tbuckley/cabot-search huggingface dataset:
Factors predicting clinical outcome of induction hypomethylating agents in older patients with acute myeloid leukemia.
Authors: Nischala Ammannagari, Monica Reddy Muppidi, Laurie Ann Ford, Elizabeth A. Griffiths, Evelena Ontiveros, James E. Thompson, Eunice S. Wang
Journal: Journal of Clinical Oncology (2016)

7037 Background: Hypomethylating agents (HMA) are increasingly being utilized for upfront therapy of acute myeloid leukemia (AML) in older adults. These individuals often have multiple comorbidities and/or lower performance status predicting for poor outcome following intensive induction chemotherapy. We asked whether these same clinical factors influenced the outcomes of HMA induction therapy in older adults. Methods: We reviewed 138 consecutive patients aged ≥ 60 years who received upfront HMA with either decitabine (20 mg/m2 for 5-10 days) or azacitidine (75 mg/m2 for 7 days) for newly diagnosed AML at our institute. ECOG PS, comorbidities, Charlson Comorbidity index (CCI), Hematopoietic Cell Transplant – Comorbidity Index (HCT-CI), and overall survival (OS) were assessed. Results: Median age was 75 (range 60-93) years. Two-thirds (95) were male. Median white blood cell count was 4.5 x 109/L (0-121). Median marrow blasts were 45% (10-98%). Half of patients (50%) had secondary AML. 87 (63%) had adverse cytogenetics, 13 (9%) had FLT-3 mutant and 14 (10%) had NPM-1 mutant AML. ECOG PS was assessed as 0 (20 pts, 14%), 1 (85 pts, 62%), 2 (29 pts, 21%) and 3 (4 pts, 3%). Comorbidities were measured as 0 (24 pts, 17%), 1 (51 pts, 37%), 2 (32 pts, 23%) or ≥ 3 (31 pts, 23%). CCI was 2-3 (20 pts, 14%), 4-5 (63 pts, 46%), 6-7 (42 pts, 31%), and ≥ 8 (13 pts, 9%). HCT-CI was 0-1 (40 pts, 29%), 2-5 (78 pts, 56%) and 6-12 (20 pts, 15%). The majority (115, 83%) of patients received decitabine induction. Twelve patients (9%) underwent stem cell transplant. Median OS of all patients was 7.47 months. Factors significantly associated with poorer outcome by log-rank analysis were: age ≥ 75 (p = 0.0001), marrow blasts < 50% vs ≥ 50% (p = 0.002), ECOG PS 2-3 (p = 0.04), CCI ≥ 6 (p = 0.0006), HCT-CI 0-1 vs 2-5 (p = 0.0129), HCT-CI 2-5 vs 6-12 (p = 0.0066). Choice of HMA, number of comorbidities, and de novo vs secondary AML did not predict outcomes. Conclusions: Advanced age ≥ 75 yrs, marrow blasts ≥ 50%, ECOG PS 2-3, and high comorbidity indices, as determined by CCI and HCT-CI, were associated with shorter overall survival following induction HMA in older AML patients. Future prospective studies to validate these findings are needed.
One year experience of <i>MET</i> gene exon 14 skipping analysis in lung cancer: Identification of 18 cases by NGS.
Authors: Hendrikus J Dubbink, Willemina Geurts-Giele, Isabelle Meijssen, Cor van der Leest, Robert Peric, Jan Von Der Thusen, Joachim Aerts, Winand N.M. Dinjens
Journal: Journal of Clinical Oncology (2017)

