tbuckley/cabot-search huggingface dataset:
Overall survival with preoperative biliary drainage in patients with resectable pancreatic cancer.
Authors: Tobin Joel Crill Strom, Sarah E. Hoffe, Shivakumar Vignesh, Jason Klapman, Cynthia L. Harris, Jungsun Choi, Gregory M. Springett, Kenneth L. Meredith, Pamela Joy Hodul, Mokenge Peter Malafa, Ravi Shridhar
Journal: Journal of Clinical Oncology (2014)

314 Background: Resectable pancreatic cancer patients often present with obstructive jaundice necessitating the placement of biliary stents or percutaneouse drainage catheters. We sought to evaluate whether preoperative biliary drainage affects recurrence and survival. Methods: An IRB-approved study was conducted on our institutional tumor registry to identify pancreatic cancer patients who were treated with upfront surgery between 2000 and 2012. Patients were then stratified by preoperative use of endoscopically placed stents (ERCP), percutaneous catheters (PTC), or no biliary drainage (NBD). The primary endpoint was overall survival (OS). Survival curves were calculated using the Kaplan-Meier method and the log-rank test. Multivariate analysis (MVA) was performed with a Cox regression model. Results: We identified 202 patients for the study (21 PTC; 89 ERCP; 92 NBD). Key differences between the 3 groups were mean pathologic tumor size (p=0.005), pathologic T3/4 (p =0.01), and pathologic N1 (p=0.007) status, with more aggressive pathologic features in PTC patients. PTC patients had a non-significant increase in rate of hepatic recurrences compared with ERCP and NBD patients (47.4% vs. 26.6% vs. 28.7%, respectively; p=0.20). PTC patients also had worse median and 3 year survival (21 months and 16%) compared to ERCP (23.3 months and 39%) and NBD patients (29 months and 45%, p=0.02). MVA revealed that PTC was an independent predictor of worse overall survival (HR 2.3[95% CI 1.3-4.0], p=0.005), along with pathologic tumor size (HR 1.1[1.0-1.3], p=0.008), nodes positive (HR 1.1[1.1-1.2], p=0.001), and post-operative CA19-9 &gt;90 (HR 2.6[1.5-4.4], p=0.001). Conclusions: Patients with resectable pancreatic cancer who require a pre-operative PTC drain had a non-significant increase in hepatic recurrence rate and worse overall survival than patients who either had an ERCP stent placed or no biliary decompression prior to surgery. Given their worse prognosis, patients who require PTC placement might also benefit from neoadjuvant treatment with restaging prior to surgery.
Determina KRAS: A consolidated project.
Authors: Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

428 Background: The identification of KRAS mutation status as a predictive biomarker for the activity of anti-EGFR in mCRC patients, was the start of the personalize medicine. ASCO recognized it as a major advance in 2008 and it also gave a clinical opinion so every candidate for anti-EGFR therapy should be tested for KRAS mutations. NCCN guidelines recommends to do it at the first diagnose of metastatic disease. KRAS status testing was no widely available in Spain by 2008. The project Determina KRAS was developed in order to provide access to this test throughout the country to any mCRC patient. Methods: Five well known Spanish centres were trained and provided with equipment so they could analyze KRAS status in a five working day period. First centre was initiated in July 2008, being the last one in October 2008. A validated KRAS mutation kit (DxS Ltd, Manchester, UK) which identifies 7 different somatic mutations located in codons 12 and 13 using allele-specific real-time polymerase chain reaction was used. Results: 15.330 samples from mCRC patients have been analyzed since July 2008. 53,7% samples showed wild type KRAS status. G12D mutation was the most frequent mutation observed in general (35,1% of all mutation). G13D mutation was the most frequent of the codon 13 mutation, with a 20,2% of the global mutations. Conclusions: KRAS status testing allows to patients with mCRC receive a personalized medicine. KRAS status testing is essencial for treatment decision-making in mCRC and access to it must be guaranteed for any patient. The determination of biomarkers to choose the most effective treatment for each patient will be the future of oncology. These futures assessments must be available for all patients through national Networks, as the Determina KRAS project has made with KRAS testing.
Prognostic value of the circumferential resection margin after neoadjuvant treatment in esophageal cancer patients.
Authors: Jan-Binne Hulshoff, Zohra Faiz, Justin Kendrick Smit, Gursah Kats-Ugurlu, Johannes Burgerhof, John Theodorus Plukker
Journal: Journal of Clinical Oncology (2015)

