tbuckley/cabot-search huggingface dataset:
Cause of death among patients with non-small cell lung cancer treated with postoperative radiation therapy (PORT).
Authors: Aashray Singareddy, Saiama Naheed Waqar, Siddhartha Devarakonda, Jeffrey P. Ward, Ramaswamy Govindan, Clifford Robinson, Daniel Morgensztern, Pamela Parker Samson
Journal: Journal of Clinical Oncology (2021)

e20555 Background: The indications for post-operative radiation therapy (PORT) in locally advanced non-small cell lung cancer (NSCLC) remain undefined and a major concern is the perceived risk of increased mortality from cardiopulmonary causes. The purpose of this study was to quantify the rate of cardiopulmonary death in patients with resected NSCLC receiving PORT using a large national database. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database for lung cancer, patients with Stage IIIA or Stage IIIB NSCLC according to the 6 th AJCC edition treated with surgery followed by PORT, who also received chemotherapy were identified. Cause of death was categorized as due to lung cancer, other cancer, cardiac, pulmonary, or other and reported as a percentage of total deaths at one and 2 years. Kaplan-Meier survival analysis was done to compare overall survival between Stage IIIA and IIIB patients. Results: From 2004 to 2015, 4387 patients with stage IIIA and IIIB meeting the eligibility criteria were identified. The median age at diagnosis was 65 years old, most patients were male (53%), Caucasian (83%), had adenocarcinoma (54.8%), stage IIIA disease (69%), and N2 disease (78%). The median overall survival for Stage IIIA and IIIB patients was 39 months and 27 months respectively (p &lt; 0.001). Among the 2586 patients that died during the study period, the most common COD was lung cancer (81.3%). Cardiac and pulmonary COD occurred in 86 patients (3.3% of deaths) and 84 patients (3.2% of deaths) respectively, whereas 158 patients (6.1%) died from other cancers and 154 (5.9%) from other causes. There were 77 deaths from cardiopulmonary cause at 2 years (1.7% of patients and 2.9% of deaths). Cardiopulmonary COD was more common in patients with stage IIIB compared to IIIA disease (4.9% vs 3.3% of deaths, p &lt; 0.001). Lung cancer was the most common COD both at 1 and 2 years (85%) whereas cardiopulmonary was the COD in 5.2% of patients at 1 year and 5.1% at 2 years. Conclusions: This analysis showed a low cardiopulmonary mortality from PORT in the first 2 years. The role for adjuvant radiotherapy remains undefined and treatment decisions for patients with resected stage III NSCLC should be guided by co-morbidities and the competing risk for death from lung cancer.
Traction-assisted endoscopic submucosal dissection with submucosal tunneling for Barrett’s esophagus nodularity
Authors: Rodrigo Duarte-Chavez, Marina Kim, Daniel Marino, Michel Kahaleh
Journal: Endoscopy (2021)

Barrett's esophagus (BE) is a premalignant condition with significant risk for esophageal adenocarcinoma. Endoscopic therapy is recommended after mucosal irregularities are found during surveillance [1]. Endoscopic mucosal resection (EMR) is sufficient to determine the depth of invasion. However, endoscopic submucosal dissection (ESD) facilitates en bloc resection and provides better assessment of the lateral margin of the lesion. ESD is technically more difficult than EMR but can be performed when bulky lesions are encountered or when submucosal invasion is suspected [1] [2].
Pazopanib in the advanced and rare subtypes of soft tissue sarcoma: Russian Sarcoma Group study.
Authors: Anastasia Alekseevna Tararykova, Beniamin Bokhyan, Andrey A. Konev, Polina A. Falkina, Zaur Yu. Kumekhov, Aslan K. Valiev
Journal: Journal of Clinical Oncology (2021)

