tbuckley/cabot-search huggingface dataset:
Differences in body composition between patients with early or metastatic breast cancer (BC).
Authors: Shlomit Strulov Shachar, Allison Mary Deal, Marc Weinberg, Grant Richard Williams, Kirsten A Nyrop, Seul Ki Choi, Julia M. Benbow, Hyman B. Muss
Journal: Journal of Clinical Oncology (2017)

e21707 Background: There is growing evidence in oncology that skeletal muscle (SM) loss, known as sarcopenia, can be identified from routine computed tomography (CT) imaging and used to predict increased chemotherapy toxicity, mortality, and other adverse clinical outcomes (Shachar-EJC, 2016, Shachar-CCR, 2016). The contributions of age-related and cancer-related loses in SM at diagnosis remains poorly understood. This study compares CT-derived measures of SM at the time of diagnosis in patients with early BC (EBC) versus metastatic BC (MBC) patients to investigate the impact of metastatic cancer on SM. Methods: Body composition measures were compared between patients with EBC receiving adjuvant chemotherapy and MBC initiating first line palliative chemotherapy. Measures were derived from analysis CT scans of L3 lumbar segments using radiological software (ABACS). Measures include: skeletal muscle area (SMA), density (SMD), index (SMI = SMA/height ^2), and integrated density (SMID = SMI x SMD). Sarcopenia was defined as SMI &lt; 41(Martin-JCO, 2013). Lean body mass (LBM) was calculated (kg) = [(L3 Muscle measured by CT (cm2) × 0.3) + 6.06]) (Prado-CCR, 2009). Body surface area (BSA) was calculated using the Mosteller formula. T-tests (continuous) and Chi-squared tests (categorical) compared variables between groups; multivariable linear regression models controlled for age and body mass index (BMI). Results: MBC patients (n = 40) were older than EBC (n = 151) (56 vs 49 years, p &lt; 0.001). Mean BMI and BSA were similar in both groups (29.0 vs 28.8, p = 0.84; 1.87 vs 1.86 m 2 , p = 0.55). After adjusting for age and BMI, SMI (41.3 vs 44.7 cm 2 /m 2 , p = 0.009), SMD (29.8 vs 36.4 Hounsfield Units, p &lt; 0.0001), SMG (1250 vs 1612, p &lt; 0.0001), and LBM (39.3 vs 41.9 kg, p = 0.024) were significantly lower in the MBC group. The MBC group included significantly more sarcopenic patients (58% vs 31%, p = 0.0016). Conclusions: Although BMI and BSA were similar in EBC and MBC patients, SM measures showed significant differences. MBCs had lower LBM, SMI, and SMD. More advanced BC was associated with higher proportions of sarcopenia. Further research is needed to explore interventions in sarcopenic patients in order improve outcomes in women with both EBC and MBC.
Assessment of nutritional and inflammatory status to determine the prevalence of malnutrition in patients undergoing surgery for colorectal carcinoma.
Authors: Antonella Daniele, Rosa Divella, Addolorata Casamassima, Raffaele De Luca, Eustachio Ruggieri, Cosimo Caliandro, Anna Atlante, Francesco Giotta, Ines Abbate
Journal: Journal of Clinical Oncology (2016)

e15091 Background: Cancer disease is often associated with protein-caloric malnutrition that affects 8% to 84% of patients. Cancer-Related Anorexia-Cachexia Syndrome (CACS), is characterized by a negative protein balance and energy caused both by a reduced caloric intake from both metabolic abnormalities associated with loss of muscle mass with or without loss of mass fat, considerable weight loss and increased proinflammatory cytokines and/or inflammatory markers. It is estimated that about 20% of all cancer deaths occur for malnutrition. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma and 30 patients with benign colon disease. Methods: Nutritional Statuswere assessment by Mini Nutritional Assessment (MNA), serum levels of Interleuchin-6, Tumor Necrosis Factor-α and adiponectina by enzyme-linked immunoassorbent assay while C-Reactive Protein and Transferrin were tested using chemiluminescent immunometric assay. Results: The MNA mean score in colorectal patients was 26.2 ± 13.2; 23/78 patients (29,4%) presented a state nutritional normal 36/78 (46.1%) reported a risk of malnutrition while 19/78 (24.3%) were malnourished; all malnourished patients had in the previous six months from the date of diagnosis, a significant weight loss ( > 10 kg), muscle mass loss and severe reduction in the intake of food due loss of appetite and altered taste perception. Besides serum mean of IL-6, TNF-α PCR, and adiponectin were significantly higher in colorectal patients respect to control group (p < 0.001, p < 0.0001, p < 0.0001, and p < 0.0001 respectively) while an decrease of TRF levels in cancer patients vs benign disease patients (p < 0.0001) was found. Conclusions: more than 50% of cancer patients were malnourished or at risk of malnutrition so they needed nutritional intervention before and during chemotherapy in order to improve the response to treatment, and their quality of life.