147 Background: Involvement of the circumferential margin (CRM) is an important factor in esophageal cancer (EC) patients. CRM definitions are commonly based on the College of American Pathologists (CAP) at 0 mm and the Royal College of Pathologists (RCP) at &gt;1 mm. We evaluated which CRM definition is useful in current practice with neoadjuvant chemoradiotherapy (CRT) and whether the CRM cut-off value differs after CRT. Methods: We prospectively included 209 patients (104 with CRT) with locally advanced EC (stage II-III), who underwent radical transthoracic esophagectomy. Patients were followed for at least 2 years after surgery or until death. Patients with &lt;1 mm longitudinal resection margins were excluded. Cancer related death was scored as event and death of other causes as end of follow-up (median 27: IQR 14.0 - 42.8 months). CRMs were measured in tenths of millimetres by experienced pathologists. Pathologic proven tumor regrowth, unequivocal radiologic suspicion or obvious clinical manifestations were marked as recurrence. Prognostic factors with a P&lt;0.1 in univariate analyses were incorporated in multivariate Cox-regression analyses in which both CRM definitions were assessed separately. In an explorative analyses the CRM cut-off values in the surgery-only and CRT group for 2-year disease free survival (DFS) was assessed using CRM between 0-1.5 mm in the Cox-regression model. Results: Independent prognostic factors for 2-year DFS (P&lt;0.05) in the study group were: tumor length (&gt;5cm), &gt;0.2 L/N+ ratio, angioinvasion and CAP R0. In the surgery group; tumor length, &gt;4 N+, angioinvasion and CAP R0 were independent prognostic factors (P &lt;0.05). In the CRT group only pN stage (P&lt;0.01) was independent prognostic for 2-year DFS. The CRM cut-off value was significant at 0.2-0.3 mm for the surgery and CRT group, respectively. Conclusions: The CAP value was only independent prognostic for 2-year DFS in the surgery group. The CRM cut-off value was significant at 0.2 and 0.3 mm in the surgery and CRT group, respectively.
Risk of primary progressive disease with tyrosine kinase inhibitors sorafenib and sunitinib in patients with renal cell carcinoma: A meta-analysis.
Authors: X. Su, V. Ranpura, S. Wu
Journal: Journal of Clinical Oncology (2010)

4616 Background: Tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib are used extensively in the treatment of advanced renal cell carcinoma (RCC). Treatment failure due to drug resistance can occur as primary or secondary progressive disease. To better understand the drug resistance, we performed a systemic review and meta-analysis of published clinical studies to determine the risk of primary progressive disease (PPD) with sorafenib and sunitinib in RCC patients. Methods: We searched databases from Pubmed, Web of Science, and abstracts presented at the American Society of Clinical Oncology conferences up to August, 2009 to identify relevant studies. PPD was defined as progressive disease as best response by RECIST criteria. Eligible studies include case series and clinical trials in which RCC patients were treated with sorafenib or sunitinib as a single agent. Incidence, relative risk (RR), and 95% confidence intervals (CIs) were calculated using a random-effects or fixed-effects model. Results: A total of 7,588 patients from 30 studies were included for analysis. The overall incidence of PPD with TKIs was 22.4% (95% CI: 18.7-26.6%), with 22.6% and 22.4% for sorafenib and sunitinib, respectively. There was no significant difference in the risk of developing PPD with TKI between non-clear-cell and clear-cell RCC (RR 1.09, p=0.086). Notably, prior cytokine therapy increased the risk of PPD with sunitinib (RR, 1.18, 95% CI: 1.05-1.34; p=0.007), but not sorafenib (RR, 0.97, 95% CI, 0.78-1.19; p=0.75), in comparison with no prior treatment. Furthermore, prior treatment with sorafenib did not significantly increase the risk of PPD with subsequent sunitinib in comparison with no prior treatment (RR 1.33, 95% CI: 0.98-1.80; p=0.069); however, prior treatment with sunitinib significantly increased the risk of PPD with subsequent sorafenib (RR 3.53, 95% CI: 2.88-4.34; p<0.0001). Conclusions: Early treatment failure from PPD in advanced RCC patients may vary with prior cytokine or TKI therapies. Sorafenib and sunitinib may have different mechanisms in the development of drug resistance. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Onyx, Wyeth
Time course of skin toxicity (tox) secondary to erlotinib (E) therapy in patients (pts) with non-small cell lung cancer (NSCLC) enrolled in the SATURN study.
Authors: R. Perez-Soler, F. Cappuzzo, L. Leon, S. Wojtowicz-Praga
Journal: Journal of Clinical Oncology (2011)

