tbuckley/cabot-search huggingface dataset:
Dissection of the lateral lymph nodes with short axis of ≥ 5 mm affects the prognosis in rectal cancer patients: A central review of 738 lower rectal cancer magnetic resonance images.
Authors: Koya Hida, Daisuke Nishizaki, Atsuhiko Sumii, Yoshiharu Sakai, Tsuyoshi Konishi, Tomonori Akagi, Tomohiro Yamaguchi, Takashi Akiyoshi, Meiki Fukuda, Seiichiro Yamamoto, Mamoru Uemura, Hirotoshi Hasegawa, Ryosuke Okamura, Michio Yamamoto, Kenji Kawada, Satoshi Morita, Masahiko Watanabe
Journal: Journal of Clinical Oncology (2019)

3578 Background: The usefulness of lateral lymph node dissection (LLND) for lower rectal cancer has been discussed. Concerning relapse-free survival (RFS), in the JCOG0212 trial, the non-inferiority of avoiding LLND for rectal cancer without LLN enlargement of ≥10 mm was not shown; however, the superiority of LLND was also not demonstrated. Methods: To examine whether the difference in dissection effect could be demonstrated by the size of LLN, magnetic resonance imaging (MRI) for the central review of pre-registered patients with stages II/III lower rectal cancer below the peritoneal reflection was performed, and the prognosis of the patients were prospectively investigated as a cohort. The relationship between LLND and RFS was also evaluated. Results: MR images of 738 cases (mean distance from anal verge: 4.5 cm) were evaluated. Twenty patients with LLN enlargement of ≥10 mm were excluded from the analysis. Overall, of 718 patients, 310 did not undergo LLND (non-LLND group), whereas the other 408 underwent LLND (LLND group). The lymph node sizes of ≥5 mm were observed in 10.0% and 21.1% of patients in the non-LLND and LLND groups, respectively. Although there was some bias in the background characteristics of the two groups (non-LLND vs. LLND; median age 66 vs. 61 years; laparoscopic surgery 64.2% vs. 17.9%; preoperative treatment 39.4% vs. 27.9%; circumferential resection margin evaluated by MRI 37.3% vs. 49.9%; and postoperative complications 33.2% vs. 44.4%), almost no difference in the 5-year RFS was observed (63.4% vs. 67.5%).The LLND group had significantly more favorable with ≥5 mm LLN (non-LLND 51.6% vs. LLND 69.0% P = 0.023) than with &lt; 5 mm LLN (non-LLND 64.7%; LLND 67.0%). Conclusions: Oncological benefit of LLND was suggested in patients with enlarged lateral nodes on MRI using a large cohort of clinical stage II/III lower rectal cancer.
Primary Immunodeficiency, a Possible Cause of Neutrophilic Necrotizing Dermatosis
Authors: Meri Kaustio, Timo Hautala, Mikko R. J. Seppänen
Journal: JAMA Dermatology (2019)

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One-year (yr) recurrence-free survival (RFS) from a randomized, open label phase II study of neoadjuvant (neo) talimogene laherparepvec (T-VEC) plus surgery (surgx) versus surgx for resectable stage IIIB-IVM1a melanoma (MEL).
Authors: Reinhard Dummer, David E. Gyorki, John Robert Hyngstrom, Adam C. Berger, Robert Martin Conry, Lev V. Demidov, Anjali Sharma, Sheryl Treichel, Mark B. Faries, Merrick I. Ross
Journal: Journal of Clinical Oncology (2019)