e23528 Background: Sarcoma is a heterogeneous group of tumors that arise from connective tissue. The most frequent localizations of primary tumors are soft tissues and bones of the extremities, and the lungs is the most common localization of metastases. Pazopanib is an antineoplastic agent, multi-kinase inhibitor that retards angiogenesis in tumor tissues and has been shown to be effective in the treatment of patients with advanced sarcoma. Median progression-free survival was 4,6 months (95% CI 3,7–4,8) for pazopanib compared with 1,6 months (0,9–1,8) for placebo in the PALETTE clinical trial. This study designed to detect epidemiology data as well as the pazopanib efficiency for rare sarcoma subtypes. Methods: We collected data from 109 cases with 20 different sarcoma histotypes and 15 localizations, at N.N. Blokhin National Medical Research Center of Oncology from 2018 till 2020. Disease was histologically confirmed by a sarcoma pathologist. The average age of patients was 47.8 years and the women and men ratio was about 2:1. Patients received pazopanib 800 mg once daily and passed control examinations every 2 or 3 months (CT/MRI). Treatment response was assessed by RECIST criteria. Results: The most frequent localizations of primary tumors were the soft tissues of the extremities (39.6%), the uterus (16.9%) and the retroperitoneum (13.2%). The main histological subtypes were leiomyosarcoma (33.6%) and synovial sarcoma (14.9%). There were also included such types like a embryonal rhabdomyosarcoma, chondrosarcoma, Ewing tumors, EHE, alveolar soft part sarcoma, PEComa, clear cell sarcoma, adamantinoma, solitary fibrous tumor, epithelioid sarcoma and myxoid liposarcoma. The majority of patients (61%) received more than 2 of therapy. The average duration of therapy was 7.5 months. Best tumor response by RECIST was as follows: complete response 0 (0%), partial response 2 (2%), stable disease 81 (88,3%), progression disease 25 (27,3%) cases. Median progression-free survival was 8 months (95% CI 6,7-9,2) for pazopanib. Median overall survival was not reached. Overall pazopanib was well tolerated, except one case with SAE. Conclusions: In this study we observed pazopanib efficiency in a rare for pazopanib sarcoma subtypes such as myxoid liposarcoma (1 PR), PEComa, adamantinoma, embryonal rhabdomyosarcoma, malignant peripheral nerve sheath tumor and Ewing tumors. Also our study confirms pazopanib long-term disease control in alveolar soft part sarcoma, clear cell sarcoma, leiomyosarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma which explains median PFS 8 months.
Effect of competing mortality risks on predictive performance of the QRISK3 cardiovascular risk prediction tool in older people and those with comorbidity: external validation population cohort study
Authors: Shona Livingstone, Daniel R Morales, Peter T Donnan, Katherine Payne, Alexander J Thompson, Ji-Hee Youn, Bruce Guthrie
Journal: The Lancet Healthy Longevity (2021)

Primary prevention of cardiovascular disease (CVD) is guided by risk-prediction tools, but these rarely account for the risk of dying from other conditions (ie, competing mortality risk). In England and Wales, the recommended risk-prediction tool is QRISK2, and a new version (QRISK3) has been derived and internally validated. We aimed to externally validate QRISK3 and to assess the effects of competing mortality risk on its predictive performance.
Isolated same-basin lymph node recurrence after precision lymph node excision for clinically evident melanoma metastasis.
Authors: Kevin Lynch, Yinin Hu, Norma Farrow, Yun Song, Max Meneveau, Minyoung Kwak, Michael C. Lowe, Edmund Bartlett, Georgia Beasley, Giorgos Karakousis, Craig L. Slingluff
Journal: Journal of Clinical Oncology (2021)