A pilot study of omalizumab to reduce the incidence of oxaliplatin-induced hypersensitivity reaction (HSR): An interim analysis.
Authors: Stacey Stein, Nataliya Volodymyrivna Uboha, Kirsten Dooley, Howard S. Hochster
Journal: Journal of Clinical Oncology (2018)

e15555 Background: : Oxaliplatin (OX) HSR occur and can limit an effective therapy in pts with GI malignancies, particularly on re-treatment. The mechanism of HSR is thought to be mediated via IgE dependent activation of mast cells and subsequent release of preformed inflammatory mediators. Omalizumab is a human anti-IgE Ab that inhibits IgE binding to its high affinity receptor on mast cells and basophils. This study sought to examine whether Omalizumab reduces the rate of OX HSR in pts who have had a prior mild/moderate HSR to OX. Methods: Pts with clinically evident HSR to OX (without bronchospasm) despite prior pre-medication, and with stage IV GI cancer appropriate for further OX were eligible to enroll. Pts received omalizumab (300 mg subq) every 2 weeks during the duration of OX containing chemotherapy, starting 7 days before OX-based therapy (given alternate weeks q2w). All pts received Zyrtec, Benadryl, and dexamethasone on the evening before and morning of treatment. Results: : Nine pts enrolled out of a planned accrual of 12 pts. All pts had colon cancer. There were no side effects from Omalizumab, including HSR or local skin reactions. 9 pts had received standard premedication, 1 dilutional densistization and 1 in-patient desensitization prior to study. Prior to starting Omalizumab pts were rechallenged once (1 pt), 2 twice (5 pts and 5 times (1 pt) with reaction. Six pts were able to receive 5 or more additional cycles of OX on study. One pt remains on study, currently receiving 5th cycle. Only 1 pt came off study with an OX HSR on the first cycle. The other 6 pts came off of study secondary to progression, neuropathy, or patient choice. One pt received 10 doses on study and stopped OX for grade 2 mucositis and grade 2 peripheral neuropathy. One pt received 8 cycles and came off for progression of disease and later went back on the study approximately 7 months later but had a reaction with the first dose of OX. The median number of cycles using Omalizumab was 5 cycles (range 1-10). Conclusions: Omalizumab is a promising drug for abrogating OX HSR and allows additional treatment for pts with a prior mild/moderate HSR, and should be studied further. Clinical trial information: NCT02266355.
TCT-685 The improvement of left ventricular function after CTO revascularization—a strain echocardiography based study
Authors: Chun Kai Chen, Zheng Wei Chen, Chih Fan Yeh, Ching-Chang Huang, Mao-Shin Lin, Ying-Hsien Chen, Lung-Chun Lin, Paul Hsien-Li Kao
Journal: Journal of the American College of Cardiology (2018)
Impact of skeletal muscle index (SMI) loss during palliative systemic treatment (Tx) on time to progression and overall survival (OS) in metastatic colorectal cancer (mCRC) patients.