9520 Background: We previously reported that neo T-VEC + surgx resulted in a pathologic CR rate of 21% and an OR rate of 14.7% in a randomized trial of neo T-VEC + surgx vs upfront surgx in pts with resectable stage IIIB/C/IVM1a MEL (Andtbacka et al, ASCO 2018; NCT02211131). Here, we present results from an interim 1-yr analysis of RFS. Methods: Patients (pts) with resectable stage IIIB/C/IVM1a MEL, ≥ 1 injectable cutaneous, subcutaneous, or nodal lesions ≥ 10 mm, and no systemic tx 3 mos prior were randomized 1:1 to 6 doses/12 wks of T-VEC followed by surgx during wks 13-18 (Arm 1) vs upfront surgx during wks 1-6 (Arm 2). T-VEC was given at standard dosing until surgx, no injectable tumors, or intolerance. This analysis conducted on the ITT set estimated a between-group difference in 1-yr RFS per protocol. An RFS event was defined as the first of local, regional or distant recurrence or death due to any cause after surgx. Pts without a R0 surgical outcome or withdrew prior to surgx were considered an event at randomization for RFS. In a sensitivity analysis, RFS was calculated from randomization to the date of the first post-surgx event regardless of surgical outcome. Results: 150 pts were randomized (76 Arm 1, 74 Arm 2). Median (range) follow-up time was 20.6 (0.1, 38.5) mos in Arm 1 and 20.0 (0.1, 35.3) mos in Arm 2. 75% in Arm 1 and 93% in Arm 2 had surgx as planned. R0, R1, and R2 rates, respectively, for Arm 1 were 42.1%, 31.6%, and 1.3% and for Arm 2 were 37.8%, 51.4%, and 4.1%. At 1 yr, 33.5% of pts in Arm 1 and 21.9% of pts in Arm 2 remained recurrence free (HR 0.73, P= 0.048). From the sensitivity analysis, 55.8% of pts in Arm 1 and 39.3 % in Arm 2 remain recurrence free at 1 yr (HR 0.63, P= 0.024). OS rates at 1 yr were 95.9% in Arm 1 and 85.8% in Arm 2 (HR 0.47, P= 0.076). Pts receiving subsequent adjuvant tx was 8 (11%) in Arm 1 and 20 (29%) in Arm 2- most common was immunotherapy 6 (8.2%) and 8 (11.6%), respectively. Conclusions: In the largest randomized neo trial to date in resectable stage IIIB-IVM1a MEL, the following outcomes were improved with neo T-VEC monotherapy vs surgx: R0 surgical resections, 1-yr RFS, and OS. Primary analysis of RFS at 2 yrs is expected. Clinical trial information: NCT02211131.
Population kinetics of progression free survival (PFS).
Authors: David J. Stewart, Dominick Bossé, Andrew George Robinson, Michael Ong, Stephanie Yasmin Brule, Michael Fung-Kee-Fung, John Frederick Hilton, Mark J. Clemons, Alberto Ocana
Journal: Journal of Clinical Oncology (2019)

e18251 Background: We assessed drug type impact on whether PFS curves could be fit by 2 phase decay models on nonlinear regression analysis (NLRA). Methods: We digitized 894 published PFS curves for incurable cancers. We used GraphPad Prism 7 for 1 phase and 2 phase decay NLRA, with constraints Y 0 = 100 and plateau = 0. We defined curves as fitting 2 phase models if each subpopulation was ≥1% of the entire population and if subpopulation half-lives differed by a factor of ≥2, or if log-linear plots demonstrated unequivocal 2 phase decay. Results: PFS curves for single agents showed either high (≥75%) or low ( &lt; 30%) probability of 2 phase decay, depending on drug type (p &lt; 0.0001, Table). 11/11 PD1/ipilimumab combinations had 2 phase decay vs 36/209 curves (17%) for all other combinations. Conclusions: Drugs have either high or low probability of PFS curve 2 phase decay. Clinical trial methods or some mechanisms of acquired resistance might contribute to 2 phase decay, but 2 phase decay also could indicate a dichotomous factor (eg gene mutation/deletion or complete pathway silencing) producing 2 distinct subpopulations with differing progression rates. Drugs with high 2 phase decay could be prime candidates for RNA &amp; whole genome sequencing, pathway expression studies etc to identify dichotomous predictive factors. Further assessment is needed to better understand why some drugs behave differently when given in combinations vs as single agents. [Table: see text]
Adjuvant chemotherapy in small node-negative triple-negative breast cancer (TNBC).
Authors: Tessa Gerjanne Steenbruggen, Mette S. Van Ramshorst, Erik van Werkhoven, Vincent O. Dezentjé, Sabine Siesling, Sabine C. Linn, Gabe S. Sonke
Journal: Journal of Clinical Oncology (2019)