e20055 Background: Lung adenocarcinoma (LAC) is the most common histological type of non-small-cell lung cancer and is one of the malignancies with the most evolved personalized treatments based on molecular characteristics of the tumor. Mutations in EGFR, HER2 and BRAF, specific translocations of ALK, ROS1, RET and amplification of MET all have standard diagnostic importance and lead to specific treatment options for the individual LAC patients. Recently, in 2-4% of LAC MET gene mutations leading to skipping of exon 14 were found. These mutations were described to occur more frequently in tumors with sarcomatoid histology. LAC with MET exon 14 skipping mutations showed impressive, although temporary, responses to MET tyrosine kinase inhibitors (TKI) crizotinib, cabozantinib and capmatinib. We will present our experience with routine molecular diagnostic detection of the most common MET exon 14 skipping mutations. Methods: In January 2016 we included in our standard, DNA based, molecular diagnostics custom-made NGS analyses 4 amplicons for detection of MET skipping mutations. The analyses were performed on microdissected FFPE tissue sections or routine histology or cytology stained preparations. Nine different mutations were validated for their effect on splicing by RT-PCR on RNA isolated from the same tissue samples. Results: Between January 2016 and January 2017 676 routine molecular diagnostic analyses on LAC were performed. In 18 (2.7%) cases MET mutations were detected possibly resulting in exon 14 skipping. Nine out of 16 different mutations were tested by RT-PCR and all 9 were demonstrated to result in MET exon 14 skipping. Conclusions: MET exon 14 skipping mutations can reliably be detected in routine pathology tissue samples. These analyses can easily be included in routine molecular diagnostic NGS. When necessary, confirmation of the mutational effect on RNA splicing can be implemented as well. Routine identification of MET skipping mutations (2.7% of cases) adds substantially to the personalized targeted treatment strategies for LAC patients.
Clinical presentation, treatment and outcome of a cohort of pancreatic ductal adenocarcinoma (PDA) patients in Mexico.
Authors: Vanessa Rosas Camargo, Angela Rosales Sotomayor, Mónica Isabel Meneses Medina, Carlos Chan Nuñez, Armando Gamboa Domínguez, Miguel Ángel Ramírez Luna, Alejandro Noguez-Ramos, Luis Federico Uscanga Domínguez, Fidel David Huitzil Melendez
Journal: Journal of Clinical Oncology (2018)

e16260 Background: Diagnostic and treatment delay for PDA patients (pts) has been reported in Mexico with possible survival compromise. Methods: A retrospective review of medical records of all consecutive pts with histological diagnosis of PDA evaluated at our Institution from January 2004-December 2013. Clinical, pathological and laboratory variables at diagnosis were recorded. Overall survival (OS) was estimated using Kaplan-Meier method and survival distributions were compared using the Log-rank test. Statistical significance was determined at P < 0.05. Results: 400 pts with biopsy-proven PDA were evaluated. Median age was 62 y/o, 51% female gender, and 54% positive smoking history. Symptoms at presentation: 79% abdominal pain, 68% non-specific gastrointestinal symptoms, 68% weight loss, 56% jaundice. Median laboratory values were total bilirubin 1.7 mg/dL (0.1-42), albumin 3.3 g/dL (1.2-5.2), CA 19.9 360.9 U/mL (0.6-41320), 29% NL ratio ³ 5. The main location was in the head (69%). Resectability status was: 27% localized resectable (LR), 3% borderline resectable (BR), 19% locally advanced unresectable (LA), 51% advanced disease (AD). Resectability rate was 61% for LR+BR (68 Whipple procedure). pT3 80%, N+ 54%, R1 39%. Specific morbidity: 15 hemorrhage, 9 delayed gastric emptying, 7 pancreatic fistula. Postoperative mortality was 13.5%. Adjuvant chemotherapy (CTX) could not be delivered to 40% of pts. Ultimately 232 pts had metastatic disease at diagnosis: 70% liver, 52% peritoneum, 38% lung. Palliative CTX was administered to 28% of pts. Median OS was 2.4 months (m): 7.1 m for LR, 4.9 m for BR, 4.4 m for LA and 0.8 m for AD (P= .000). Conclusions: Prognosis is poor mainly due to advanced disease at presentation and limited treatment access. Rates of adjuvant and palliative CTX are low. Those who receive appropriate and timely therapy have similar results to international standards. Efforts should be focused on early referral and improve access to multimodal therapy. Patients optimally treated (%) and survival. % Median OS (95% CI) Resected (N 74) Resection+adjuvant CTX 57 26 (10.9-41.1) LA (N 94) CTX 25 12.3 (10.4-14.2) CTX+chemoradiation 9 14.2 (8.7-19.6) AD (N 232) Palliative CTX 28 5 (4.2-5.8)
Clinical features of extremity or trunk sarcomas in patients aged 80 or older.
Authors: Jungo Imanishi, Lester Chan, Matthew Broadhead, Sam Ngan, John Slavin, Grant Pang, Peter Choong
Journal: Journal of Clinical Oncology (2016)