Authors: Sophie Kurk, Petra H.M. Peeters, Rebecca K. Stellato, Bram Dorresteijn, Marion Jourdan, Geert-Jan Creemers, Frans Erdkamp, Felix E. de Jongh, Petrus Alouisius Maria Kint, Boelo Jan Poppema, Sandra Anita Radema, Lieke H Simkens, Bea Tanis, Manuel Lucien Roy Tjin-A-Ton, Ankie Van Der Velden, Cornelis J. A. Punt, Miriam Koopman, Anne Maria May
Journal: Journal of Clinical Oncology (2017)

10087 Background: Evidence for a strong link between skeletal muscle depletion and poor outcomes in mCRC is growing. However, the impact of SMI changes over time on progression and OS during palliative systemic Tx is not known. The CAIRO3 study (Simkens et al. Lancet 2015) randomized 556 mCRC patients after 6 cycles capecitabine+oxaliplatin+bevacizumab (CAPOX-B) to maintenance CAP-B Tx (Main) vs. observation (Obs). Upon 1 st disease progression (PD1), CAPOX-B or other treatment was reintroduced until 2 nd disease progression (PD2). This is the first analysis using scan data of multiple time-points to investigate SMI changes during palliative systemic treatment Tx and its association with survival. Methods: 1227 CT-scans of a random selection of 416 CAIRO3 patients (mean age 64±9 years, Main n = 206; Obs n = 210) were analyzed for SMI (skeletal muscle area at the L3 level in cm 2 /m 2 ). Using mixed model analysis, SMI changes were analyzed for two intervals; interval 1: from randomization to PD1, and interval 2: from PD1 to PD2. Three Cox regression models were used to study the association between SMI loss and time to PD2 and death for interval 1, and time to death for interval 2. Main and Obs groups were combined in the analyses since the p-value for interaction was not significant. Hazard ratios (HR) were reported per 2 units change in SMI. Results: Median times from randomization to PD1, PD2 and death were 7.7, 13.5 and 24 months resp. During interval 1 (less intensive or no Tx) patients gained SMI on average (1.2 units; 95%CI 0.6-1.8), but 23% of patients still lost SMI. SMI loss was associated with shorter time to PD2 (HR 0.88; 0.81-0.98, p= .01), but not with shorter OS (HR 0.94; 0.86-1.02, p= .17). During interval 2 (more intensive Tx) average SMI loss was -2.2 units ( 1.5-2.8) and 63% of patients lost SMI. SMI loss was associated with shorter OS (HR 0.73; 0.62-0.86, p&lt; .00). Conclusions: Loss of SMI was related to shorter time to progression during first line less intensive main Tx or obs and shorter overall survival during more intensive reinduction Tx. This large longitudinal study suggests that SMI preservation may be a therapeutic goal. Clinical trial information: NCT00442637.
TCT-304 Long term clinical outcomes in acute coronary syndrome patients at high bleeding risk undergoing PCI with implantation of everolimus-eluting stents: Results from the Patient-Level Pooled Analysis of EES Post Approval Studies.
Authors: None Paul Guedeney, Sabato Sorrentino, Bimmer Claessen, Usman Baber, Birgit Vogel, Mitchell Krucoff, Ken Kozuma, Junbo Ge, Ashok Seth, Raj Makkar, Sripal Bangalore, Deepak Bhatt, Dominick Angiolillo, Vinuta Rau, Shigeru Saito, Franz-Josef Neumann, James Hermiller, Marco Valgimigli, Roxana Mehran
Journal: Journal of the American College of Cardiology (2018)
Mutational burden and activated T cell infiltration in lung squamous cell carcinomas with DNA repair mutations.
