR. Symptoms of dyspnoea and fatigue (mBorg), heart and respiratory (RR) rates and peripheral oxygen saturation (SpO2) were assessed at rest and monitored in all PR sessions. Need for hospitalisation was monitored during the 3-weeks.Twelve patients (69±7 years, FEV1 52±27 pp) in the EG and eleven in the CG (66±9 years, FEV1 55±22 pp) were enrolled. The EG presented significant improvements on QMS (Pre 21.0 vs. Post 25.0, p=0.012), CAT (Pre 23.0 vs. Post 14.5, p=0.008), symptoms of dyspnoea at rest (Pre 3.0 vs. Post 1.0, p=0.008), SpO2 (Pre 94.0 vs. Post 96.0, p=0.031) and RR (Pre 24.0 vs. Post 20.5, p=0.004). No significant improvements were found in the CG.Adding PR to the management of mild-to-moderate AECOPD seems to result in improvements on parameters usually associated with an increased risk of re-exacerbation and poor prognosis. Randomised studies with larger samples are needed to confirm these results.
Phase Ib clinical investigation of intraperitoneal ipilimumab and nivolumab in patients with peritoneal carcinomatosis due to gynecologic malignancy.
Authors: Emily Hinchcliff, Weiyi Peng, Virginia Bayer, Cara L. Haymaker, Steven Y Huang, Rahul Sheth, Shannon Neville Westin, Karen H. Lu, Patrick Hwu, Amir A. Jazaeri
Journal: Journal of Clinical Oncology (2019)

TPS5606 Background: The peritoneal cavity is a frequent site of metastasis and recurrence for gynecologic malignancy, including approximately 80% of epithelial ovarian cancer (EOC) that presents with peritoneal involvement. These observations have led to the use of intraperitoneal (IP) route of administration for traditional cytotoxic chemotherapy. IP immunotherapy is a recognized but under explored area of clinical investigation with many potential advantages. Indeed, IP administered antibodies in both animals and human subjects are associated with absent or much lower peripheral blood concentrations. In addition to higher local and lower systemic exposure, other theoretical advantages include preferential binding to intraperitoneal and intratumoral immune cells, and absorption through the draining lymphatics of the peritoneal cavity. These pelvic and peri-aortic lymph nodes represent the most relevant lymphoid organs and as such may be the ideal site for T cell activation and trafficking back to the peritoneal tumor. Methods: The trial (NCT03508570) is a single-institution phase Ib trial to determine the recommended phase II dosing (RP2D) of IP administration of nivolumab in combination with ipilimumab. For the purpose of dose finding, the assessment period for dose limiting toxicity (DLT) is 12 weeks. The trial starts with a safety lead-in to confirm the safety of IP nivolumab before combining it with ipilimumab. A maximum sample size of 12 will be used to find the RP2D for nivolumab, up to 24 patients for the combination, and a planned expansion will be carried out such that at least 12 EOC patients are treated at RP2D of the intraperitoneal combination strategy. The secondary objectives are to describe the pharmacokinetics and toxicities, and to estimate the clinical benefit rate for the expansion cohort. Translational objectives include description of immunologic and biologic changes in serial blood and IP fluid collections as well as pre and on-treatment biopsies. Eligibility criteria include recurrent or progressive biopsy-confirmed platinum resistant EOC or other gynecologic cancer with measurable peritoneal disease, and no exposure to prior treatment with checkpoint inhibition. Enrollment began in January of 2019 with 3 subjects enrolled to date. Accrual update will be provided at the annual meeting. Clinical trial information: NCT03508570.
Active search for toxicity reduces delay on chemotherapy.
Authors: Juliana Souza, Daniele Neves
Journal: Journal of Clinical Oncology (2019)