e22546 Background: Because of the dramatic increase in life expectancy in recent decades, the treatment of malignant neoplasm in elderly people has become the focus of attention. However, little is known about soft-tissue sarcomas in the elderly population. Methods: Subjects were retrieved from the institutional database. Inclusion criteria were (1) no metastasis at first presentation, (2) extremity or trunk wall sarcomas, (3) surgery at our institution in 1996–2012, and (4) ≥ 2 years of follow-up for non-event patients. Patients referred after unplanned excision followed by re-excision at our institution were included, but intermediate malignancy tumors, such as well-differentiated liposarcoma and solitary fibrous tumor, were not included. Patient information including age, gender, pathological diagnosis, FNCLCC grade, size, depth, surgical margin status, was collected. Patient characteristics and clinical outcomes, local-recurrence-free survival (LRFS), disease-specific survival (DSS), and overall survival (OS), were compared between patients aged < 80 and ≥ 80. A P-value of < 0.05 was regarded as statistically significant. Results: A total of 369 cases were included in this study. Thirty-six patients (10%) were aged ≥ 80. The older group ( ≥ 80) was significantly higher FNCLCC grade and had a significantly lower adjuvant chemotherapy administration rate. The margin status was comparable between the two groups (Table). LRFS, DSS, and OS were compared among grade 2 or 3 (G2/3) sarcomas. 5-year LRFS, DSS and OS for sarcomas aged ≥ 80 vs. < 80 were 72% vs. 90% (P = 0.0048), 57% vs. 79% (P = 0.0079) and 45% vs. 75% (P < 0.0001), respectively. In the cohort of G2/3 (n = 323), Cox analysis with backward elimination method revealed age ≥ 80 as an independent risk factor for poorer LRFS and DSS, with hazard ratio of 2.93 (95% CI: 1.34–6.40) and 2.09 (1.15–3.81), respectively. Conclusions: Despite similar treatment strategy except lower chemotherapy administration, prognosis of G2/3 sarcomas in patients aged ≥ 80 was significantly worse. Characteristic ≥ 80 < 80 Pa n = 36 n = 333 ≤ 5 cm 28% 43% 0.07 Superficial 25% 29% 0.65 G1 0% 14% 0.001* G2 31% 32% G3 69% 54% Inadequate margin 8% 5% 0.50 Adjuvant radiotherapy 89% 87% 0.75 Adjuvant chemotherapy 0% 6% 0.045*
Make it REAL: four simple points to increase clinical relevance in sport and exercise medicine research
Authors: Thomas Bandholm, Marius Henriksen, Shaun Treweek, Kristian Thorborg
Journal: British Journal of Sports Medicine (2018)

Clinical sport and exercise medicine (SEM) research is a branch of ‘clinical research’, a term meant to cover all types of investigations that address questions on the prevention, treatment, diagnosis/screening or prognosis of disease or enhancement and maintenance of health.1 As such, clinical SEM research should be useful and inform evidence-based decision making. While this may seem intuitively correct, careful considerations about whether our research is relevant for others than ourselves is an important exercise to facilitate ‘real world’ implementation. Because the current research reward system values research quantity more than quality (publish or perish), it is understandable why we sometimes forget to slow down2 and consider relevance for others than ourselves.

Recently, different initiatives concerning patient-relevant outcomes3 and partnering with patients4 have increased attention towards addressing the relevance of clinical research from an end-user perspective. This focus is also increasing in clinical SEM where involvement of end-users is part of tools to bridge the science–practice gap.5 In this editorial, we focus on a few simple, yet important points, to obtain stakeholder involvement …
TCT-500 Prognostic Implications of Reduced Pre-procedural TIMI Flow in Patients with Non–ST-Segment Elevation Acute Coronary Syndromes Undergoing PCI
Authors: Mordechai Golomb, Rafal Wolny, Yangbo Liu, Patrick Serruys, Clemens von Birgelen, Pieter Smits, Bjorn Redfors, Mahesh Madhavan, Ori Ben-Yehuda, Roxana Mehran, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Unexpected lymphatic drainage pathways of cervical cancer: Insights of the sentinel lymph node biopsy.
Authors: Vincent Balaya, Patrice Mathevet, Laurent Magaud, Denis Querleu, Eric Leblanc, Philippe Morice, Emile Darai, Anne-Sophie Bats, Cyrille Huchon, Fabrice Lecuru
Journal: Journal of Clinical Oncology (2018)

