tbuckley/cabot-search huggingface dataset:
Clinical impact of postgastrectomy sarcopenia on the prognosis in patients with gastric cancer.
Authors: Beom Jin Kim, Eun Sun Lee, Joong-Min Park, In Gyu Hwang
Journal: Journal of Clinical Oncology (2020)

311 Background: There is a lack of research on newly developed sarcopenia postoperatively. The purpose of this study was to investigate the risk factors and the clinical impact of postgastrectomy sarcopenia on the prognosis in patients undergoing radical gastrectomy for gastric cancer (GC). Methods: We retrospectively reviewed clinicopathological data from 430 consecutive GC patients who underwent surgical resection at Chung-Ang University Hospital between January 2011 and December 2015. Their skeletal muscle mass and abdominal fat volume were measured by abdominal CT imaging. Results: A total of 425 patients were analyzed in the study. The mean age was 62 years old and male were 301 (70.8%). Of these, 42 patients (9.9%) were diagnosed as pre-operative sarcopenia. Compared with non-sarcopenic group, pre-operative sarcopenia groups showed more female, higher BMI, less alcoholic, and less smoking. However, there was no significant difference in 5 - year overall survival and disease free survival between the groups (p = 0.836 and p = 0.638, respectively). Among 381 non-sarcopenic patients, 48 patients (12.6%) were diagnosed as newly developed sarcopenia in one year after gastric resection. Compared with non-sarcopenic group, the newly developed sarcopenic group showed more male, more undifferentiated tumor, lower hemoglobin level, less alcoholic, less smoking, and presence of diabetes mellitus. However, there was no significant difference in the 5 - year overall survival and disease free survival among non-sarcopenic, sarcopenic, and newly developed sarcopenic groups (p = 0.521 and p = 0.534, respectively). The relationship between preoperative body fat volume and postoperative muscle mass showed a significant correlation (rho = 0.296, p &lt; 0.001), but only BMI was significantly associated with long term survival. Conclusions: Although newly developed sarcopenia after surgery did not affect the survival rate, patients with nutritional risk of sarcopenia after surgical resection may require early evaluation of nutritional status and nutritional support.
Effect of adding bevacizumab to chemotherapy on pathologic response to preoperative systemic therapy of potentially resectable colorectal cancer liver metastases (CLM): A systematic review and meta-analysis.
Authors: Alexandre A. Jácome, Fernanda A. Oliveira, Flora De Moraes Lino Silva, João Paulo da Silveira Nogueira Lima
Journal: Journal of Clinical Oncology (2020)

151 Background: Perioperative CT and resection of CLM are potentially curative therapies in the management of metastatic colorectal cancer (mCRC). Retrospective studies suggest that preoperative bevacizumab increases pathologic response, which is a surrogate endpoint for overall survival (OS). We conducted the first systematic review and meta-analysis addressing the effect of bevacizumab on pathologic response to preoperative therapy of CLM. Methods: We systematically searched PubMed, Cochrane Library, Embase and LILACS from January/2004 to August/2019 for studies that have compared the pathologic response to CT plus bevacizumab versus CT alone as preoperative therapy of potentially resectable CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoint was major response (MaR) (0-50% residual cancer cells or tumor regression grade (TRG) 1-3 in liver specimen). The likelihood of preoperative therapy being associated with pCR or MaR has been expressed by odds ratio (OR) and 95% confidence intervals (CI) using a random-effects model. Results: Of the 1,319 studies yielded by the search, 9 studies were retained, totaling 1,202 patients (516 CT plus bevacizumab versus 686 CT alone). The addition of bevacizumab to CT increased the pCR rate, but it did not reach statistical significance (OR: 1.24, 95% CI 0.81 – 1.92, p = 0.32). However, MaR was significantly superior in the bevacizumab group (OR: 2.20, 95% CI 1.47 – 3.29, p &lt; 0.001). A higher percentage of patients have been submitted to oxaliplatin-based regimens in bevacizumab group compared to CT alone group (84% versus 68%, p &lt; 0.001), while irinotecan-based regimens have been more common in the CT alone group (11% versus 28%, p &lt; 0.001). Conclusions: The addition of bevacizumab to preoperative CT was associated with higher rates of pathologic response in liver resection of CLM. Anti-angiogenics might potentially improve the recurrence-free survival and OS in the management of potentially resectable CLM and should be evaluated as preoperative therapy in randomized clinical trials.
The lymph node stromal laminin α5 shapes alloimmunity
Authors: Lushen Li, Marina W. Shirkey, Tianshu Zhang, Yanbao Xiong, Wenji Piao, Vikas Saxena, Christina Paluskievicz, Young Lee, Nicholas Toney, Benjamin M. Cerel, Qinshan Li, Thomas Simon, Kyle D. Smith, Keli L. Hippen, Bruce R. Blazar, Reza Abdi, Jonathan S. Bromberg
Journal: Journal of Clinical Investigation (2020)