9576 Background: While management of the nodal basin for melanoma has largely moved to observation for microscopic sentinel lymph node (SLN) metastasis, complete lymph node dissection (CLND) remains the current standard of care for melanoma patients with macroscopic, clinically detectable lymph node metastases (cLN). As CLND is associated with high surgical morbidity, we sought to study whether cLN may be safely managed by excision of only clinically abnormal nodes (precision lymph node dissection, PLND). Currently, a small subset of patients with cLN do not undergo CLND because of frailty or patient preference. We hypothesized that in these selected patients, PLND would provide acceptable regional control rates. Methods: Retrospective chart review was conducted at four academic tertiary care hospitals to identify melanoma patients who underwent PLND for cLN. cLN were defined as palpable or radiographically abnormal nodes. Recurrences were categorized as local/in-transit, same-basin lymph node, or distal lymph node/visceral. The primary outcome was isolated same-basin recurrence after PLND. Results: Twenty-one patients underwent PLND for cLN without synchronous distant metastases (characteristics of primary lesions summarized in Table). Reasons for forgoing CLND included patient preference (n=8), imaging indeterminate for distant metastases (n=2), comorbidities (n=4), loss to follow up (n=1), partial response to checkpoint blockade (n=1), or not reported (n=5). The inguinal node basin was the most common site (n=10), followed by the axillary (n=8) and cervical basins (n=3). A median of 2 nodes were resected at PLND, and 68% of resected nodes were positive for melanoma (median: 1, range: 1-3 nodes). Median follow-up was 23 months from PLND, and recurrence was observed in 28.6% of patients overall. Only 1 patient (4.8%) developed an isolated same-basin recurrence. The 3-year cumulative incidence of isolated same-basin recurrence was 5.3%, while risk of isolated local/in-transit recurrence or distant basin/visceral metastasis were 19.8% and 33.3%, respectively. Complications from PLND were reported in 1 patient (4.8%) and were limited to post-operative seroma and lymphedema. Conclusions: These pilot data suggest that PLND may offer acceptable regional disease control for cLN. Post-operative morbidity from PLND was also low, raising the possibility that PLND may provide adequate regional disease control without the morbidity associated with CLND. These data justify additional, prospective evaluation of PLND in selected patients.[Table: see text]
U.S. budget impactanalysis of body surface area (BSA)dosing for a rituximab biosimilar vsflat-fixed-dosing for subcutaneous rituximab in non-Hodgkin lymphoma (NHL)and chronic lymphocytic leukemia (CLL).
Authors: Stephen Thompson, Holly Trautman, Ali McBride, Azhar Choudhry, Elizabeth James
Journal: Journal of Clinical Oncology (2021)

e18822 Background: The first rituximab biosimilar approved in the US, rituximab-abbs, is a CD20-directed monoclonal antibody that is expected to significantly reduce drug acquisition costs. This economic analysis evaluated budgetary impact of BSA-based rituximab-abbs (IV-R-BIOSIM) vs flat-fixed rituximab/hyaluronidase human subcutaneous injection (SC-R) dosing in NHL (diffuse large B-cell lymphoma [DLBCL], follicular lymphoma [FL]) and CLL. The objective was to project incremental cost differences per patient between IV-R-BIOSIM and SC-R from a US healthcare insured (Medicare) population. Methods: An illustrative BIM estimated 1-year costs for IV-R-BIOSIM and SC-R. The model assumed equal efficacy and safety between products. Values for epidemiology, market share distribution, drug dosing, administration, and costs were derived from scientific literature, product labels, and publicly available cost resources. Costs for the first infused rituximab (IV-R) dose were excluded for appropriate comparison. IV-R-BIOSIM doses used BSAs of 1.6 m 2 , 1.8 m 2, infusion duration was 3 hours. Annual dose counts of IV-R-BIOSIM or SC-R were: 9 untreated FL with maintenance; 7 untreated FL (without maintenance), relapsed/refractory FL, or untreated DLBCL; 5 CLL. Drug acquisition and administration costs were from 2020 Average Sales Price pricing file and Centers for Medicare and Medicaid Services Physician Fee Schedule. Patient cost share was 2020 Medicare Part B 20% cost-share for office visits and drugs. A scenario analysis was also performed to estimate FL maintenance costs for 2-year dosing. Results: Estimated 1-year savings with IV-R-BIOSIM for 1.8 m 2 BSA dosing were $1,067–$6,893 with variability between indications (Table). For 1.6 m 2 BSA dosing, estimated 1-year savings with IV-R-BIOSIM were $3,819–$10,856. Estimated 2-year savings with IV-R-BIOSIM for FL maintenance dosing were $9,191 for 1.8 m 2 BSA dosing and $14,475 for 1.6 m 2 BSA dosing. Savings of up to $1,900 were seen for higher-than-average BSA dosing, regardless of regimen. Conclusions: These findings demonstrate the potential economic benefits of replacing a proportion of SC-R use with BSA-based IV-R-BIOSIM from a US payer perspective, especially when lower BSA dosing is used. Savings are driven by drug costs and may increase with IV-R-BIOSIM as patient BSA decreases due to static costs with SC-R doses. These data also suggest that drug wastage may occur with SC-R in lower BSA patients.[Table: see text]
Exercise and QUality diet After Leukemia (The EQUAL Study): An intervention trial in the Childhood Cancer Survivor Study (CCSS).
Authors: Emily S. Tonorezos, Jeanne M. Clark, Chaya S. Moskowitz, Jennifer S. Ford, Gregory T. Armstrong, Joanne F. Chou, Nidha Z. Mubdi, Aaron McDonald, Charles A. Sklar, Lakshmi Ramanathan, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2021)

