tbuckley/cabot-search huggingface dataset:
Breast cancer and incidence of non-caseating granulomas diagnosed in PET avid chest lymphadenopahy.
Authors: Rabih Bechara, Patricia Rich, Christopher Parks, Dacian Bonta, Ioana Bonta
Journal: Journal of Clinical Oncology (2017)

e12549 Background: Breast cancer is known to metastasize to the lung parenchyma and lymph nodes. Most breast malignancies are clinically staged using radiographic modalities (e.g. PET scans). Importantly, several inflammatory disorders will present lymph node FDG-uptake on PET, which can be mistaken for breast cancer metastasis. This may alter staging and implicitly treatment for individuals within whom both undiagnosed autoimmune disorders and breast cancer co-occur. We aim to examine the frequency of non-caseating granulomas diagnosed in PET avid mediastinal/hilar nodes in patients with known breast cancer. Methods: Between March 2013 and December 2015, 46 women diagnosed with breast cancer were staged by PET-CT. Those with positive result in the mediastinum/hilum underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis and ensuing treatment Results: Of the 46 patients with avid mediastinal/hilar adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had positive PET but negative cytology for malignancy. Twelve of the 15 patients with false positive PET had reactive lymph nodes, and 3 had non-caseating granulomas on cytology (see table). Twenty percent of the patients with negative cytology and positive PET had non-caseating granuloma, and 6.5 % of all patients with positive PET had non-caseating granulomas. Conclusions: To our knowledge, this study represents the largest cohort of breast cancer patients, where the incidence of non-caseating granulomas is investigated in PET-positive mediastinal/hilar nodes. We conclude that in selected patients, in addition to imaging, pathologic staging should be done. Also, the finding of non-caseating granulomas in these patients may either indicate an incidental diagnosis of early stage sarcoidosis, or an inflammatory reaction to the current treatment (sarcomatoid reaction). We also suggest that these patients should be followed for any manifestations of sarcoidosis. [Table: see text]
Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: An observational study
Authors: Clara Menendez, Paola Castillo, Miguel J. Martínez, Dercio Jordao, Lucilia Lovane, Mamudo R. Ismail, Carla Carrilho, Cesaltina Lorenzoni, Fabiola Fernandes, Tacilta Nhampossa, Juan Carlos Hurtado, Mireia Navarro, Isaac Casas, Paula Santos Ritchie, Sonia Bandeira, Sibone Mocumbi, Zara Jaze, Flora Mabota, Khátia Munguambe, Maria Maixenchs, Ariadna Sanz, Inacio Mandomando, Alfons Nadal, Anna Goncé, Carmen Muñoz-Almagro, Llorenç Quintó, Jordi Vila, Eusebio Macete, Pedro Alonso, Jaume Ordi, Quique Bassat
Journal: PLoS Medicine (2017)

Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed.In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction.The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.
The impact of a simplified documentation method for the Edmonton Classification System for Cancer Pain (ECS-CP) on clinician utilization.
Authors: Kimberson Tanco, Joseph Anthony Arthur, Ali Haider, Saneese Stephen, Sriram Yennu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

e21625 Background: The use of standardized pain classification systems such as the ECS-CP can assist in the assessment and management of cancer pain. However, its completion has been limited due to the perceived complexity of decoding the individual symbols of each feature. The objectives of this study were to determine the rate of clinician documentation and completion of the ECS-CP features after revision and simplification of the response for each feature. Methods: Electronic records of consecutive patient visits at the outpatient supportive care center seen by 12 palliative medicine specialists were collected during three study periods: 6 months before(pre-interventional period), 6 months and 24 months after (post-interventional period) the implementation of the simplified ECS-CP tool. Rate of ECS-CP documentation, completion, and analysis of patient and physician predictors were completed. Results: 1012 patients’ documentation was analyzed: 343 patients before, 341 six months after, and 328 twenty four months after the intervention. ≥ 2/5 items were completed before the intervention, 6 months after the intervention and 24 months after intervention in 0/343 (0%), 136/341 (40%), and 238/328 (73%) respectively [p < 0.001]. 5/5 items were completed before the intervention, 6 months after the intervention and 24 months after intervention in 0/343 (0%), 131/341 (38%), and 222/328 (68%) respectively [p < 0.001]. There were no patient or physician predictors found to be significant for successful documentation of ECS-CP features. Conclusions: Our findings suggest that significant simplification of the scoring system and intensive education is necessary for successful adoption of a scoring system. More research is needed in order to identify how to adopt tools for daily clinical practice in palliative care.
Intrapulmonary Transplantation of the Adenomatous Gastric Lesion of Strain I Mice
Authors: Howard B. Andervont, Michael B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1941)