536 Background: International guidelines differ in their recommendation for adjuvant chemotherapy in small node negative TNBC. We evaluated associations of chemotherapy with long-term outcome in a large population-based TNBC cohort. Methods: All patients diagnosed with pT1N0M0 TNBC between 2005 and 2015 were identified from the Netherlands Cancer Registry. Patient, tumor and therapy characteristics were recorded. Date and cause of death were obtained from Statistics Netherlands. We used multivariable cox regression models to evaluate associations of chemotherapy with overall survival (OS) and breast-cancer specific survival (BCSS), adjusted for baseline characteristics. Subgroup analyses were performed by tumor size and grade. Results: We identified 4393 patients: 284 with T1a, 924 with T1b, and 3185 with T1c tumors. Chemotherapy was administered in 53% of patients: 6% with T1a, 17% with T1b and 67% with T1c. Chemotherapy use increased over time and varied by geographic region. Patients receiving chemotherapy were younger, had larger tumors, higher tumor grade, and more often isolated tumor cells (itc) in the lymph nodes. At a median follow-up of 7 years (IQR 5-10 years), 611 patients had died, of whom 287 due to breast cancer. Chemotherapy was associated with improved OS in the whole group (adjusted hazard ratio [aHR] 0.55; 95% CI 0.44–0.69), in the pT1c subgroup (aHR 0.53, 95% CI 0.41-0.67), and in grade 3 tumors (aHR 0.50, 95% CI 0.39-0.65). Associations were not significant for pT1ab or grade 1-2 tumors (table). Findings for BCSS were in line with OS results (table). To illustrate the absolute difference we estimated 10-year OS and BCSS for a 60-year old woman with a pT1cN0(itc+) grade 3 TNBC. The predicted 10-year OS was 67% with chemotherapy and 49% without; predictions for 10-year BCSS were 80% and 66%, respectively. Conclusions: Adjuvant chemotherapy is associated with higher OS and BCSS in small node negative TNBC. Benefit is most evident in grade 3 tumors and tumors &gt; 1cm and not evident in tumors ≤1cm and grade 1-2.[Table: see text]
Disparities in treatment patterns and overall survival (OS) in hormone receptor-positive HER2+ metastatic breast cancer (MBC): A National Cancer Database Analysis.
Authors: Abby Statler, Annie Gupta, Cassann N. Blake, Wei (Auston) Wei, Brian P Hobbs, Zeina A. Nahleh
Journal: Journal of Clinical Oncology (2019)

1032 Background: Determinants of variation in therapy utilization and OS are unclear for patients diagnosed with hormone receptor+, human epidermal growth factor 2 positive (HER2+) MBC. This study aimed to identify if there are disparities in first-line treatment patterns and outcomes for this subpopulation of MBC patients. Methods: We analyzed MBC patients included in the National Cancer Database diagnosed with estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+) and HER2+ disease (i.e. triple positive) treated with endocrine therapy or chemotherapy between 2010 and 2015. Analyses describe the distribution of treatments administered in the first-line setting. Kaplan-Meier method was used to estimate distributions of OS, which were compared among patient cohorts using the log-rank test. Results: Of the 6215 patients diagnosed with triple positive MBC, the majority were 50-70 years old (n=3414 [55%]), female (n= 6122 [98%]), and white (n=4478 [72%]). Four distinct treatment patters were identified; hormonal therapy was the most common (n= 2289 [37%]), followed by hormonal therapy + anit-HER2 (n=1471 [24%]), chemotherapy (1280 [20%]), and chemotherapy + anit-HER2 (n=1175 (19%)). Significant differences in demographic, socioeconomic, and disease characteristics were identified across groups. Disparities in OS were also observed; the unadjusted 5-year OS was substantially lower among older patients, African Americans (AA), those with government insurance, and lower income (Table). Conclusions: This is the first study to report disparities in treatment patterns and OS among real-world triple positive MBC patients. Further investigation is required to determine if there are independent causal associations between poor prognosis and the identified demographic and socioeconomic characteristics. [Table: see text]
The impact of NCI-sponsored network group clinical trials on guideline care and new drug indications.
Authors: Joseph M. Unger, Van T. Nghiem, Dawn L. Hershman, Riha Vaidya, Michael Leo LeBlanc, Charles David Blanke
Journal: Journal of Clinical Oncology (2019)