10015 Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for obesity and cardiovascular (CV) disease. Exposure to cranial radiotherapy (CRT) increases risks. We tested whether a weight loss intervention that was successful in the general population could result in weight loss or improvements CV risk factors for ALL survivors. Methods: Obese and overweight 5-year ALL survivors diagnosed &lt; age 21 from CCSS were randomized to a 24-month remotely delivered diet/physical activity intervention or self-directed weight loss (control), stratified by CRT. The intervention emphasized a low calorie DASH diet and physical activity via an app, a website, and weekly coach calls. The primary endpoint was difference in weight loss after 24 months, using an intent-to-treat analysis. Secondary endpoints: differences in changes in blood pressure, cholesterol, and triglycerides. Analyses were performed using linear mixed effects; the study was designed to detect a difference of 2.75 kg. Results: Of 358 survivors (59% female, 91% White non-Hispanic, median age 37, IQR: 33-43), 181 were randomized to the intervention and 177 to control. Baseline mean (SD) weight was 98.6 kg (24.0) for intervention and 94.9 kg (20.3) for controls. 55 (30%) of intervention participants were adherent beyond one year. At 12 months, after controlling for CRT, sex, race/ethnicity, and age, the adjusted mean (SE) change in weight from baseline was -1.83kg (0.7) for intervention and -0.16kg (0.64) for control participants. At 24 months, the adjusted mean (SE) change in weight was -0.36kg (0.78) for intervention and +0.18kg (0.66) for control participants with the average difference of -0.54 kg (95%CI: -2.5,1.5, p=0.59) between the arms. A small proportion had at least 5% weight loss at 24 months (intervention 24%; control 17%). No significant differences in CV risk factors were observed. Conclusions: A 24-month phone and app/web-based diet and physical activity intervention that was successful for weight loss in the general population did not result in greater weight loss or improvement in CV risk factors among adult survivors of childhood ALL. Reduced adherence to the intervention beyond 12 months, or lack of ALL survivor-specific tailoring, may account for these findings. Clinical trial information: NCT02244411. [Table: see text]
Prediction of long-term prognosis over ten years in ER-positive HER2-negative early-stage breast cancer using <sup>18</sup>F-FDG PET/CT before treatment.
Authors: Hiroko Tsukada, Jitsuro Tsukada, Eiichiro Noguchi, Takahiro Okamoto
Journal: Journal of Clinical Oncology (2021)

