tbuckley/cabot-search huggingface dataset:
Neoadjuvant therapy for adenocarcinomas of the duodenum and ampulla of Vater.
Authors: G. Manoukian, A. Lal, S. Wen, Z. Jiang, R. T. Shroff, R. A. Wolff, M. J. Overman
Journal: Journal of Clinical Oncology (2011)

279 Background: Adenocarcinomas of the ampulla of Vater and duodenum are both rare periampullary tumors with limited data regarding the use of neoadjuvant therapy. We sought to better define the role of neoadjuvant therapy as compared to adjuvant therapy in patients with high-risk disease. Methods: Retrospective review of the M. D. Anderson Cancer Center (MDACC) tumor registry from 5/1990 to 1/2009 identified 66 cases of ampullary (26 neoadjuvant, 40 adjuvant) and 41 cases of duodenal adenocarcinoma (18 neoadjuvant, 23 adjuvant). Only patients who received adjuvant or neoadjuvant therapy and underwent surgical resection at MDACC where included. High-risk factors were defined as T3 or T4, poor differentiation, or lymph node involvement. Relapse-free survival (RFS) and overall survival (OS) were calculated from the start of surgical resection. Results: Median age was 61 yrs (range 30-82) and 39% were female. Neoadjuvant (n=44) and adjuvant therapy (n=63) consisted of 5-FU chemoradiation in 93% and 65%, systemic 5-FU based chemotherapy only in 5% and 24%, and gemcitabine or irinotecan based therapy in 2% and 11%, respectively. Pathological high-risk factors were seen in 77% and 95% of neoadjuvant and adjuvant patients, respectively. Indications for neoadjuvant therapy were high risk disease (70%), poor surgical candidate (16%), and concern for possible metastatic disease (14%). In the neoadjuvant group T and N downstaging were observed in 25% and 32% of patients, respectively; 3 patients (7%) had a pathological complete response. Neoadjuvant as compared to adjuvant therapy had similar 5-year OS (66% vs. 59%, p =0.8) and 5-year RFS (54% vs. 59%, p=0.4). Variables significant (p &lt;0.05) in the multivariate analysis for OS were age &gt;60 yrs, lymph node involvement, and margin positivity; and for RFS were lymph node involvement and margin positivity. Neither tumor type (duodenal vs. ampullary; OS HR: 1.6, p =0.2; RFS HR: 0.9, p=0.8) nor treatment type (neoadjuvant vs. adjuvant; OS HR: 1.2, p =0.6; RFS HR: 1.1, p=0.7) were significant for OS or RFS in the multivariate model. Conclusions: Neoadjuvant therapy appears to be a viable approach for high-risk duodenal and ampullary adenocarcinomas. Further investigation of this treatment approach is needed. [Table: see text]
Persistence of Nondysplastic Barrett’s Esophagus Is Not Protective Against Progression to Adenocarcinoma
Authors: Rajesh Krishnamoorthi, Guilherme Piovezani Ramos, Nicholas Crews, Michele Johnson, Ross Dierkhising, Qian Shi, Brenda Ginos, Kenneth Wang, David Katzka, Navtej Buttar, Prasad G. Iyer
Journal: Clinical Gastroenterology and Hepatology (2017)
Radiotherapy, including sentinel lymph node, to superficial cancer of esophagus.
Authors: T. Kaburagi, H. Takeuchi, T. Oyama, R. Nakamura, T. Takahashi, N. Wada, Y. Saikawa, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

126 Background: It is known that esophageal cancer frequently causes lymph node metastasis. Even if relatively early stage of esophageal cancer, reaching muscularis mucosae (T1a-MM: Japanese Classification of Esophageal Cancer) causes subclinical node metastasis to about 10%. So when radiation therapy (RT) is administered to these patients, field of irradiation should include the areas where subclinical node metastasis may exist. But the wider field of irradiation is, the more likely adeverse event is to occur. In this study, we examined utility of RT based on sentinel lymph node (SLN) theory. Methods: Before irradiation, Tc-99m tin colloid solution was endoscopically injected to the submucosal layer around the primary tumor and lymphoscintigraphy was examined to detect SLNs. And the irradiation field was planned as SLN regions were included. Patients with esophageal squamous cell carcinomas (ESCC) that reach cT1a-MM or cT1b and patients with ESCC who had underwent endoscopic resection and pathologically diagnosed pT1a-MM or pT1b were eligible if they had clinically no lymph node metastasis, no distant metastasis and no advanced cancer in other site. Between April 2001 and December 2009, 17 of these patients were received RT based on SLN theory. We retrospectively examined them. Results: Characteristics of the 17 pts were: median age; 67 (58-82), male/female; 15/2, T1a-MM/T1b-SM1/T1b-SM2; 4/2/11, definitive RT/adjuvant RT; 10/7, RT alone/concurrent chemoradiotherapy; 1/16. Average dose of irradiation was 57.0 ± 6.4Gy. Median follow-up is 81.4 months (7.9-127.2). Ten pts with definitive RT gained complete remission. Two minor local relapses of the primary tumors were observed. They underwent salvage endoscopic resection and survive without other relapse. There was no treatment related death. Grade 3 or 4 late toxicity was not observed. No significant financial relationships to disclose.
Health preference instruments in a breast cancer population: Is there a ceiling effect when compared to the quality-of-life instruments?
Authors: P. K. Isogai, N. Mittmann, L. J. Bordeleau
Journal: Journal of Clinical Oncology (2008)