6604 Background: National Cancer Institute Clinical Trial Network (NCTN) groups serve a vital role in identifying new antineoplastic regimens. However, the clinical impact of their trials has not been systematically examined. We analyzed the influence of network group cancer clinical trials on clinical guidelines and new drug approvals. Methods: We evaluated Phase III cancer clinical trials which the SWOG Cancer Research Network coordinated or participated in (1980-2017). Included trials were completed and its results published. A documented practice influential (DPI) trial was one with verified influence on National Comprehensive Cancer Network (NCCN) clinical guidelines (available starting in 1996) or on U.S. Food and Drug Administration (FDA)-approved package inserts. We estimated the rate of DPI trials overall and over time. The total federal investment supporting the set of trials was also determined based on public data. Results: In total, 182 trials comprising 148,028 patients were studied. We identified 79 DPI studies (43.4%); 73 influenced NCCN guidelines, 12 influenced new drug approvals, and 6 influenced both. The rate of DPI trials was 72.3% (47/65) among formally positive trials (i.e., achieved their protocol specified endpoint) and 27.4% (32/117) among negative trials. Thus 40.5% (32/79) of DPI trials were based on negative studies, half of which (16/32 = 50.0%) reaffirmed standard of care over experimental therapy. There were no differences between DPI and non-DPI trials in key study design characteristics. Total federal investment for the programs conducting the trials was $1.36 billion (USD2017), a rate of $7.5 million per trial, or $17.2 million per DPI trial. Conclusions: Nearly half of all phase III trials by one of the NCTN’s largest groups had documented practice influence on clinical care guidelines or new drug approvals. Even many negative trials impacted guideline recommendations. Compared to the costs of a new drug approval in pharmaceutical companies – typically estimated at &gt; $1 billion – the amount invested by federal funders to provide this valuable evidence was modest. These findings highlight the major role of the NCTN’s clinical trial program in advancing oncology practice.
The healthiron study: A longitudinal study of environmental modifiers of hereditary hemochromatosis
Authors: Katrina J. Allen, Lyle C. Gurrin, Nick J. Osborne, Clare C. Constantine, Martin B. Delatycki, Amy E. Nisselle, John K. Olynyk, Amanda J. Nicoll, Dallasi R. English, Ashley S. Fletcher, John L. Hopper, Laurie W. Powell, Dorota M. Gertig
Journal: Hepatology (2006)
Cardiovascular mortality in renal cell carcinoma: A population-based study.
Authors: Michail Alevizakos, Apostolos Gaitanidis, Leonard Joseph Appleman
Journal: Journal of Clinical Oncology (2019)