Intrapulmonary Transplantation of the Adenomatous Gastric Lesion of Strain I Mice Get access Howard B. Andervont, Howard B. Andervont principal biologist Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael B. Shimkin Michael B. Shimkin assistant surgeon National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 2, October 1941, Pages 151–155, https://doi.org/10.1093/jnci/2.2.151 Published: 01 October 1941
Rethinking the Current American Joint Committee on Cancer TNM Staging System for Medullary Thyroid Cancer
Authors: Mohamed Abdelgadir Adam, Samantha Thomas, Sanziana A. Roman, Terry Hyslop, Julie A. Sosa
Journal: JAMA Surgery (2017)

Controversy exists around the American Joint Committee on Cancer (AJCC) TNM staging system for medullary thyroid cancer (MTC). Because of the rarity of the disease and limited available data, the staging system for MTC has been largely extrapolated from staging for differentiated thyroid cancer.To evaluate how well the current (seventh and eighth editions) AJCC TNM staging system correlates with survival for patients with MTC and to suggest a possible revision.This population-based retrospective cohort analysis used the National Cancer Database to select patients aged 18 years or older diagnosed with MTC in the United States between 1998 and 2012. Patient demographic and tumor characteristics were assessed, and pathologic tumor stages were provided as T, N, and M categories. Recursive partitioning with bootstrapping was used to divide patients by TNM stages into groups with similar survival. The newly identified groupings were validated in a Surveillance, Epidemiology, and End Results (SEER) cohort. Data analysis was conducted between July 17, 2016, and November 11, 2016.Overall survival and disease-specific survival.Of the 3315 patients with MTC included in the analysis, 1941 (58.6%) were women. The median (interquartile range) age was 54 (42-65) years, and 2839 (85.6%) self-reported their race/ethnicity as white. The current AJCC TNM staging system classified 941 of these patients (28.4%) as stage I, 907 (27.4%) as stage II, 424 (12.9%) as stage III, and 1043 (31.5%) as stage IV. Recursive partitioning analysis yielded 4 TNM groups: stage I (T1N0-1aM0, T2N0M0), stage II (T1N1bM0, T2N1a-bM0, and T3N0M0), stage III (T3N1a-bM0, T4N0-1bM0), and stage IV (T1-4N0-1bM1). Based on these proposed TNM groupings, 1797 of the 3315 patients (54.2%) were classified as stage I, 684 (20.6%) as stage II, 669 (20.2%) as stage III, and 165 (5.0%) as stage IV. Under the proposed TNM groupings, survival differences across TNM groups were more distinct than under the current AJCC TNM staging system. With stage I as the reference, the hazard ratios of the proposed TNM groupings and the current AJCC TNM staging system were 2.19 (95% CI, 1.37-3.12) vs 1.45 (95% CI, 1.09-1.92) for stage II, 4.20 (95% CI, 2.75-5.75) vs 2.17 (95% CI, 1.59-2.89) for stage III, and 10.97 (95% CI, 5.52-18.57) vs 5.33 (95% CI, 4.13-6.86) for stage IV. In a SEER cohort, the proposed TNM groupings were better at discriminating survival than was the current AJCC TNM staging system.The current AJCC TNM staging system for MTC appears to be less than optimal in distinguishing risk of mortality among stage groups, upstaging a significant number of patients to stage IV. The current AJCC TNM staging system could be improved with the new TNM groupings proposed here for more accurate risk stratification and potential treatment selection.
Familial seborrhoeic keratosis associated with multiple ‘pure reticulated acanthomas’ and infundibulocystic basal cell carcinomas
Authors: J. Agustí Martínez, R. Bella-Navarro, A.B. García-García, E. Bueno, R. González-Sarmiento, L. Navarro, B. Sanchez-Sendra, A. Revert, E. Jordá, C. Monteagudo
Journal: British Journal of Dermatology (2017)