6597 Background: Determination of health preference is a common outcome measure used in economic evaluations and represents the societal valuation of the patient's health state. It can be measured with generic multi-attribute instruments. Multi-attribute health preference (HP) instruments have similar domains to oncology quality of life (QOL) instruments. It is possible that HP instruments may over or under estimate a patient's QOL. Methods: Consecutive breast cancer patients irrespective of stage and treatment attending an outpatient clinic were approached to enrol in a work productivity and QOL study. The Functional Assessment of Cancer Therapy- General (FACT-G) / -Breast (FACT-B), and the EQ-5D were used to assess QOL and HP, respectively. Total scores are 108 (FACT-G) and 148 (FACT-B). EQ-5D is a generic, multi-attribute instrument measuring health preference from 0 to 1 for 243 possible health states. The analysis was carried out post-hoc to investigate the ceiling effect with the EQ-5D and FACT. Results: A total of 151 patients with breast cancer participated in the study. Mean±SD age was 55.2±12.5 years and time since diagnosis ranged from 0.1 to 25.0 years. Mean±SD FACT-G and FACT-B scores were 79.3±16.6 and 105.2±21.6, respectively. A perfect score was observed in only one patient for the FACT-G, none for the FACT-B, and in 35 (23.2%) patients for the EQ-5D. Four EQ-5D health states accounted for half the sample, with perfect health being the most common. Mean±SD utility score was 0.80±0.16. A correlation test between the EQ-5D and both FACT scores demonstrated convergent validity (p<0.01). Conclusions: Ceiling effect was observed with the EQ-5D which has fewer questions and a smaller scale compared to the FACT. This may indicate that the EQ-5D is not as sensitive in a general breast cancer population. However, the mean utility score was comparable to other studies in women with breast cancer. Future studies should investigate the relationship between long term QOL and HP in a larger cohort of women with breast cancer taking into account disease stage and treatment strategy. No significant financial relationships to disclose.
Phase II study of neoadjuvant chemotherapy with docetaxel, capecitabine, cisplatin and bevacizumab for initially unresectable gastric cancer with invasion of adjacent organs or paraaortic lymph node metastasis.
Authors: Jwa Hoon Kim, Sook Ryun Park, Min-Hee Ryu, Baek-Yeol Ryoo, Kyu-Pyo Kim, Beom Su Kim, Moon-Won Yoo, Jeong Hwan Yook, Byung Sik Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2015)