7610 Background: The objectives of this analysis were to evaluate the incidence, severity, time course and duration of skin tox secondary to E as well as the effects of E dose modifications on this tox, in the context of the SATURN study, a large randomized placebo controlled trial of E vs. placebo in pts with NSCLC in the maintenance setting. Methods: Retrospective analysis of pts entered in the SATURN study. Skin tox was recorded on CRFs and graded according to NCI common tox criteria version 3.0. Management of the skin rash was at the discretion of the treating investigator. Results: 438 pts received E and 451 pts received placebo. The incidence of skin tox was 61% in pts treated with E and 9% in pts treated with placebo. There were no significant differences in the duration of skin tox between the two groups (p-value = 0.3). A total of 266 E treated pts experienced skin tox. Dose modifications secondary to E treatment occurred in 43 pts (16%) and were initiated around week 6 (min=1, max=53). Most skin tox events were reported in the first 2 weeks (70%). The incidence and intensity of skin tox increased by week 3, and peaked on week 5 (3%, 50%, 39%, and 8% for grades 0, 1, 2 and 3), and progressively decreased thereafter. The same trends were observed when pts that had dose reductions due to skin tox were excluded from the analysis (3%, 54%, 39%, and 4% for grades 0, 1, 2 and 3). The incidence of grade 3 tox on week 5 was lower in the pts that were not dose reduced compared with the whole population (4% vs. 8%) suggesting that only half the pts with grade 3 tox were dose modified before week 5. The incidence of treatment discontinuation was slightly lower in the pts with skin tox (approximately 85% vs. 90% at year-1) but the difference was not statistically significant. Conclusions: 1. Skin tox secondary to E presents within the first 2 weeks in the majority of pts, peaks on week 5, and decreases thereafter; 2. The full E dose could be given to the great majority of pts. Skin tox only led to dose adjustments in about 50% of pts with grade 3 tox; 3. The presence of skin tox slightly decreased the incidence of treatment discontinuation but the difference was not significant.
Has venous thromboembolism (VTE) prophylaxis made any difference for solid tumor inpatients at Princess Margaret Cancer Center (PM)?
Authors: Tian Qi Wang, Carmen Tan, Eshetu G. Atenafu, Jack Toshimine Seki
Journal: Journal of Clinical Oncology (2016)

98 Background: VTE represents a significant risk for morbidity and mortality in cancer patients. Hospitalized solid tumor patients at PM are especially at risk (15% of inpatients experienced a VTE event in 2004 when prophylaxis rate was 19%). Institution-wide VTE prophylaxis policy was implemented, and prophylaxis uptake reached nearly 97% in Sept 2012. We are interested in whether the prophylaxis policy made any impact in reducing VTE incidences over time. Our objective is to compare inpatient VTE frequency before and after the implementation of the VTE prophylaxis policy (IPP) in Sept 2012 at PM. Methods: This retrospective study evaluated VTE frequency before and after IPP for all inpatients admitted to the 17A/B solid tumor units during the fiscal years 2007 to 2015. Eligible patients were those who became symptomatic and diagnosed 48 hours post hospital admission, as identified through the Discharge Abstract Database (DAD). Prophylaxis recipients were those without active bleeding and were not receiving treatment anticoagulant for a previous VTE. Results: 66 inpatients were identified to have developed VTE (table). The majority of inpatients who developed VTE had brain, lung, colorectal, pancreatic, or ovarian cancer. 83.3% of patients had a PADUA risk score of 4 or greater. From April 2007 to Sept 2012, 1 patient developed VTE every 105.7 patient visits (48 patients developed VTE in 5075 patient visits). From Sept 2012 to March 2015, 1 patient developed VTE every 112.6 patient visits (18 patients developed VTE in 2026 patient visits). Odds ratio of 0.9388 (CI = 0.5448-1.6177) showed lower VTE risk for patients on prophylaxis during admission. Conclusions: There appeared to be a decreasing trend in the frequency of VTE post-IPP, for cancer inpatients within a limited population. [Table: see text]
Promoting healthy youth through a uterine cervical cancer screening program in Tucuman, Argentina.
Authors: C. E. Lorente, S. Holgado, A. d. C. Elias, M. Sanchez Segura, M. Aleman, G. Almada, L. Benegas, B. Bustos, V. Cano Busnelli, V. Contreras, M. P. Grondona, M. Jimenez, M. P. Manfredi, C. Ocampo, J. J. Zarba
Journal: Journal of Clinical Oncology (2011)