5532 Background: Sentinel lymph nodes (SLNs) can be observed in various territories. An intraoperative surgical strategy is needed to find all relevant SLNs and limit the risk of missed SLN. The aim of this study was to define an anatomically based surgical algorithm to identify sentinel lymph nodes (SLNs). Methods: We analyzed the data of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) in women undergoing surgery for early-stage cervical cancer. SLN detection was realized with a combined labeling technique (Patent blue and radioactive tracer). Results: A total of 377 patients with 1186 intraoperative detected SLNs were analyzed. 201 SLNs were only blue, 291 SLNs were only hot and 685 SLNs were blue and hot. The SLNs were located in the ilio-obturator or extern iliac area in 82.1 % of cases (974/1186) corresponding to the upper parametrial pathway (UPP) and 362 patients (96%) had at least one SLN in these areas. The SLNs were located in other unexpected areas in 17.9% of cases (212/1186). 130 patients (34.5%) had at least one SLN in an unexpected area and 14 (3.7%) patients had SLNs only in in an unexpected area. 176 SLNs (14.8%) were located in the lower parametrial pathway (LPP) with 45 in the parametrium (3.8%), 109 in the common iliac area (9.2%), 22 in the promontory area (1.9%)) whereas 36 SLNs (3%) were located in the infundibulo-pelvic pathway (IPP) with 26 in the paraaortic area (1.9%), and 13 in other areas (1.1%). The lymphatic drainage was exclusively through the UPP in 57.2% of cases (679/1186), through the UPP and another pathway in 40.8% of cases (484/1186) and exclusively through the LPP or the IPP in 1.9% of cases (23/1186). Conclusions: The SLNs search should begin in the ilio-obturator and external iliac area. Other territories should be explored in the absence of SLNs in this first level or as a complement. Pelvic dissection should be done only in case of absence of SLN in all territories.
A Retrospective Case Control Study to Identify Differences in Risk Factors for the Development of Renal Cell Carcinoma in Patients Treated at a Safety Net Hospital Compared to Patients Treated at a Private Hospital.
Authors: Sung-Hee Choi, Joseph Allen Moore, Xin Luo, Yang Xie, Yull Edwin Arriaga
Journal: Journal of Clinical Oncology (2016)

e16122 Background: Renal cell carcinoma presentation, treatment, and outcomes vary widely according to socioeconomic factors and other patient characteristics. Our preliminary clinical observation suggests that patients at a safety net hospital present with renal cell carcinoma at a younger age, compared to patients at a private hospital. We therefore studied the differences in clinical presentation, risk factors and survival between these two distinct patient populations. Methods: We performed a retrospective analysis of consecutive patients diagnosed with renal cell carcinoma from 2000 to 2013 at a safety net and a private hospital affiliated with the University of Texas Southwestern Medical Center. Demographic, clinical and socioeconomic data were obtained from hospital tumor registries and individual patient records. The association between variables was assessed using univariate analysis, multivariate analysis and Kaplan-Meier survival analysis. Results: A total of 2487 patients met criteria for analysis. The median age at presentation was 55 and 60 years for the safety net and private hospital, respectively (p = 5.69 x10-16). In multivariate analyses, patient characteristics at the safety net hospital that were significantly associated with age of presentation included: race, ethnicity (Hispanic origin), stage at presentation, tumor grade, Body mass index (BMI), tobacco use and insurance type. Among patients age 35-54, age of presentation was significantly associated with race, ethnicity (Hispanic origin), BMI and insurance type. Overall survival was not significantly different between patients treated at two hospitals (p = .24). Conclusions: Patients with renal cell carcinoma at a safety net hospital presented at a younger age at the time of diagnosis compared to patients at a private hospital. Multiple variables, including BMI, race and ethnicity (Hispanic origin) were associated with age at the time of presentation. In this study, difference in patient characteristics were not associated with clinical outcomes, specifically overall survival.
A phase 3, randomized, open-label study of epacadostat plus pembrolizumab, pembrolizumab monotherapy, and the EXTREME regimen as first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M SCCHN): ECHO-304/KEYNOTE-669.
Authors: Ezra E.W. Cohen, Danny Rischin, David G. Pfister, Jan Baptist Vermorken, Yufan Zhao, Hema Gowda, Joy Yang Ge, Fan Jin, Kevin J. Harrington
Journal: Journal of Clinical Oncology (2018)