e16085 Background: Patients with renal cell carcinoma (RCC) often harbor risk factors for cardiovascular disease and may receive anti-VEGF agents, which are associated with cardiovascular toxicity. However, the risk for cardiovascular mortality in this patient population is currently unknown. Methods: Utilizing the SEER database, we identified patients with RCC diagnosed between 2007 (approval of sunitinib) and 2015 and selected patients aged ≥ 45 years. We calculated standardized mortality ratios (SMRs) for cardiovascular mortality (ICD-10 codes I00-I99) by comparing the number of observed deaths in the database to the number of expected deaths in age-matched groups of the US general population drawn from the CDC WONDER database. Multivariable Cox regression was used to identify risk factors for cardiovascular mortality in patients with RCC. Results: We identified 36,576 patients with RCC, of which 33,748 (92.3%) were ≥ 45 years old and among these, 1650 (4.9%) died of cardiovascular diseases. The SMR for cardiovascular mortality was 2.85 (95% CI 2.72-2.99) for all patients, 2.78 (95% CI 2.62-2.95) for males and 2.86 (95% CI 2.64-3.10) for females. Among the various age groups, the SMR was 4.75 (95% CI 3.82-5.84) for patients aged 45-54 years, 3.35 (95% CI 2.93-3.83) for patients aged 55-64 years, 2.75 (95% CI 2.49-3.04) for patients aged 65-74 years, 2.25 (95% CI 2.07-2.45) for patients aged 75-84 years, and 1.47 (95% CI 1.33-1.61) for patients aged &gt; 85 years. In multivariate analysis, advancing age (HR 1.06, 95% CI 1.06-1.07), male sex (HR 1.18, 95% CI 1.05-1.33), black race (HR 1.48, 95% CI 1.27-1.73), stage IV disease (HR 1.21, 95% CI 1.01-1.45), and performance of surgery directed to the primary tumor (HR 0.33, 95% CI 0.29-0.38) were independently associated with cardiovascular mortality. Conclusions: Patients with RCC possess an almost 3-fold greater risk for cardiovascular mortality than the general population and this risk is even more pronounced in middle-aged patients. Aggressive management of modifiable cardiovascular risk factors in this patient population is thus warranted.
Preoperative conventional axillary ultrasound (AUS) and sonoelastography (SE) for predicting axillary lymph node metastasis in breast cancer patients.
Authors: Alexander Petrovsky, Nafset Khakurinova, Vladimir Sholokhov, Ramiz Valiev, Sergey Berdnikov, Igor Samoylenko, Victoria Amosova, Mikhail Nechushkin
Journal: Journal of Clinical Oncology (2019)

e12074 Background: Patients with operable breast cancer (BC) and clinically negative lymph nodes (CNLN) usually undergo sentinel lymph node biopsy (SNLB) or axillary lymph nodes dissection (ALND). AUS followed by fine-needle aspiration (FNA) or core-needle biopsy (CNB) could decrease number of unnecessary SNLBs and allow to assign patient to ALND directly. On the other hand, new AUS techniques such as SWE could enhance AUS specificity and allow to avoid SNLB in some patients. Aim: To assess sensitivity, specificity and negative predictive value of the AUS+SWE followed by FNA or CNB in patients with operable BC. Methods: Since Sep 2012 to Jan 2018 150 pts with operable BC and were enrolled. We include 30 pts in training cohort with clinically positive lymph nodes to verify AUS+SWE sensitivity and specificity. In validation cohort only those pts who were candidates for SNLB and who presented with tumor staging up to T3, and clinically negative axillae were included (n=120). All patients underwent preoperative AUS in B-mode, SWE, followed by FNA or CNB in case of suspicious nodes were detected. All pts underwent axilla surgery (SNLB = 46, ALND =74) and final pathology outcomes were available for all pts. Results: In training cohort of 30 patients with clinically positive lymph nodes the overall AUS+SWE sensitivity was set at 89.2%. The positive predictive value was calculated to be 96.1%. In the assessment of invasive breast tumors stages T1- T3 with clinically negative lymph nodes the sensitivity was 74.2%, specificity 95.5% positive predictive value was 85.2% and negative predictive value 91.4% If FNA or CNB follow the AUS+SWE in patients with CNLN the sensitivity was 86.7%, specificity 85.7% positive predictive value was 92.8% and negative predictive value was 75% (FNA or CNB was performed in 40 patients of 120 in validation set). Area under the ROC-curve was calculated as 0.860 [95% CI 0.766 to 0.954] for the US+SWE and 0.705 [95% CI 0.581 to 0.828] for the US+SWE followed by FNA or CNB. Conclusions: Axillary US+SWE should be included in the preoperative staging of all patients with invasive breast cancer. The addition US+SWE (not obviously followed by FNA or CNB) could lead to avoiding of unnecessary SNLB or ALND in patients with clinically and pathologically negative lymph nodes with negative predictive value of 91.4%. On the other hand in patients with US+SWE positive lymph nodes SNLB could also be skipped and the time interval to definitive therapy became shorter. Clinical trial information: BCA_US_SWE_001.
Results from neoadjuvant chemotherapy followed by surgery compared to chemoradiation for stage Ib2-IIb cervical cancer, EORTC 55994.
Authors: Gemma Kenter, Stefano Greggi, Ignace Vergote, Dionyssios Katsaros, Juliusz Kobierski, Leon Massuger, H. C. van Doorn, Fabio Landoni, Jacobus Van Der Velden, Nicholas Simon Reed, Corneel Coens, Iske van Luijk, P. B. Ottevanger, Antonio Casado
Journal: Journal of Clinical Oncology (2019)