6548 Background: Interdisciplinary teamwork involves health care professionals working as a team with the purpose of discussing individual cases and recommending care plans. In october 2015, the breast cancer interdisciplinary team (BCIT) was implemented in our outpatient oncology clinic. This team includes oncology physician, pharmaceutist, psychologist, nutritionist and oncology nurse. Since 2018, the oncology nurse does active search for toxicity (AST) in order to solve early symptoms. Methods: We evaluated outcomes of breast cancer patients who finished neoadjuvant/adjuvant chemotherapy and received BCIT care at our oncology clinic from october 2015 to November 2018. Results: Of 200 pts who had finish treatment, 139 pts (69.5%) received adjuvant chemotherapy and 61 pts (30.5%) neoadjuvant schedule. Median age was 52,64 years (range:30.6-82.3y). At diagnosis, 50 pts (25%) were stage I, 101 pts (50.5%) were stage II, and 49 pts (24.5%) were stage III. When we compared before and after AST, there were no significant difference between mean age (54.13y vs 54.06y, p:0.97), colony stimulating factor use (p:0.10), cold-cap use (p:0.81), and timing of chemotherapy (p:0.13). There were 7 hospitalizations during chemotherapy, with no significant difference with AST (5pt vs 2pt, p: 0.82). However, patients in AST had significantly lower mean delay to complete chemotherapy (9.4 days vs 4.2 days p:0.003). After median follow up 17 months, there were 9 progression disease and 4 deaths. 1-year and 3-year overall survival rate was 99,2% and 95,1%, respectively. Conclusions: AST increased adherence to chemotherapy, with lower delay on chemotherapy treatment. There were no significant difference with colony stimulating factor use, cold-cap use, timing of chemotherapy, and hospitalization.
Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study
Authors: Anaïs Rico-Campà, Miguel A Martínez-González, Ismael Alvarez-Alvarez, Raquel de Deus Mendonça, Carmen de la Fuente-Arrillaga, Clara Gómez-Donoso, Maira Bes-Rastrollo
Journal: BMJ (2019)

Abstract Objective To evaluate the association between consumption of ultra-processed foods and all cause mortality. Design Prospective cohort study. Setting Seguimiento Universidad de Navarra (SUN) cohort of university graduates, Spain 1999-2018. Participants 19 899 participants (12 113 women and 7786 men) aged 20-91 years followed-up every two years between December 1999 and February 2014 for food and drink consumption, classified according to the degree of processing by the NOVA classification, and evaluated through a validated 136 item food frequency questionnaire. Main outcome measure Association between consumption of energy adjusted ultra-processed foods categorised into quarters (low, low-medium, medium-high, and high consumption) and all cause mortality, using multivariable Cox proportional hazard models. Results 335 deaths occurred during 200 432 persons years of follow-up. Participants in the highest quarter (high consumption) of ultra-processed foods consumption had a higher hazard for all cause mortality compared with those in the lowest quarter (multivariable adjusted hazard ratio 1.62, 95% confidence interval 1.13 to 2.33) with a significant dose-response relation (P for linear trend=0.005). For each additional serving of ultra-processed foods, all cause mortality relatively increased by 18% (adjusted hazard ratio 1.18, 95% confidence interval 1.05 to 1.33). Conclusions A higher consumption of ultra-processed foods (&gt;4 servings daily) was independently associated with a 62% relatively increased hazard for all cause mortality. For each additional serving of ultra-processed food, all cause mortality increased by 18%. Study registration ClinicalTrials.gov NCT02669602 .
Choledochoenterostomy in Chronic Relapsing Pancreatitis
Authors: Louis M. Rousselot, Rafael Sanchez-Ubeda, Stanley Giannelli
Journal: New England Journal of Medicine (1954)

THE management of pancreatitis in the chronic phase is a vexatious problem, particularly in the stage variously referred to as chronic relapsing pancreatitis, acute recurrent pancreatitis and subacute pancreatitis. The medical or nonoperative prevention of recurrences of acute pancreatitis has been difficult to evaluate, but seems ineffectual in most cases. The surgical approach, in general, is also unsatisfactory, as attested by the many varied procedures that have been advocated at different clinics. Chronic atrophic pancreatitis is an equally difficult problem for medical or surgical management, digestive and metabolic disturbances and pain being the symptoms most characteristic of this late stage . . .
Mutant KRAS and TP53 with high mutation allelic frequency in ctDNA as poor outcome predictors in metastatic pancreatic cancer.
Authors: Shasha Guan, Yan Shi, Quanli Han, Jie Li, Yao Lv, Huan Yan, Lu Han, Yang Chen, Niansong Qian, Zhikuan Wang, Huaiyin Shi, Guanghai Dai
Journal: Journal of Clinical Oncology (2019)