e15060 Background: Previously, we showed neoadjuvant chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) provides a reasonable chance of curative surgery in initially unresectable gastric cancer (GC) with invasion to adjacent organs or paraaortic lymph node (PAN) metastasis (Ann Surg Oncol 2010;17:1024-32). The aim of this study is to evaluate the efficacy and safety of more intensified neoadjuvant DXP+ bevacizumab (BEV) in these patients (pts). Methods: Eligibility criteria included ≥ 18 years, ECOG PS 0-2, and unresectable GC with invasion to adjacent organs or PAN metastasis of > 1 cm in short axis on CT with uptake on 18F-FDG-PET. Pts received 6 cycles of neoadjuvant chemotherapy (docetaxel 60 mg/m2 iv on D1, capecitabine 937.5 mg/m2 twice daily on D1-14, cisplatin 60 mg/m2iv on D1, and BEV 7.5mg/kg iv on D1 every 3 weeks), followed by D2 surgery. The primary endpoint was the R0 resection rate. Results: Between July 2010 and December 2014, 31 pts were enrolled. Clinical characteristics were as follows: median age = 55 years (range, 33-70); PS 0/1 = 2/29; M/F = 26/5; and clinical stage IIIB/IIIC/IV = 7/7/17. Twenty-seven pts (87.1%) completed 6 cycles of chemotherapy and four discontinued treatment due to gastric perforation (n = 2), death from sepsis (n = 1), and tooth infection (n = 1). The most common grade ≥ 3 adverse events were neutropenia (71%), febrile neutropenia/infection with neutropenia (22.6%/3.2%), leukopenia (32.3%), stomatitis (16.1%), and anorexia (9.7%). The disease control rate was 100% and the clinical response rate was 64.3% (95% CI, 46.6-82.0%) in pts with measurable lesions. The R0 resection rate was 67.7% with 71.4% (10/14) in pts with unresectable locally advanced disease and 64.7% (11/17) in pts with PAN metastasis. 4 pts (12.9%) had a pCR. With a median follow-up of 29.5 months (range, 10.5-44.2), median PFS was 23.3 months (95% CI, 5.6-41.1) and median OS was 38.6 months (95% CI, 13.3-63.9). Conclusions: Neoadjuvant DXP + BEV was active with a promising R0 resection rate, pCR rate, and a manageable toxicity profile in pts with unresectable locally advanced or PAN metastatic GC. Clinical trial information: NCT01471470.
Long-term health care resource utilization in men with localized prostate cancer treated with radical prostatectomy: Data from CaPSURE
Authors: K. L. Greene, E. P. Elkin, L. Wilson, N. Sadetsky, J. M. Broering, J. Duchane, D. M. Latini, P. R. Carroll
Journal: Journal of Clinical Oncology (2005)

6078 Background: We analyzed the pattern of prostate cancer related and unrelated resource use (RU) after radical prostatectomy (RP) in a long-term cohort of men with prostate cancer (CaP). Methods: From the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a national disease registry of men with prostate cancer, we identified 1,865 men treated with RP for clinically localized disease between 1999–2002. RU questionnaires were completed at the time of RP, representing all RU for 6 months perioperatively, and at 6 month intervals thereafter. We assessed RU by 6 month time periods for office visits, hospitalizations, emergency room visits, outpatient procedures, medications, diagnostic tests, and medical supplies. Data from 1,427 patients who completed at least one questionnaire in the 24 months following RP were analyzed. RU was defined as related or unrelated to CaP. The percent and mean of each type of RU was determined at RP to serve as a baseline and at 6, 12, 18, and 24 months after RP. Data collected at each time point represents RU in the preceding 6 months. Results: Most patients were Caucasian, age 60–69, with 1–2 comorbidities. 53% were diagnosed with low risk prostate cancer (PSA <10, Gleason sum <7, T-stage 1–2a). Generally, we found overall RU related to CaP was highest at RP but decreased rapidly by 6 months when CaP related RU became stable. Conversely, RU unrelated to CaP showed a stable pattern at all time points. For example, at the RP six month time period, mean CaP related office visits was 4.0 vs. 0.9 at 24 months. In contrast, office visits unrelated to CaP remained constant (mean 3.9 at RP and 4.1 at 24 months.) CaP related hospitalizations, ER visits and outpatient procedures were uncommon. Medication use was consistent over time: a mean of 0.5 CaP related vs. 2.6 unrelated medications at RP compared to 0.5 and 3.0 at 24 months, respectively. Diagnostic testing related to CaP decreased from 54% at RP to 7% at 24 months. Conclusions: Overall prostate cancer disease burden after RP is high but short term. Unlike unrelated RU, prostate cancer related RU rapidly decreases by 6 months postoperatively, although it continues up to 24 months at a much lower level. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration TAP Imetrikus, Merck AstraZeneca, Pfizer TAP
Novel, Potent and Selective JAK2 Inhibitors.
Authors: Thomas Radimerski, Fabienne Baffert, Catherine H. Regnier, Alain De Pover, Carole Pissot, Marc Gerspacher, Josef Brueggen, Gisele Tavares, Francesca Blasco, David Ledieu, Lynda Nolan, Stephan Ruetz, Patrick Chene, Dirk Erdmann, Peter Drueckes, Pascal Furet, Marc Lang, Joerg Trappe, Eric Vangrevelinghe, Markus Wartmann, Francesco Hofmann
Journal: Blood (2009)
Advance-care planning quality improvement plan: A Cancer Care Ontario toolkit to support primary care teams to implement advance care plans in practice.
Authors: Jeff Myers, Suzanne Strasberg, Kathi Carroll, Zabin Dhanji, Ingrid Harle, Sara Urowitz, Tara Walton, Victoria Zwicker
Journal: Journal of Clinical Oncology (2014)