A variety of genodermatoses with multiple cutaneous tumours and germline genetic alterations, such as PTCH1 mutations, have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis.
Calmodulin Mutants Linked to Catecholaminergic Polymorphic Ventricular Tachycardia Fail to Inhibit Human RyR2 Channels
Authors: Kafa Walweel, Nieves Gomez-Hurtado, Ye Wint Oo, Nicole A. Beard, Cris dos Remedios, Christopher N. Johnson, Walter J. Chazin, Dirk F. van Helden, Björn C. Knollmann, Derek R. Laver
Journal: Journal of the American College of Cardiology (2017)
A phase I study of the tolerability, safety, pharmacokinetics and preliminary antitumor effects of KBP-5209, a novel pan-HER inhibitor, in patients with advanced solid tumors.
Authors: Sarina Anne Piha-Paul, Sunil Sharma, Chengkon Shih, Bert H. O'Neil, Qinghong Zhou, Yuli Ding, Na Ou, Tingting Yu
Journal: Journal of Clinical Oncology (2017)

2565 Background: KBP-5209 is a novel potent and irreversible inhibitor of tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that preclinically has demonstrated potent antitumor activities in esophageal and gastric cancers and NSCLC. Methods: This first-in-human study (NCT02442414) was conducted to determine tolerability, safety, pharmacokinetics and antitumor activity of KBP-5209 administered QD or BID in patients (pts) with advanced solid tumors. Dose escalation (DE) initially was based on a modified accelerated titration plan and then shifted to a standard 3+3 design. The starting dose was 20 mg QD. Eligible patients were adults with advanced, refractory solid tumors with ECOG PS &lt; 1. A cycle was 28 days. DLTs were evaluated for during the first cycle. DE enriched for patients with tumors having molecular alterations in EGFR or HER2/3. Dose escalation continues so dose expansion has not initiated. Results: As of 26 Nov, 2016, 23 pts (15 females, 8 males) are a part of the evaluable population with a median age 57 (37-79) treated at doses of 20mg (1), 40mg (3), 60mg (7), 70mg (4), 80mg (6) QD and 20mg BID (2).Tumor types included breast (6), CRC (4), ovarian (3), H&amp;N (2), sarcoma (2), and NSCLC, sinus, gastric, gallbladder, pancreas, CUP tumor (1 each). Tumor genetic profiles were available for 20 pts. DLTs were G3 diarrhea, nausea, and vomiting, which occurred in 1 pt at 80mg QD and G3 Diarrhea, occurring in 1pt at 80mg QD. The most common adverse events related to study drug were diarrhea (60.9%), nausea (47.8%), vomiting (43.5%), fatigue (21.7%), decreased appetite (17.4%) and lipase increased (17.4%). Serious adverse events (SAEs) related to study drug were reported in 4pts: diarrhea (1 pt, 70mg QD; 1pt, 80mg QD), nausea and vomiting (1pt, 70mg QD), and diarrhea, nausea and vomiting (1 pt, 80mg QD). Stable disease has been observed in 7pts up to 24 weeks, in which 2/28 pts (7%) achieved tumor shrinkage. Conclusions: Based on the present data, KBP-5209 has been well tolerated with a safety profile similar to other pan-HER inhibitors. For QD dosing, maximum tolerated dose has been identified as 70mg QD. The BID dose escalation continues. Clinical trial information: NCT02442414.
Relative thrombocytosis following chemoradiation of patients with glioblastoma to predict survival.
Authors: Keeratikarn Boonyawan, Jie Yang, Lihong Long, Qianghu Wang, Ravesanker Ezhilarasan, Audia Alessandra, Kenneth R. Hess, Kristin Alfaro, John Frederick De Groot, Krishna Bhat, Erik P. Sulman
Journal: Journal of Clinical Oncology (2017)