e12542 Background: Although ER-positive, HER2-negative early-stage breast cancer is considered to have a relatively good prognosis, it is known to occur long-term recurrence for more than 10 years. 18 F-FDG PET/CT has been reported to be useful in predicting short-term recurrence of breast cancer (2-5 years), but its correlation with long-term prognosis over ten years in ER-positive HER2-negative breast cancer is not clear. In the present study, we examined whether tumor FDG accumulation of pre-treatment PET/CT can be a predictor of long-term overall survival (OS) in ER-positive, HER2-negative early-stage breast cancer patients. Methods: Of 639 primary breast cancer patients treated at our institution between January 2007 and May 2010, 332 patients with stage 2 or less and ER-positive HER2-negative tumors who were able to confirm whether or not they had recurred at ten years postoperatively were included in the study. The impact of patients' characteristics, tumor background, and tumor FDG accumulation of pretreatment PET/CT image on OS was investigated using Cox regression analysis. P &lt; 0.05 was considered to be a statistically significant difference. Results: There were 33 (9.9%) recurrences and 13 (3.9%) deaths during a median observation period of 121 months. Univariate analysis showed that tumor SUVmax / FDG accumulation in lymph nodes / stage / N category / diameter of invasion / nuclear grade were candidate predictors of OS. Multivariate analysis revealed that SUVmax (Hazzard ratio 1.36 [95% CI 1.13-1.63], P &lt; 0.001) was the only predictor of OS. Conclusions: In patients with ER-positive HER2-negative early-stage breast cancer, tumor SUVmax on pretreatment PET/CT was the only independent predictor of OS.
Medically unexplained symptoms: (Letter 2 of 2)
Authors: S. Kumar
Journal: Journal of the Royal Society of Medicine (2003)

The review by Dr Page and Professor Wessely (May 2003 JRSM1) is timely and excellent. As they point out, medically unexplained symptoms (MUS) are probably the most common reason for attendance at general medical out-patient clinics. Yet students are not exposed adequately to this condition during either undergraduate or postgraduate training. Current medical training is so oriented as to make students always look for abnormal findings on examination. Therefore, when a doctor encounters a patient with MUS, the absence of physical abnormalities generates frustration. This is compounded by lack of effective pharmacological or surgical therapy. Very little research has been done on MUS considering the amount of suffering and financial loses they cause.

Despite the temptation to refer to multiple specialists, the best option for primary physicians is to keep patients with MUS under their own care. The lack of enthusiasm and the feeling of frustration engendered by these patients can lead to poor assessment and underinvestigation as well as multiple unnecessary investigations. Somehow a middle path has to be found. The drugs used for treatment of MUS commonly have adverse events and the mainstays of treatment are counselling, reassurance and periodic follow-up. These matters deserve detailed coverage in the medical curriculum.
HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults
Authors: Nila J. Dharan, Paul Yeh, Mark Bloch, Miriam M. Yeung, David Baker, Jerick Guinto, Norman Roth, Sarah Ftouni, Katherine Ognenovska, Don Smith, Jennifer F. Hoy, Ian Woolley, Catherine Pell, David J. Templeton, Neil Fraser, Nectarios Rose, Jolie Hutchinson, Kathy Petoumenos, Sarah-Jane Dawson, Mark N. Polizzotto, Mark A. Dawson, Trina Vincent, Ricardo Rosario, Helen Lau, Denise Smith, Sally Price, Jessica O’Brien, Hooi Theng Lynn Tan, Bret Sinclair, Florence Bascombe
Journal: Nature Medicine (2021)
An investigation on acquired mutations after TKI treatment in Chinese lung cancer patients.
Authors: Yong Jiang, Yingmei Li, Jiandong Zha, Danni Liu, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2021)