Authors: Young Kwang Chae, Jonathan Forrest Anker, Nisha Anjali Mohindra, Jason B. Kaplan, Sunandana Chandra, Benedito A. Carneiro, Maria Matsangou, Victoria Meucci Villaflor, Leonidas C. Platanias, Francis J. Giles
Journal: Journal of Clinical Oncology (2016)

3042 Background: Mutations in DNA repair genes are common in cancer, and may induce a state of hypermutability. Importantly, mutational burden is linked to enhanced response to immunotherapies, as potentially immunogenic neo-antigens may drive a stronger anti-tumor immune response. Methods: We utilized mutation (n = 178) and mRNA expression (n = 501) data from the TCGA database for lung squamous cell carcinoma to analyze the link between DNA repair mutations, mutational burden, and predicted immune cell type tumor infiltration using a defined list of “immune metagenes” (Angelova et al,2015). Results: Tumors were infiltrated most by activated CD4 (36.1%) and CD8 (28.1%) T cells (top 9 of 28 total immune cell types listed in Table 1). This was further pronounced in tumors with higher mutational burden displaying an increase in activated CD4 and CD8 T cells (p < 0.05). Additionally, tumors with 0, 1, or 2-4 mutated homologous recombination (HR) DNA repair genes contained 221, 355, and 521 mutations, respectively. Those with 0, 1, or 2-3 mismatch repair (MMR) genes displayed mutation counts of 235, 341, and 786, respectively. Interestingly, tumors with HR mutations had increased infiltration by neutrophils, while those with MMR mutations were infiltrated by activated CD4 and activated CD8 T cells. Conclusions: Overall, mutational burden was linked to increased activated CD4 and CD8 T cells, and DNA repair mutations were linked to increased mutational burden. However, only MMR mutations were associated with activated CD4 and CD8 T cell infiltration, and may better serve as biomarkers to predict patient response to immunotherapy. Immune cell type Percent of patients with infiltrations (%) Activated CD4 36.1 Activated CD8 28.1 Effector memory CD4 10.6 γδ T cells 9.6 Mature dendritic cells (DCs) 7.0 Th17 T cells 5.8 DCs 5.0 Monocytes 4.8 NK cells 4.8 *Anker and Chae contributed equally to this work
The Absence of the ACE N-Domain Decreases Renal Inflammation and Facilitates Sodium Excretion during Diabetic Kidney Disease
Authors: Masahiro Eriguchi, Ellen A. Bernstein, Luciana C. Veiras, Zakir Khan, Duo Yao Cao, Sebastien Fuchs, Alicia A. McDonough, Jorge E. Toblli, Romer A. Gonzalez-Villalobos, Kenneth E. Bernstein, Jorge F. Giani
Journal: Journal of the American Society of Nephrology (2018)

Background Recent evidence emphasizes the critical role of inflammation in the development of diabetic nephropathy. Angiotensin-converting enzyme (ACE) plays an active role in regulating the renal inflammatory response associated with diabetes. Studies have also shown that ACE has roles in inflammation and the immune response that are independent of angiotensin II. ACE’s two catalytically independent domains, the N- and C-domains, can process a variety of substrates other than angiotensin I. Methods To examine the relative contributions of each ACE domain to the sodium retentive state, renal inflammation, and renal injury associated with diabetic kidney disease, we used streptozotocin to induce diabetes in wild-type mice and in genetic mouse models lacking either a functional ACE N-domain (NKO mice) or C-domain (CKO mice). Results In response to a saline challenge, diabetic NKO mice excreted 32% more urinary sodium compared with diabetic wild-type or CKO mice. Diabetic NKO mice also exhibited 55% less renal epithelial sodium channel cleavage (a marker of channel activity), 55% less renal IL-1 β , 53% less renal TNF- α , and 53% less albuminuria than diabetic wild-type mice. This protective phenotype was not associated with changes in renal angiotensin II levels. Further, we present evidence that the anti-inflammatory tetrapeptide N-acetyl-seryl-asparyl-lysyl-proline (AcSDKP), an ACE N-domain–specific substrate that accumulates in the urine of NKO mice, mediates the beneficial effects observed in the NKO. Conclusions These data indicate that increasing AcSDKP by blocking the ACE N-domain facilitates sodium excretion and ameliorates diabetic kidney disease independent of intrarenal angiotensin II regulation.