e13527 Background: Thrombocytosis is associated with poor survival in several malignancies and is both triggered by and promoting of tumor growth. We hypothesized that an increase in circulating platelets following standard temozolamide (TMZ) CRT and/or adjuvant TMZ would predict for decreased survival in patients with glioblastoma (GBM). Methods: We reviewed data of 122 patients with newly diagnosed, pathological-proven GBM from 2007 to 2016 with documented complete blood counts before the start of CRT, after CRT, before adjuvant TMZ, and after a minimum 2 cycles of adjuvant TMZ. The association between changes in blood count levels and patient survival was analyzed by log-rank test. Multivariate analysis was performed using known prognostic co-variates, including MGMT methylation, patient age, and performance status (PS). Results: The mean change in platelets before and after CRT was -46 k/µl (range -387 to 179 k/µl) and before and after adjuvant TMZ was -25 k/µl (range -408 to 143 k/µl). As a reference, the mean change in lymphocytes was -5.7 k/µl (range -0.7 to 1.3 k/µl) and -0.0 k/µl (range -1.6 to 0.9 k/µl) for CRT and adjuvant TMZ, respectively. Patients were dichotomized based on the relative change in platelets and lymphocytes from baseline (≤30% increase, “low”, n = 101 vs &gt; 30% increase, “high”, n = 12). The median survival of low patients vs. high patients was 30 vs 13 months (p = 0.006). Potential confounders, such as infection or thrombosis, were not associated with the high group. However, no significant survival difference was observed between groups based on platelet changes during adjuvant TMZ. Similarly, changes in lymphocyte counts were not significantly prognostic. In multivariate analysis, extent of resection, MGMT status, PS and the increase in platelets after CRT were significantly associated with survival (HR for platelets 4.0, 95% CI 1.6-10.1). Conclusions: Increased platelet counts after CRT predict for poor survival in patients with GBM. The effect is platelet specific and does not reflect general bone marrow changes, as lymphocyte changes were not significantly prognostic. These results suggest a potential interaction between platelets and tumor aggressiveness.
A first-in-human first-in-class (FIC) trial of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in patients with advanced solid tumours
Authors: R. Plummer, S. Halford, P. Jones, S. Wedge, S. Hirschberg, G. Veal, G. Payne, M. Chenard-Poirier, H. Keun, U. Banerji
Journal: Annals of Oncology (2018)
Results of a phase Ib study of ARQ 092 in combination with carboplatin (C) plus paclitaxel (P), or with P in patients (pts) with solid tumors.
Authors: Nehal Lakhani, Anthony W. Tolcher, Drew W. Rasco, Amita Patnaik, Timothy J. O'Rourke, Brian E. Schwartz, Giovanni Abbadessa, Julia Kazakin, Ronald Savage, Yunxia Wang, Feng Chai, Kyriakos P. Papadopoulos
Journal: Journal of Clinical Oncology (2017)