e21162 Background: Targeted therapy has greatly extended the survival of certain molecular selected cancer patients. However, lots of them would eventually develop drug resistance and required alternative treatment. Research on the genomic changes before and after treatment allows us to understand the mechanism of drug resistance and to develop new treatment strategies. Methods: A total of 143 patients were enrolled and their specimens were sequenced with a panel of 680 cancer-related genes in this study. Briefly, tumor FFPE samples before treatment (T1) were collected and underwent deep sequencing (2000X), and blood samples after treatment (T2) were collected, cell-free DNA (cfDNA) was isolated and sequenced (20000X). Patients with positive EGFR mutations at T1 received TKIs afterwards. Results: A total of 160 mutations were identified in T1 and 206 mutations were found in T2 samples, while 90 of them were shared in both time points. EGFR mutations were found in 95 (66.4%) patients at T1 and 101 (70.6%) patients at T2. ERBB2 mutations were found in 9 (6.3%) patients at T1 and 19 (13.3%) patients at T2. Among them, one patient had ERBB2 amplification at T1, and new ERBB2 amplifications were found in 11 patients at T2. Conclusions: ERBB2 amplifications are associated with TKI treatment, and are likely to be involved with disease progression and TKI drug resistance.
Targeting regulator of G protein signaling 1 in tumor-specific T cells enhances their trafficking to breast cancer
Authors: Di Huang, Xueman Chen, Xin Zeng, Liyan Lao, Jiaqian Li, Yue Xing, Yiwen Lu, Qian Ouyang, Jianing Chen, Linbin Yang, Fengxi Su, Herui Yao, Qiang Liu, Shicheng Su, Erwei Song
Journal: Nature Immunology (2021)
New Kidney and Pancreas Allocation Policy: Moving to a Circle as the First Unit of Allocation
Authors: Ajay Israni, Andrew Wey, Bryn Thompson, Jon Miller, Vincent Casingal, Martha Pavlakis, Silke Niederhaus, Rachel Forbes, Amber Wilk, Warren McKinney, Raja Kandaswamy, Peter Stock, Jon Snyder
Journal: Journal of the American Society of Nephrology (2021)

On May 31, 2018, the US Department of Health and Human Services received a critical comment raising concerns that the existing deceased donor liver allocation policy may not have been in compliance with the Organ Procurement and Transplantation Network (OPTN) Final Rule on deceased donor organ
Does malnutrition affect survival in cirrhosis?
Authors: M Merli, O Riggio, L Dally
Journal: Hepatology (1996)

A total of 1,053 cirrhotic patients were included in a prospective study to determine whether malnutrition is a risk factor for mortality in cirrhotic patients. Child-Pugh classification as well as clinical and biochemical variables were used to assess the severity of cirrhosis. Nutritional status was evaluated both by anthropometric and clinical measurements. Patients were defined as malnourished when midarm muscle area (MAMA) and/or midarm fat area (MAFA) were below the 5th percentile of an age- and sex-matched population. During follow-up, 419 patients died. The estimated survival rate was 82.7% at 1 year, 65.1% at 3 years, and 50.7% at 5 years. The presence of muscle depletion and/or of a steep reduction in fat deposits was associated with a higher risk of mortality (midarm muscle area, < 5th percentile, relative risk = 1.79; midarm fat area, < 5th percentile, relative risk = 1.35). When patients were stratified according to the Child-Pugh classification, cumulative survival was lower in patients with a reduction in muscle mass in Child-Pugh classes A and B (log rank: P = .027; P = .022, respectively) but not in class C. Conversely, a significant reduction in adipose tissue deposits appeared to have no independent impact on survival in any Child-Pugh class. When examined using a multivariate Cox proportional hazard analysis, age, sex, bilirubin, cholinesterase, ascites, and esophageal varices were selected, whereas the parameters of nutritional status were not. This suggests that malnutrition, while strongly associated with the deterioration of liver function, cannot be considered an independent risk factor for mortality in a general population of cirrhotic patients.
IFN-γ誘導可能なタンパク質-10(CXCL10)の、Thy1.1の糸球体腎炎における有足細胞を保護する新規な潜在能力
Authors: Han Gd, Koike H, Nakatsue T, Suzuki K, Narumi S, Shimizu F, Kawachi H
Journal: Journal of the American Society of Nephrology (2002)