5503 Background: Conflicting evidence on the value of neoadjuvant chemotherapy followed by surgery compared to concomitant chemoradiation in Stage IB2-IIB cervical carcinoma led to this multinational multicenter trial. As the trial is approaching completion of its follow-up, preliminary results are presented. Methods: Between May 2002 and June 2014 a total of 620 patients with FIGO stage Ib2-IIb were randomized between neoadjuvant chemotherapy followed by surgery (NACTS, arm 1, N=311) with standard concomitant chemoradiotherapy (CCRT, arm 2, N=309) . In arm 1, radical hysterectomy was required within 6 weeks after completion of cisplatin-based chemotherapy with a cumulative minimum of 225mg/m2, in arm 2, radiation consisted of 45-50 Gy plus boost concurrent with weekly cisplatin chemotherapy (40 mg/m2 per week). Primary endpoint was 5-yrs overall survival (OS). Results: Median follow-up time was 8.2 years ( 95% CI = 7.8 yrs – 8.6 yrs)) and similar between both arms. A total of 191 deaths (31%) occurred. Age, stage and histological cell type were balanced in both arms. Protocol treatment was completed in 459 (74%) patients (71% for NACTS; 82% for CCRT). In arm 1 238 (76%) patients underwent surgery. Main reasons for not having surgery as per protocol, were toxicity (25/74, 34%), progressive disease (18/74, 24%) and insufficient response to NACT (12/74, 16%). Additional radiotherapy was given to 113 patients (36.3%) in arm 1; additional surgery performed in 9 patients (2.9%) in arm 2. Short term severe adverse events (≥G3) occurred more frequently in arm 1 than in arm 2 (35% vs 21%, p &lt; 0.001). The 5 year OS was 72% in arm 1 and 76% in arm 2 (not statistically significant, difference = 4.0% (95%CI: -4% - 12%); HR 0.87, 95%CI: 0.65-0.15, p=0.332). Conclusions: These preliminary results revealed no difference in 5-year OS between NACTS and CCRT, indicating that quality of life and long term toxicity are important to decide optimal treatment. The final results will be available by April 2019, including long-term toxicity and treatment effect across prognostic factors. Clinical trial information: NCT00039338.
Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging
Authors: Hsin-Jung Yang, Ilkay Oksuz, Damini Dey, Jane Sykes, Michael Klein, John Butler, Michael S. Kovacs, Olivia Sobczyk, Ivan Cokic, Piotr J. Slomka, Xiaoming Bi, Debiao Li, Mourad Tighiouart, Sotirios A. Tsaftaris, Frank S. Prato, Joseph A. Fisher, Rohan Dharmakumar
Journal: Science Translational Medicine (2019)

Cardiac magnetic resonance imaging with repeat hypercapnia accurately detects myocardial oxygenation changes in a dog model of ischemic heart disease.