76 Background: In Ontario, the Ministry of Health and Long Term Care’s (MOHLTC) uses Quality Improvement Plans (QIPs) to drive system improvement aimed at providing high value, high quality care for all. To support the introduction of QIPs into the primary care sector, Cancer Care Ontario has developed an Advance Care Planning (ACP) toolkit for practices that include ACP as part of their annual QIP. ACP is an ongoing and dynamic process that involves a capable individual reflecting on their current values and beliefs for their health care, communicating their personal wishes for future health care and identifying an individual who will make decisions on their behalf in the event that they are unable to provide informed consent. The process is iterative and wishes may change over time with changes in health status. Methods: The ACP QIP was developed based on the Plan, Do, Study, Act cycle of continuous quality improvement. The ACP QIP provides primary care practices with detailed instructions on how to implement, monitor and report on an ACP Quality Improvement initiative. Importantly, the ACP QIP provides guidance and practical tools for developing objectives, establishing targets, and identifying measures and baselines for performance. CCO is actively promoting the ACP QIP in an effort to encourage uptake and broad adoption across Ontario. Results: There is now evidence that with ACP there is a greater likelihood EOL wishes will be both known and followed resulting in improved EOL care. ACP is also associated with decreased distress among the family members. Conclusions: Creating an ACP QIP supports primary care’s focus on advancing quality patient care. Importantly, implementing the ACP QIP into primary care practices has the potential to improve EOL care and secondarily reduce health care costs ultimately working towards achieving the triple aim of “better care, better health, and lower costs”.
Predictors of Transformation to Myelodysplasia/Acute Myelogenous Leukemia (MDS/AML) in Severe Congenital Neutropenia (SCN).
Authors: Laurence A. Boxer, Audrey Anna Bolyard, Peter E. Newburger, Mary Ann Bonilla, George Kannourakis, Yigal Dror, Daniel C. Link, Blanche P. Alter, Philip S. Rosenberg, David C. Dale
Journal: Blood (2007)
Association and prognostic impact of peripheral blood counts with tumor programmed death ligand one expression.
Authors: Daniel Lewis, Richard Wayne Joseph, Daniel Serie, Jeanette Eckel-Passow, Thai Huu Ho, John C. Cheville, Eugene D. Kwon, Robert Houston Thompson, Bradley C. Leibovich, Alexander S. Parker
Journal: Journal of Clinical Oncology (2015)

447 Background: Components of the peripheral blood counts (PBC) are associated with poor prognosis in patients diagnosed with non-metastatic clear cell renal cell carcinoma (ccRCC). Related to this, higher tumor expression of programmed death ligand one (PDL1) is also associated with poor ccRCC prognosis. Herein, we utilize a large cohort of patients undergoing nephrectomy for localized ccRCC to evaluate the association of PBC with tumor expression of PDL1. Secondarily, we examine the association of PBC and relapse free survival (RFS) after adjusting for age and PDL1 expression. Methods: Through chart review, we obtained PBC values at time of nephrectomy for patients enrolled in the Mayo Clinic Renal Registry from 1990-2009 who were treated for localized (M0) ccRCC including the following: hemoglobin (HGB), white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute eosinophil count (AEC), absolute monocyte count (AMC), and platelets (PLT). We determined tumor PDL1 expression as a continuous variable (% of positive PDL1 tumor cells) using the 5H1 antibody on archived tissues. We analyzed the correlation of PBC values with PDL1 expression as a continuous variable using a linear estimate. To evaluate the association of PBC values with RFS after adjusting for PDL1 expression, we employed multivariate Cox regression models. Results: A total of 706 ccRCC patients had available PDL1 expression and PBC. PDL1 expression was inversely associated with HGB (linear estimate of -0.02, p&lt;0.001) and positively associated with platelets (linear estimate 1.73, p&lt;0.001) whereas there was no association with PDL1 with WBC, ANC, AEC, or AMC. After adjusting for age and PDL1 expression, a higher HGB (HR=0.87, p&lt;0.001), higher ALC (HR 0.68, p=0.003), and higher AEC (HR 0.12, p=0.002) were all associated with improved relapse free survival. Conversely, higher PLT was associated with decreased RFS (HR 1.002, p&lt;0.001). Conclusions: PDL1 expression is associated with decreased HGB and increased PLT at the time of nephrectomy. After adjusting for PDL1 expression and age, higher HGB, ALC, and AEC are associated with improved RFS, while higher platelets are associated with decreased RFS.
Phase Ib study of pembrolizumab in combination with bevacizumab for the treatment of metastatic renal cell carcinoma: Big Ten Cancer Research Consortium BTCRC-GU14-003.
Authors: Arkadiusz Z. Dudek, R. Alejandro Sica, Amer Sidani, Gautam Gopalji Jha, Hui Xie, Ajjai Shivaram Alva, Mark N. Stein, Eric A. Singer
Journal: Journal of Clinical Oncology (2016)