Lymph node stromal cells (LNSCs) regulate immunity through constructing lymphocyte niches. LNSC-produced laminin α5 (Lama5) regulates CD4+ T cells but the underlying mechanisms of its functions are poorly understood. Here we show that depleting Lama5 in LNSCs resulted in decreased Lama5 protein in the LN cortical ridge (CR) and around high endothelial venules (HEVs). Lama5 depletion affected LN structure with increased HEVs, upregulated chemokines, and cell adhesion molecules, and led to greater numbers of Tregs in the T cell zone. Mouse and human T cell transendothelial migration and T cell entry into LNs were suppressed by Lama5 through the receptors α6 integrin and α-dystroglycan. During immune responses and allograft transplantation, depleting Lama5 promoted antigen-specific CD4+ T cell entry into the CR through HEVs, suppressed T cell activation, and altered T cell differentiation to suppressive regulatory phenotypes. Enhanced allograft acceptance resulted from depleting Lama5 or blockade of T cell Lama5 receptors. Lama5 and Lama4/Lama5 ratios in allografts were associated with the rejection severity. Overall, our results demonstrated that stromal Lama5 regulated immune responses through altering LN structures and T cell behaviors. This study delineated a stromal Lama5-T cell receptor axis that can be targeted for immune tolerance modulation.
Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial
Authors: Marina C Garassino, Shirish Gadgeel, Emilio Esteban, Enriqueta Felip, Giovanna Speranza, Manuel Domine, Maximilian J Hochmair, Steven Powell, Susanna Yee-Shan Cheng, Helge G Bischoff, Nir Peled, Martin Reck, Rina Hui, Edward B Garon, Michael Boyer, Ziwen Wei, Thomas Burke, M Catherine Pietanza, Delvys Rodríguez-Abreu
Journal: The Lancet Oncology (2020)
Impact of palliative care in patients with metastatic esophageal cancer declining chemotherapy.
Authors: Nicholas Manguso, Sungjin Kim, Michelle Guan, Veronica Placencio-Hickok, Haesoo Kim, Jar-Yee Liu, Andrew Eugene Hendifar, Samuel J. Klempner, Miguel Burch, Alexandra Gangi, Joseph Chao, Mitchell Kamrava, Katelyn Mae Atkins, Jun Gong
Journal: Journal of Clinical Oncology (2020)