e12019 Background: The alarming misinformation among young people in Tucumán on: HPV, its prevention, its association with CC and with other cancers and the increased incidence of CC in young women, led a group of young University Students Volunteers (USV) -Biochemistry, Biotechnology, Medicine and Psychology- to develop tasks for Sex Education in High schools (HS) of Tucumán since 2008. The volunteer projects were “HPV-Pass the word not the disease
Freedom from recurrence after induction cisplatin/5-FU/RT versus carboplatin/paclitaxel/RT in patients with esophageal cancer.
Authors: Alan Adolph Thomay, Stacey Su, Adam J. Friedant, Karen J. Ruth, Igor A. Astsaturov, Barbara Burtness, Crystal Shereen Denlinger, Efrat Dotan, Michael J. Hall, Joshua E. Meyer, Prashant C. Shah, Steven J. Cohen, Walter J. Scott
Journal: Journal of Clinical Oncology (2014)

126 Background: The optimal neoadjuvant treatment regimen for esophageal cancer has yet to be defined. Methods: We analyzed a prospective database of esophageal cancer patients treated with cisplatin/5-FU/RT (A) or carboplatin/paclitaxel/RT (B) then esophagectomy. Endpoints were pathologic response (pCR), recurrence, and overall survival. Covariates (age, gender, clinical stage, Charlson comorbidity index (CCI), and ECOG PS) were adjusted via propensity score weighting from logistic regression. Differences in survival curves were compared using weighted Kaplan Meier methods and Wilcoxon tests. Landmark analysis compared differences in outcomes at least six months after surgery. Results: From January 2008 to June 2013, 71 patients received induction RT (50.4 Gy), with 38 and 33 patients in groups A and B, respectively. Patient demographics were similar (Table 1). Operative procedure, R0 resections, and operative complications did not differ (operative mortality 1/71, 1.4%; anastomotic leak rate 10% A vs. 9% B, p=1.0). Median follow-up was 18.2 and 9.1 months for groups A and B, respectively. There was no difference in overall survival (p=0.88) or total number of recurrences (11/38, 29% A vs. 10/33, 30% B). Landmark analysis revealed a difference in recurrence at least 6 months after surgery: time to recurrence was shorter in group B (median time to recurrence 31 mos A vs. 18 mos B, p=0.02). pCR was seen in 13/38 (34%) A and 9/33 (27%) B (p=0.53). In patients with pCR, there was a trend toward more recurrences in group B (2/13, 15% A v 4/9, 44% B, p=0.14). Conclusions: Six months after surgery patients receiving induction carboplatin/paclitaxel/RT had shorter time to recurrence compared to cisplatin/5-FU/RT. In those with pCR a trend towards increased distant recurrences was seen with carboplatin/paclitaxel/RT, which may have less systemic efficacy in esophageal cancer than cisplatin/5-FU/RT. This should be evaluated in larger series. [Table: see text]
International Recommendations for Electrocardiographic Interpretation in Athletes
Authors: Sanjay Sharma, Jonathan A. Drezner, Aaron Baggish, Michael Papadakis, Mathew G. Wilson, Jordan M. Prutkin, Andre La Gerche, Michael J. Ackerman, Mats Borjesson, Jack C. Salerno, Irfan M. Asif, David S. Owens, Eugene H. Chung, Michael S. Emery, Victor F. Froelicher, Hein Heidbuchel, Carmen Adamuz, Chad A. Asplund, Gordon Cohen, Kimberly G. Harmon, Joseph C. Marek, Silvana Molossi, Josef Niebauer, Hank F. Pelto, Marco V. Perez, Nathan R. Riding, Tess Saarel, Christian M. Schmied, David M. Shipon, Ricardo Stein, Victoria L. Vetter, Antonio Pelliccia, Domenico Corrado
Journal: Journal of the American College of Cardiology (2017)
Hypertension as a clinical marker of response to bevacizumab across malignancies.
Authors: J. Munoz, B. E. Sanchez, M. Sharifi, D. Kostoff, H. Y. Ali, A. S. Hanbali, P. Kuriakose, I. S. Wollner
Journal: Journal of Clinical Oncology (2011)