Use of percutaneous endoscopic gastrostomy (PEG) tube feeding support in head and neck cancer patients.
Authors: Ramla Namisango Kasozi, Anita Choudhary, Kelly Andrus, Richard C.K. Wong, Rory Eric Randall, Catherine Marie Orovets, Gurvinder Bali, Lilit Karapetyan, Michael K. Gibson, Ping Fu, Jesse Sloan
Journal: Journal of Clinical Oncology (2018)

e18062 Background: Insertion of percutaneous endoscopic gastrostomy (PEG) tubes for enteral feeding in patients with head and neck squamous cell carcinoma (HNSCC) undergoing multimodality therapy is often utilized to provide nutritional support in this at-risk population. The primary objective of our study was to review data regarding PEG tube placement at our in order to determine baseline factors that could assist in choosing pre- versus during-treatment PEG placement. Maintaining a weight loss decrease of < 10% of initial body weight was deemed success from PEG use. Methods: We reviewed charts of all HNSCC patients treated with radiation and chemo-radiotherapy from 01/01/2012 to 12/31/2014. Data extracted: demographics, HNSCC type, stage, diagnosis date, treatment modality, swallowing function, date of PEG placement and removal, duration of PEG insertion, ECOG PS, weight, and p16. Statistical tests used: Chi-square, Fisher exact test, T-tests and ANOVA. Results: Demographics of 54 patients: 39 M/15 F; median age 62.5yrs; tumor location oropharynx 35/54 = 64.8%, oral cavity 9/54 = 16.7%, larynx 5/54 = 9.3%, nasopharynx 4/54 = 7.4%, and hypopharynx 3/54 = 5.6%. AJCC stage distribution upon diagnosis: stage 4 - 40/54 = 74.1%; stage 3 – 7/54 = 13.0%; stage 2-5/54 = 9.3%; and stage 1-2/54 = 3.7%. Treatment: CRT 27/45 = 50%, surgery+adjuvant CRT 11/54 = 20.4%, surgery+RT 9/54 = 16.7%, and RT alone 7/54 = 13.0%. The total rate of PEG usage was 87.0% (47/54) with 95% CI 0.76 -0.94. Time of PEG placement: pre-treatment 28/54 = 51.9%; during treatment 17/54 = 31.5%; and after treatment 2/54 = 3.7%. Swallow function results were not frequently recorded. From 12 patients, the mean aggregate difference of weight (95% CI) (pre-PEG – post-PEG) was negative 18.5 (9.9, 27.2) lbs, which is a 10.3% (18.5/178.9) decrease. Chi-square test association between cancer type and PEG tube placement was p= 0.026. Conclusions: Our study demonstrated in this varied population that pre-treatment PEG tube placement was able to prevent treatment related weight loss of > 10% initial body weight.The data suggests that prophylactic PEG use in the management of HNSCC patients treated with multimodality therapy reduced weight loss.
Identification of radiation induced exosomes as a potential i<i>n situ</i> vaccine for melanoma growth delay.