315 Background: Palliative care has been associated with improved overall survival (OS), but limited data exist in metastatic esophageal cancer (mEC). We investigated the impact of palliative care in patients with mEC who declined chemotherapy (CTX). Methods: The National Cancer Database was used to identify patients between 2004-2015. Patients with M1 disease who declined CTX and had known palliative care status (surgery, radiotherapy [RT], pain management, or any combination of) were included. Cases with unknown CTX, RT, or nonprimary surgery status were excluded. Kaplan-Meier estimates of OS were calculated. Univariable and multivariable Cox regressions were performed. Results: Among 140,234 EC cases, we identified 1,493 patients who declined CTX and had complete data. Median age was 70 years, most (66.3%) had a Charlson Comorbidity Index (CCI) of 0, and 37.1% were treated at an academic center. Most (72.7%) did not receive palliative care. Median OS was 2.53 months (mos), with no statistically significant difference in median OS between those receiving palliative care (2.83 mos, 95% confidence interval [CI] 2.53-3.12) vs. no palliative care (2.37 mos, 2.2-2.56; p = 0.288). On univariable analysis, treatment at an academic center (hazard ratio [HR] 0.90, 0.80-1.00) and CCI ≥2 (HR 1.20, 1.00-1.42) were predictive of OS (p &lt; 0.05). On multivariable analysis, male sex (HR 1.23, 1.08-1.40), South geographic region (HR 1.23, 1.04-1.46), CCI of 1 (HR 1.17, 1.03-1.32), higher grade (HR 1.21, 1.07-1.38), and higher T stage (HR 1.39, 1.12-1.73) were associated with poor OS (p &lt; 0.05). Conclusions: Palliative care conferred a numerically higher, but not statistically significant difference in OS among patients with mEC declining CTX. Quality of life metrics, inpatient status, and subgroup analyses are important for examining the role of palliative care in mEC and future studies are warranted.
Clinical Advances in Sex- and Gender-Informed Medicine to Improve the Health of All
Authors: Deborah Bartz, Tanuja Chitnis, Ursula B. Kaiser, Janet W. Rich-Edwards, Kathryn M. Rexrode, Page B. Pennell, Jill M. Goldstein, Mary Angela O’Neal, Meryl LeBoff, Maya Behn, Ellen W. Seely, Hadine Joffe, JoAnn E. Manson
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> Biological sex and sociocultural gender represent major sources of diversity among patients, and recent research has shown the association of sex and gender with health. A growing body of literature describes widespread associations of sex and gender with cells, organs, and the manner in which individual patients interact with health care systems. Sex- and gender-informed medicine is a young paradigm of clinical practice and medical research founded on this literature that considers the association of sex and gender with each element of the disease process from risk, to presentation, to response to therapy. <h3>Observations</h3> Characteristics that underlie sex and gender involve both endogenous and exogenous factors that change throughout the life course. This review details clinical examples with broad applicability that highlight sex and gender differences in the key domains of genetics, epigenomic modifiers, hormonal milieu, immune function, neurocognitive aging process, vascular health, response to therapeutics, and interaction with health care systems. These domains interact with one another in multidimensional associations, contributing to the diversity of the sex and gender spectra. Novel research has identified differences of clinical relevance with the potential to improve care for all patients. <h3>Conclusions and Relevance</h3> Clinicians should consider incorporating sex and gender in their decision-making to practice precision medicine that integrates fundamental components of patient individuality. Recognizing the biological and environmental factors that affect the disease course is imperative to optimizing care for each patient. Research highlights the myriad ways sex and gender play a role in health and disease. However, these clinically relevant insights have yet to be systematically incorporated into care. The framework described in this review serves as a guide to help clinicians consider sex and gender as they practice precision medicine.
Advances in the Treatment of Acute Myeloid Leukemia: New Drugs and New Challenges
Authors: Nicholas J. Short, Marina Konopleva, Tapan M. Kadia, Gautam Borthakur, Farhad Ravandi, Courtney D. DiNardo, Naval Daver
Journal: Cancer Discovery (2020)

Abstract The therapeutic armamentarium of acute myeloid leukemia (AML) has rapidly expanded in the past few years, driven largely by translational research into its genomic landscape and an improved understanding of mechanisms of resistance to conventional therapies. However, primary and secondary drug resistance remains a substantial problem for most patients. Research into the mechanisms of resistance to these new agents is informing the development of the next class of AML drugs and the design of combination regimens aimed at optimally exploiting therapeutic vulnerabilities, with the ultimate goal of eradicating all subclones of the disease and increasing cure rates in AML. Significance: AML is a heterogeneous disease, characterized by a broad spectrum of molecular alterations that influence clinical outcomes and also provide potential targets for drug development. This review discusses the current and emerging therapeutic landscape of AML, highlighting novel classes of drugs and how our expanding knowledge of mechanisms of resistance are informing future therapies and providing new opportunities for effective combination strategies.
Comparing total cost of care for Medicare FFS patients with pancreatic cancer by chemotherapy regimen.
Authors: Jared Hirsch, Gabriela Dieguez, Paul Cockrum
Journal: Journal of Clinical Oncology (2020)