e15763 Background: This study was to investigate the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in metastatic pancreatic cancer (MPC). Methods: From 2015 to 2018 in our center, 40 MPC patients treated with nab-paclitaxel based first-line chemotherapy were prospectively collected both tumor tissue and blood samples, in which the genomic profiling of 425 genes was identified by next-generation sequencing. High mutation allelic frequency (MAF) was defined &gt; 30% and &gt; 5% in tumor tissue and blood, respectively. Kappa statistics were used to compare mutant (mt) genes in tissue and ctDNA. Progression-free and overall survival (PFS, OS) were assessed with Kaplan-Meier and Cox methods. Results: Among 40 MPC patients, tumor tissue and blood samples were available in 34 and 38 patients for somatic and germline alternation test, respectively. The most commonly mutant gene were KRAS (31/34 in tissue with a median MAF of 29.4%, 29/38 in ctDNA with a mMAF of 8.2%), and TP53 (28/34 in tissue with a mMAF of 31.1%, 25/38 in ctDNA with a mMAF of 7.4%). Moderate agreement was seen between ctDNA and tumor tissue (mt KRAS: κ = 0.54, P = 0.001; mt TP53: κ = 0.74, P &lt; 0.001). Mutation in CDNK2A and SMAD4 genes were detected in 8 and 6 patients in tissue and ctDNA, respectively. Germline alternation was found in 7 genes in 9 patients (9/40). High MAF of mt KRAS (r = 0.51, P = 0.005) or mt TP53 (r = 0.50, P = 0.005) in ctDNA was correlated with high CA199 levels (&gt; 5000 u/ml) at baseline. MT KRAS in tissue with high MAF was associated with poor OS (high 7.5m vs low 10.1m, P = 0.001) in univariate and multivariate analyses (HR 3.87, 95%CI 1.47 to 10.19). Univariate analyses showed mt KRAS and mt TP53 in ctDNA with high MAF were associated with poor PFS ( KRAS and TP53: high 3.4m and 3.0m vs low 6.1m and 5.7m, P = 0.001 and P = 0.004, respectively) and OS ( KRAS and TP53: high 5.3m and 5.3m vs low 12.6m and 10.1m, P &lt; 0.001, respectively). The presence of ctDNA in any above four mt driver gene with high MAF was associated with poor PFS (HR 3.79, 95%CI 1.71 to 8.42) and OS (HR 7.21, 95%CI 2.69 to 19.34) in multivariate COX model, when adjusted by age, sex, tumor differentiation, and baseline CA199 level. Conclusions: The presence of mt KRAS and mt TP53 with high MAF in ctDNA was associated with worse PFS and OS in MPC patients. Peripheral ctDNA testing demonstrated an alternative promising prognostic biomarker for MPC patients before treatment.
Afatinib in the treatment of advanced NSCLC with EGFR mutation: An observational real-world study.
Authors: Yun Li, Xiaohua Wang, Li Wang, Yingying Kou, Xianglei Ma, Ji Feng Feng, Mingzhe Xiao, Meiqi Shi, Yiqun Tang
Journal: Journal of Clinical Oncology (2019)

e20518 Background: Compared with the first generation of EGFR-TKI, Afatinib has a broader spectrum of activity and can better inhibit tumor growth. At present, the therapeutic effects of Afatinib varies on patients with different EGFR mutations and studies on the mechanism of acquired Afatinib resistance are limited. The aim of this study was to evaluate the efficacy and safety of Afatinib in the treatment of EGFR-mutation NSCLC who hadn’t received EGFR-TKI in the past. Methods: 88 patients with advanced NSCLC who had EGFR mutations were enrolled and given oral 40 mg Afatinib daily until disease progression or adverse events that could not be handled by dosage reduction. Efficacy and safety in different subgroups were analyzed. Results: Among 88 patients, the common mutation rate of EGFR was 79.5%, and the rare mutation rate was 20.5%. The objective remission rate (ORR) was 54.5%, and the disease control rate (DCR) was 92.0%. The median progression-free survival (PFS) was 14.2 months (95% CI 11.4-18.5), 27 patients (30.7%) continued Afatinib treatment after tumor progression, and the median time to progression of clinical symptoms (TTSP) was 16.3 months (95% CI 12.7-19.3). A total of 13 patients (14.8%) reduced Afatinib dosage of due to adverse events. Subgroup analysis showed that Afatinib had better effect on patients harboring common EGFR mutation but not exon 20 mutation, and was not affected by brain metastasis, dosage and lines of therapy. Among patients who progressed on Afatinib, 65.4% harbored T790M mutation. Most T790M patients received the third generation EGFR-TKI including AZD9291 and oxetinib treatment. The most common adverse reactions were diarrhea, rash, paronychia and stomatitis. Conclusions: Afatinib showed good efficacy and tolerance in advanced NSCLC patients with EGFR mutations. Continuation of Afatinib treatment after cancer progression could delay the progression of disease symptoms. The third generation EGFR-TKI could become a treatment option after Afatinib resistance. These findings reflected the real-world clinical practice of Afatinib.