559 Background: Renal cell carcinoma (RCC) tumor vasculature is abnormal and does not provide nutritive blood flow, which results in regions of hypoxia. This hypoxia contributes to the immune tolerance of tumor cells by impeding the homing of cytotoxic T cells into tumor parenchyma. In addition, tumor angiogenesis enhances activity of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that suppress innate anti-cancer immunity. It has been demonstrated in preclinical models that antiangiogenic therapy decreased the number of MDSCs and changed polarization of TAMs from an immunosuppressive (M2-like) to an immunostimulatory (M1-like) phenotype. We hypothesized that therapy with bevacizumab will normalize the tumor vasculature, promote M1-like phenotype of TAMs, and thus potentiate the immunotherapeutic activity of pembrolizumab. As a prerequisite to testing this hypothesis, the objective of this study was to establish the safe dose of bevacizumab when used in combination with pembrolizumab. Methods: Our subject population included males and females (age &gt; 18 y) with metastatic clear cell RCC after failure of at least one systemic therapy. In this Phase Ib dose escalation study, pembrolizumab (200 mg fixed dose every 3 weeks) was given in combination with bevacizumab (either at 10 mg/kg or 15 mg/kg every 3 weeks). The primary endpoint was to establish the maximum safe dose. Results: 12 subjects have been enrolled: 10 males (ages 33-68 y, mean: 52.7, median: 54.5) and 2 females (ages 61 and 62 y). To date 3 patients have received 1 cycle; 2 patients have received 2, 3, and 4 cycles each; and there are single patients who have received 5, 6, and 7 cycles each. No dose-limiting toxicity or serious adverse events related to the study drug have been reported. There were no grade 3 or 4 drug-related toxicities noted, and the most common grade 1 and 2 toxicities were diarrhea, fatigue, fever, hypertension, nausea, rash, and rigors. Conclusions: The 200 mg fixed dose of pembrolizumab and 15 mg/kg dose of bevacizumab, both given every 3 weeks, was determined to be safe and recommended for a multicenter Phase 2 study that is ongoing. Clinical trial information: NCT02348008.
Predictive value of mean apparent diffusion co-efficient value for responsiveness of temozolomide-refractory malignant glioma to bevacizumab.
Authors: M. Nagane, K. Kobayashi, M. Tanaka, K. Tsuchiya, Y. Shiokawa
Journal: Journal of Clinical Oncology (2011)

e12517 Background: Current standard care of newly-diagnosed glioblastoma (GBM) is maximum safe resection followed by temozolomide (TMZ) concurrent to and after RT, but on relapse, no standard chemotherapeutic regimens have yet been established. We treated patients with recurrent GBM post-TMZ with bevacizumab (BV), a potent anti-VEGF monoclonal antibody, and a predictive value of measuring apparent diffusion coefficient (ADC) for BV response is presented. Methods: Nine patients with post-TMZ recurrent or progressive high grade gliomas [7 GBMs and 2 anaplastic astrocytomas (AA)] were treated with BV monotherapy at 10mg/kg biweekly since August 2009. Five patients underwent RT plus concomitant TMZ at the initial therapy. The average patient age was 57 (22-78), and median Karnofsky Performance Scale (KPS) was 70 (30-90). The median BV line number was 2 (2-5). Two cases had undergone additional stereotactic radiotherapy within 6 months prior to BV. The response was determined according to the Macdonald criteria. The first MRI after BV therapy was performed within 2 weeks. A mean ADC value (mADC) of gadolinium-enhanced tumor contours was calculated using the Picture Archiving and Communication System in Kyorin University Hospital. Results: After the first BV cycle, early post-treatment MRI demonstrated a decrease of evaluable tumor volume in eight of nine cases (88.9%). Partial response was obtained in four cases (44.4%), and other four cases remained at stable disease. Among a total of 15 individual evaluable enhancing lesions, 11 tumors shrank, while four did not respond. mADC values were above 1,100 (10-6mm2/sec) in all of the responding tumors, in contrast those in all non-responding lesions scored below 1,100 (p=0.001). mADC values decreased after the first BV treatment in all lesions except for one that did not respond. KPS improved immediately in four cases (44.4%). Median progression-free survival was 2.2 months. Conclusions: BV monotherapy is active for patients with TMZ-refractory recurrent gliomas leading to rapid lesion shrinkage and symptom relief at a high rate. The tumor mADC value may be of useful marker for prediction of BV response and thus patient selection.