e19394 Background: To analyze total cost of care for patients with pancreatic cancer by common therapeutic regimens. Methods: Cancer episodes were identified using a methodology similar to the Medicare Oncology Care Model (OCM) in the 2014-2016 100% Medicare Limited Data Set (LDS) claims files. Index dates for chemotherapy claims could not occur within 6 months of another chemotherapy claim for all Medicare FFS beneficiaries. Cancer episodes were defined as the 6-month period following an index date. Each episode was assigned a cancer type based on the plurality of cancer ICD 9/10 diagnosis codes that occurred on chemotherapy claims in the episode. Episode costs were calculated from claims paid amounts. DME and other Part B spending was estimated using episodes from the 5% Medicare LDS files using the same methodology. We analyzed total episode costs for five pancreatic cancer treatment regimens: gemcitabine plus nab-paclitaxel (gem-nab), FOLFIRINOX, liposomal irinotecan, FOLFOX, and FOLFIRI. Results: We identified 110,618 cancer episodes in 2016, of which 4,018 were pancreatic cancer. Pancreatic cancer patients in these episodes were treated with gem-nab (45% of episodes), FOLFIRINOX (14%), FOLFOX (8%), FOLFIRI (6%), and liposomal irinotecan (4%). The main drivers of episode costs among regimens were Part B chemotherapy, other Part B drugs, and inpatient services. Episode costs were $41,749, $42,086, $35,601, $36,169, and $45,851 for patients receiving gem-nab, FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan, respectively. Part B chemotherapy costs were $13,065 (gem-nab), $3,095 (FOLFIRINOX), $4,853 (FOLFOX), $3,204 (FOLFIRI), and $18,474 (liposomal irinotecan); other Part B drug costs were $7,343 (gem-nab), $17,013 (FOLFIRINOX), $11,131 (FOLFOX), $15,377 (FOLFIRI), and $10,479 (liposomal irinotecan); and inpatient service costs were $9,044 (gem-nab), $9,069 (FOLFIRINOX), $7,701 (FOLFOX), $5,838 (FOLFIRI), and $5,108 (liposomal irinotecan). Conclusions: Total episode costs for pancreatic cancer care ranged from $35,601 (FOLFOX) to $45,851 (liposomal irinotecan), but the cost components varied by regimen. Episodes with liposomal irinotecan had the largest Part B chemotherapy costs but the lowest inpatient service costs. Episodes with FOLFIRINOX and gem-nab had similar inpatient service costs, which were higher than episodes with liposomal irinotecan, FOLFOX, or FOLFIRI. Episodes with FOLFIRINOX and FOLFIRI had higher other Part B drug costs than episodes with FOLFOX, liposomal irinotecan, or gem-nab.
Neuronal mitochondria-targeted micelles relieving oxidative stress for delayed progression of Alzheimer's disease
Authors: Peng Yang, Dongyu Sheng, Qian Guo, Pengzhen Wang, Shuting Xu, Kang Qian, Yixian Li, Yunlong Cheng, Liuchang Wang, Wei Lu, Qizhi Zhang
Journal: Biomaterials (2020)
Immunotherapy versus biologics as second-line therapy in advanced hepatocellular carcinoma (HCC).
Authors: Mohammed Al-Jumayli, Hannah Hildebrand, Saqib Abbasi, Anup Kasi, Anwaar Saeed
Journal: Journal of Clinical Oncology (2020)

533 Background: Sorafenib or lenvatinib are the current frontline options for advanced HCC. Multiple biologic agents including multi-Tyrosine Kinase Inhibitors (TKI) cabozantinib &amp; regorafenib have been recently approved for the previously treated population. Immunotherapy (IO) agent Nivolumab have also been approved in the same setting. Due to lack of prospective head to head comparison, there is no standardized way for alternating those agents beyond frontline. Methods: We performed a retrospective review of KU cancer registry. Patients with advanced HCC were divided into 2 groups based on the 2nd line systemic regimen (IO vs non-IO). Kaplan–Meier and Cox proportional hazards models were utilized to evaluate progression free survival (PFS) and overall survival (OS). Results: Between 2016-2019, 98 patients were identified, 41 received IO, while 57 received biologics. All patients had sorafinib as 1st line therapy. Most patients have ECOG 0-1 and Child-Pugh class A or B. 55% had hepatitis C, 6% hepatitis B and 27 % have history of alcohol misuse. Almost 50% of patients have received prior liver directed therapy. Comparing IO vs non-IO groups, median PFS was 3.9 months vs 3 months and median OS was 10 months vs 10 months. There was no statistically significant difference in PFS &amp; OS but there was a delay separation in the survival curve favoring IO. Similar outcome was seen in a sub-group analysis of the hepatitis C patients. Conclusions: This retrospective comparative review of current 2nd line regimens is one of the first &amp; largest studies reported. In this study population, IO was not superior to multi-TKI as a 2nd line regimen. The late survival curve separation favoring IO might suggest a delay IO effect in a subgroup of patients. Future studies should define specific biomarkers that could predict response and allow treatment to be optimized depending on patient and tumor characteristics. Furthermore, combining IO plus multi-TKI might be a promising next step in development. A number of ongoing trials are testing this strategy including our CAMILLA trial of Cabozantinib plus Durvalumab, currently enrolling patients at the University of Kansas Cancer Center NCT03539822 .
Exosomes mediate sensory hair cell protection in the inner ear
Authors: Andrew M. Breglio, Lindsey A. May, Melanie Barzik, Nora C. Welsh, Shimon P. Francis, Tucker Q. Costain, Lizhen Wang, D. Eric Anderson, Ronald S. Petralia, Ya-Xian Wang, Thomas B. Friedman, Matthew J.A. Wood, Lisa L. Cunningham
Journal: Journal of Clinical Investigation (2020)

Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non–cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell–specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss.
Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema
Authors: Thibault Mahévas, Bertrand Arnulf, Jean-David Bouaziz, Cristina Bulai Livideanu, Amélie Osio, Amandine Servy, Bernard Cribier, Bruno Sassolas, Marie Jachiet, Laurence Michel, Pierre Aucouturier, Dan Lipsker, Camille Frances, Emilie Sbidian, Michel Rybojad, Vincent Descamps, Michel D'Incan, Philippe Humbert, Marie Beylot-Barry, Thierry Passeron, Claire de Moreuil, Ruba Y Taha, Olivier Hermine, Alain Dupuy, Sébastien Barbarot, Sebastien Debarbieux, Olivier Carpentier, Fanny Brault, Jean-Luc Schmutz, Domitille Thomas-Beaulieu, Philippe Modiano, Charles Zarnitsky, Francois Lifermann, Emilie Baubion, Nicolas Limal, Fabien Le Bras, Marie Le Moigne, Marie Tauber, Alexis Talbot, Romain Prud'homme, Sandy Peltier, Adele de Masson, Maxime Battistella, Martine Bagot, Arsène Mékinian, Olivier Fain
Journal: Blood (2020)
Patterns of failure after adjuvant stereotactic body radiation therapy in patients with pancreatic cancer with close or positive margins.
Authors: Ankur Patel, Joshua L. Rodríguez-López, Nathan Bahary, Amer H. Zureikat, Steven A. Burton, Dwight Earl Heron, Adam C. Olson
Journal: Journal of Clinical Oncology (2020)

755 Background: There is no consensus on treatment volumes for stereotactic body radiation (SBRT) in patients with pancreatic cancer (PCa). Herein, we report patterns of failure following adjuvant SBRT for close/positive margins in patients with pancreatic cancer, which may inform appropriate target volume design for SBRT. Methods: An IRB-approved retrospective review of patients with PCa treated with adjuvant SBRT for close/positive margins from 2009-2018 was conducted. Patterns of failure were assessed by review of imaging and were defined as local (LF), regional (RF), local and regional (LRF), or distant (DF). The Kaplan-Meier method was used to calculate long-term failure rates. In-field failures were defined as LFs completely within the PTV (planning target volume). The location of LFs was compared to the RTOG consensus volumes for adjuvant treatment of PCa to determine if conventional radiation volumes would have included the LF. Results: Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins, with a median follow-up of 17.0 months (interquartile range [IQR] 7.4-28.3 mos.). Adjuvant SBRT was delivered at a median of 2.2 months after surgery (IQR 1.7-3.0 mos.). Most patients (81.6%) received 36 Gy in 3 fractions. The median PTV volume was 17.8 cc (IQR 12.3-25.2 cc). Upon examination of first failure sites, crude rates of isolated LF, isolated RF, isolated LRF, and DF +/- LF or RF were 9.2%, 6.6%, 2.6%, and 56.6% respectively; 2-year rates were 12.4%, 11.5%, 7.0%, and 66.5%, respectively. Thirty-two patients (42.1%) developed a LF at some point during follow-up. Of 28 LFs with available plans and imaging, 21.4% were in-field failures, while the remainder were completely outside (60.1%) or partially outside (17.9%) the PTV. Most LFs outside the PTV (90.9%) would have been encompassed by the RTOG consensus target volumes for postoperative conventional radiation. Conclusions: In patients with PCa who receive adjuvant SBRT for close/positive margins, the majority of LFs are outside the PTV. Future trials involving SBRT or hypofractionated radiation should consider expansion of treatment volumes if feasible.