TPS6090 Background: Although the EXTREME regimen is a Category 1 evidence-supported combination recommended by NCCN guidelines as first-line (1L) treatment for patients with R/M SCCHN, it is associated with limited survival benefit and burdensome toxicities. There remains a high unmet need for more effective and well tolerated treatment strategies. Both the programmed cell death 1 (PD-1) receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme have been identified as key mechanisms that suppress T-cell–mediated antitumor immunity and induce tumor escape. Pembrolizumab (P) is a potent, highly selective humanized monoclonal antibody that directly blocks the interaction of PD-1 and its ligands. Epacadostat (E) is a potent, highly selective oral inhibitor of IDO1. Preliminary phase 1/2 data from the ECHO-202/KEYNOTE-037 study showed encouraging efficacy results and a tolerable safety profile with E + P in SCCHN. This randomized, open-label, phase 3 global study (NCT03358472) evaluates the efficacy and safety of E + P, P, and EXTREME as 1L treatment in patients with R/M SCCHN. Methods: Key eligibility criteria: histologically or cytologically confirmed R/M SCCHN considered incurable by local therapies, ECOG PS ≤1, no prior systemic therapy for R/M disease, and no prior IDO1 inhibitors or immune checkpoint therapies. Approximately 625 patients will be randomized 2:1:2 to E 100 mg BID + P 200 mg Q3W, P 200 mg Q3W, or EXTREME (cetuximab 400 mg/m2 Cycle 1 Day 1, then 250 mg/m2 QW + cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/day continuously over Days 1–4 Q3W). Stratification includes ECOG PS, p16 status, and prior definitive systemic treatment for locally advanced disease. Patients receive ≤35 cycles of E + P or P, or ≤6 cycles of EXTREME followed by cetuximab maintenance; and are treated until disease progression, intolerable toxicity, or investigator/patient decision to withdraw. Primary endpoints are OS and PFS (per RECIST v1.1 assessed by central radiologist review). Secondary endpoints include ORR, safety and tolerability, and patient-reported outcomes. Clinical trial information: NCT03358472.
Utility of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in hematopoietic stem cell transplantation (HSCT).
Authors: Patricia B. Mumby, Todd Doyle, William Adams, Elliott B. Hicks, Sarah Thilges, Hanh P. Mai, Scott E. Smith, Tulio Rodriguez, Aileen Go, David Marinier, Patrick J. Stiff
Journal: Journal of Clinical Oncology (2017)

10046 Background: The SIPAT is used to assess psychosocial risk in solid organ transplants but data in HSCT is lacking. We examined if pre-HSCT SIPAT scores predict mortality, morbidity, length of stay (LOS) and number of hospitalizations over a 1 year period. Methods: 89 adult HSCT (59% autologous, 38% allogeneic) pts from an academic medical center underwent the SIPAT pre-HSCT. Additional data were obtained on Day 0, and 3-, 6-, and 12-months. Univariable Cox proportional hazards models assessed the instantaneous risk of mortality at any given time after Day 0 as a function of baseline pt characteristics and the SIPAT score. Results: TheSIPAT categorized 28%, 66% and 5.7% respectively of the pts as excellent (E), good (G), and high risk (HR) candidates. One year post HSCT, 76% of E, 72% of G, and 40% of HR candidates were alive. Higher SIPAT scores were a significant predictor of mortality. Compared to E candidates, the HR candidates were 5.94 (95% CI: 1.31-26.81) times more likely to die any time after Day 0 – even after controlling for pts’ comorbidity index ( p = .02). Similarly, compared to G candidates, HR pts were 4.81 (95% CI: 1.33-17.47) times more likely to die even after controlling for pts’ comorbidity index ( p = .01). There was no difference between the G and E candidates on univariable ( p = .75) or multivariable analysis controlling for comorbidity index score ( p = .72). For every 1 point increase in pts’ adherence score, the risk of death was expected to decline by approximately 14% ( HR = 0.86, 95% CI: 0.78 – 0.96; p = .01). SIPAT items that predicted mortality were depression ( p = .02), deceptive behavior ( p &lt; .001) and moderate alcohol abuse ( p &lt; .001). In linear regression analysis, higher SIPAT score was associated with longer LOS ( p = .04) but not infection ( p = .23), GVHD ( p = .40), or number of hospitalizations ( p = .73). Because there were only 18 mortality events, multivariable analyses were limited. Future research will examine the effect of SIPAT on time to death controlling for other pt comorbidities. Conclusions: We found the SIPAT was able to predict mortality and LOS in HSCT pts. This finding if validated in a multi-center manner could be an important tool for HSCT pt selection.