2524 Background: ARQ 092 is an oral, potent AKT inhibitor with single agent antitumor activity. P or P+C is the standard therapy or the therapy of choice for pts with various solid tumors. ARQ 092 potentiated antitumor activity of P in in vivo xenograft models, providing the rationale for this study. Methods: This is an open-label, phase Ib study of ARQ 092+C+P (CP Arm) or ARQ 092+P (P Arm) in pts with advanced solid tumors to determine safety and tolerability of these 2 combinations. Blood samples are collected for PK. Results: Enrollment into CP Arm has been completed with 13 pts (15% male; median age 62 years, 4 ovarian, 9 others) being treated in 2 dose cohorts (see table and results below). Enrollment into P Arm is ongoing. Data from P Arm (80 mg/m2 weekly) will be presented during the meeting. In CP Arm, 3 DLTs were observed in 2 pts (both received ARQ 092 at 200 mg BID, 1 day/week) including grade (G) 4 neutrophil count decreased, G 4 thrombocytopenia and G 3 diarrhea. ARQ 092-related adverse events (AEs) in ≥10% pts included diarrhea 69%, fatigue 54%, hyperglycemia 31%, maculopapular rash 31%, nausea 23%, mucosal inflammation 23%, anemia 15%, platelet count decreased 15% and hypokalemia 15%. Paclitaxel- and/or carboplatin-related AEs in ≥10% pts included fatigue 77%, alopecia 62%, thrombocytopenia 39%, platelet count decreased 39%, nausea 31%, lymphocyte count decreased 31%, neutrophil count decreased 31%, white blood cell count decreased 31%, anemia 23%, mucosal inflammation 23%, hypomagnesaemia 23%, peripheral sensory neuropathy 23%, neutropenia 15%, vomiting 15% and hypokalemia 15%. Two ovarian pts previously treated with CP achieved complete response (mutant AKT) and partial response (AKT mutation unknown) respectively and 3 pts (Gastroesophageal, pancreatic, ovarian mixed mullerian) experienced stable diseases for &gt;12 weeks. PK data will be presented during the meeting. Conclusions: Encouraging anticancer activity was demonstrated in heavily pretreated ovarian cancer pts, but full dose CP was not tolerated by most patients. Clinical trial information: NCT02476955. [Table: see text]
Family and personal cancer history in young patients with pregnancy associated breast cancer.
Authors: Zorica Tomasevic, Zoran Tomasevic, Ivana Bozovic-Spasojevic, Kristina Serovic, Aleksandar Stojanovic, Zdravko Zdrale, Dobrica Neric, Zeljko Kovac
Journal: Journal of Clinical Oncology (2016)

e13098 Background: Breast changes during pregnancy/lactation might mask underlying BC, delaying diagnose even in patients with known positive family history (FH) for breast/ovarian cancer (BC/OC). Also, personal history (PH) for certain malignancies if treated with radiotherapy to the chest increase risk for BC but, during pregnancy this is sometimes ignored both by patients and physicians. However, data about FH/PH are not well explored in subgroup of patients with pregnancy associated BC (PABC) Therefore, we analyzed FH for BC/OC and PH in a subgroup of patients who developed PABC during or within 3 years of pregnancy. Methods: A cohort of 131 patients with invasive BC, median 33 years of age (range 22-40) has been prospectively identified from January 1st 2013 to December 31st 2015 at the Institute for Oncology and Radiology of Serbia. BC histology, molecular characteristics, tumor size, nodal status, initial stage, history of pregnancies, FH for BC/OC, and PH for malignancies, has been recorded. Results: PABC is diagnosed in 46 patients (35%); 20 (43.4%) were diagnosed from 6 weeks of pregnancy to 3 months after delivery; 5 (10.8%) within 3.1-12 months after delivery. Remaining 21 pts (45.6%) developed BC between 12.1-36 median 24 months after delivery. Median age was 33 years (24-40); 28 (61%) patients were diagnosed in stage 3-4. 12 patients (26%) reported FH + for female BC, none reported OC. Two patients had 2 family members with BC. Negative FH was reported by 25 pts (54 %), and 9 pts (19.5%) did not knew details of FH. PH for previous malignancies was reported in 3 patients (6.5%). All had Hodgkin lymphoma (HL) during adolescence, treated with chemotherapy/ radiotherapy, and all developed triple negative PABC 20, 20 and 36 months after delivery. Patients with FH/PH+ represented 54% of stage 3-4 PABC. Conclusions: Amongst young BC patients, 35% developed PABC, and more than 30% of them reported FH+ for BC (26%) or PH+ for HL (6.5%). It is unknown whether pregnancy might influence risk for BC in patients with FH/PH+ and more research is needed.