Authors: Mohammad Khurram Khan, Kishore Kumar Jella, Tahseen Nasti, Zhentian Li, David H. Lawson, Rafi Ahmed, William Dynan
Journal: Journal of Clinical Oncology (2018)

e21535 Background: The abscopal (literally, "out of field") effect is seen when radiotherapy targeted to one tumor site causes regression of distant metastases. The abscopal effect may be the clinical analog of the bystander effect, in which irradiated cells induce a radiation response-like effect in their non-irradiated neighbors. The bystander effect is in part mediated by exosomes. The objective of the current pre-clinical study was to determine whether exosomes from irradiated melanoma cells or tumors evoke radiation-like effects at nearby or distant (abscopal) sites, thereby contributing to tumor control. Methods: We developed a syngeneic mouse melanoma model to study the radiation-induced abscopal effect and the impact of irradiated melanoma cell exosomes in anti-tumor settings. Expansion of CD8 and CD4 T cells were monitored in both irradiated and non-irradiated, contralateral sites. Separately, exosomes were isolated from post-irradiated melanoma cells and tumors. They were characterized for protein content and for biological properties, including their ability to promote maturation and activation of dendritic cells and to induce melanoma growth delay. Results: In the mouse model, irradiation at one tumor site controlled tumor growth both locally and at an out-of-field (contralateral) site. This abscopal effect was correlated to an 11-fold increase in tumor infiltrating, antigen specific CD8 T cells at the irradiated site and a 4-fold increase at the contralateral, non-irradiated site. Exosomes isolated from post-irradiated melanoma cells were shown to contain key damage associated molecular patterns (DAMPs). These exosomes promote maturation and activation of splenic dendritic cells as evidenced by increases in CD80, CD86, PD-L1, and CD40 markers. Intratumoral injection of exosomes from irradiated cells or tumors significantly delayed tumor growth at the injected but not contralateral tumor in the in vivo engraftment model. Conclusions: Exosomes can transfer the anti-tumor effects of therapeutic radiation. Results establish a foundation for further pre-clinical and clinical studies to develop exosomes as an in situ vaccine for melanoma growth delay.
Heterogeneity of pediatric hepatocellular carcinoma.
Authors: Amber M D'Souza, Alexander Towbin, Alexander Bondoc, Anita Gupta, Jaimie Nathan, Maria Alonso, Greg Tiao, James I. Geller
Journal: Journal of Clinical Oncology (2018)

e22505 Background: Hepatocellular carcinoma (HCC) is an often chemoresistant neoplasm with a poor prognosis. Pediatric HCC may reflect unique biological and clinical heterogeneity. Methods: An IRB approved retrospective institutional review of HCC patients treated between 2004-2015 was undertaken. Results: 32 patients with HCC, median age 11.5 years (range 1-20) were identified. Pre-existing conditions included PFIC2 (2), Alagille (3), alpha-1 antitrypsin (1), Wilson’s disease (1), Fanconi anemia (2), cryptogenic cirrhosis (2), fatty liver disease (1), Fontan (1), Abernethy malformation (2), and portal venous thrombosis (2). Histology was conventional HCC (25; 9 with cirrhosis) and fibrolamellar HCC (7; 1 with cirrhosis). Evan’s staging was 1 (12); 2 (1); 3 (10); 4 (9). Evan’s stage in those with vs without a predisposition were 1 (8 vs 4), 2 (0 vs 1), 3 (6 vs 4) and 4 (3 vs 6). 16 patients underwent upfront surgical resection and 5 after neoadjuvant chemotherapy. Surgery included liver transplantation (LT, 11), hemihepatectomy (9), and segmentectomy (1). Other local control included Yttrium-90 radioembolization (4), radiofrequency ablation (RFA) (3), and abdominal radiation (1). 18 patients had medical therapy. Most common initial medical therapy included sorafenib alone (7) and cisplatin/doxorubicin based regimen (8; 3 with concurrent sorafenib). Overall, 14 (43.8%) survived with a median follow-up of 58.8 months (range 26.5-157.6). Cause of death was linked to lack of primary tumor surgery (11), Fanconi BMT complication (1), dialysis complication (1), progressive disease (subtotal resection) (1), and relapse (4). Of the survivors, Evan’s stage was 1 (11), 2 (1), and 3 (2, both treated with LT). 4/18 patients (22%) who received medical therapy survived. 9/17 with a predisposition are alive (53%). 8/11 (82%) who underwent LT remain alive. Conclusions: Various genetic and anatomic predisposing conditions were seen in over half of this pediatric HCC cohort and correlated with lower stage, adequate local control, and possibly survival. LT also associated with survival. Use of known chemotherapy agents may benefit a smaller group of pediatric HCC and warrants formal prospective study through cooperative group trials.