e16601 Background: Bevacizumab, an inhibitor of the vascular endothelial growth factor (VEGF), has been shown to improve progression-free survival (PFS) although current data does not support overall survival (OS) benefit. Studies have been designed in an attempt to find a marker for activity albeit ways to predict response to anti-VEGF therapy are currently lacking. Methods: Retrospective chart review of 454 patients exposed to bevacizumab since 2004 to 2009. The study comprised 157 patients with colon cancer, 127 with glioblastoma, 104 with lung cancer and 66 with breast cancer. Group A represented patients that while treated with bevacizumab developed hypertension or, if already hypertensive, required an increase on their antihypertensive regimen. Group B represented patients that while treated with bevacizumab did not develop hypertension or, if already hypertensive, did not require an increase on their antihypertensive regimen. Results: Median survival (Table 1) is significantly higher in group A (607 days) than group B (355 days), with a log-rank p-value of <0.0001. Median PFS (Table 2) is significantly higher in group A (197 days) than group B (117 days) with a log-rank p-value of <0.0001. Next, multivariate analyses were done for OS and PFS using Cox proportional hazards models. Age group, gender, line of treatment, and single agent versus combined use of bevacizumab were not significant predictors on univariate analyses thus only cancer type was entered into the multivariable model with group. The results for OS (Table 3) indicate that being in group B raises the risk of death by 53.3% when holding type of cancer constant. The results for PFS (Table 4) indicate that females have a 27.3% decreased risk of progression than males when holding group and type of malignancy constant. If a patient is in group A their risk of progression decreases by 32.6% when holding gender and type of malignancy constant. Conclusions: Bevacizumab has proven activity across malignancies nevertheless we have yet to determine which specific patients benefit from its use. Our study shows that hypertension is a clinical surrogate of response to bevacizumab and encourages continuation of anti-VEGF therapy while optimizing anti-hypertensive regimen.
The burden of metastatic melanoma (mM): Treatment patterns, healthcare use, and costs.
Authors: C. Reyes, S. DaCosta Byfield, S. Satram-Hoang, A. H. Teitelbaum
Journal: Journal of Clinical Oncology (2011)

8565 Background: Treatment (tx) of mM with currently available therapies is often of limited clinical benefit, with infrequent durable responses and relatively low survival. Few studies have examined health care utilization (HCU), costs and treatment patterns of the disease. Methods: A claims-based analysis was conducted using data from 1/2007 to 3/2010 from a national commercial health insurer. Patients (pts) included were ≥18 yrs, had ≥ 2 claims for metastatic disease (ICD-9-CM 196.xx-198.xx) ≥ 30 days apart, and ≥ 2 claims for melanoma (ICD-9-CM 172.xx) ≥ 30 days apart or ≥ 1 claim for cancer-related tx with a dx of melanoma. The index date was the first mM dx date; those with a 2nd primary cancer were excluded. Pts were continuously enrolled for 6 mo prior (baseline) and ≥ 3 mo after the index date (follow-up). Treatment patterns, total HCU, average per-patient per-month (PPPM) costs, best supportive care (BSC) - defined as hospice after the end of systemic therapy - and mortality were examined. Results: The study included 829 mM pts with a mean age of 58.8 yrs, mean baseline comorbidity index of 3.42 and most (65%) were male. Throughout the study period, 71% and 10% of pts had evidence of immunohistochemistry and molecular testing, respectively. Only 431 (52%) and 103 (12%) had evidence of starting 1st-line and 2nd-line tx respectively. Most (50%) were treated with single-agent temozolomide or interferon alfa. The rate of HCU (events/person-yr) increased 1.5-5 fold from baseline to follow-up (p<0.01); 0.28 vs. 1.40 for inpatient, 19.11 vs. 29.64 for office visits, 12.03 vs. 26.86 for outpatient visits and 0.96 vs. 1.45 for ER visits. Mean PPPM health care costs increased from $1,855 at baseline to $9,495 during follow-up (p-value <0.01). Among the entire study cohort, 173 (20.9%) had evidence of BSC and 289 (34.7%) died. Among those who died, mean survival time was 285 days. Conclusions: Resource utilization and cost increase considerably after development of metastases in pts with melanoma. The low proportion of patients with 1st- or 2nd-line tx suggest frequent enrollment in clinical trials as an early or intervening tx. More effective tx, like those targeting relevant biomarkers, are needed to improve outcomes and reduce the burden of mM.