tbuckley/cabot-search huggingface dataset:
Building clinical volumes, research capacity, and quality care in testicular cancer.
Authors: Craig R. Nichols
Journal: Journal of Clinical Oncology (2013)

198 Background: Developing consistent, evidence-based, personalized and cost appropriate management of germ cell tumors is challenging for two reasons: these are uncommon diseases and successful management requires nuanced input from many disciplines with specialized interest in germ cell tumors. We speculated model combining a working tumor board and a true multidisciplinary clinic would improve volumes, research contributions, consistency and personalized care for patients with germ cell tumors. Methods: Beginning in March 2011, we developed a multidisciplinary clinic model, flow and communications with the following principles in mind. 1.) embed electronic capacity to capture clinical and biological datasets to serve as a template for research collaborations with national and international colleagues, 2.) coordinate clinical operations around a mandate for expert pathological and radiographic review, 3.) develop and apply evidence-based clinical guidelines, 4.) build an “open-source” operation and accept cases for electronic review and deliberation from patients and providers who desired expert oversight from an experienced team. Results: Our current clinical volumes have grown to an average of two new cases/week along with 1-2 outside reviews. Ongoing follow-up patients average 10/week. RPLND volumes have increased markedly to more than 20/year. All cases undergo pathology and radiology review. Adherence to published guidelines is superb with few deviations. Imaging schedules have been scaled down to approximately one third of previous radiation exposure. Research contributions have increased with the development of international collaborations, publications and new investigator-initiated studies. Conclusions: Our results demonstrate that purposeful coordination and consolidation of expertise and interests can result in the development of regional and national resources for management of rare malignancies such as testicular cancer. These high functioning clinics result in cost-effective, evidence-based management and high patient satisfaction.
Intraoperatively assessed macroscopic serosal changes in patients with curatively resected advanced gastric cancer (GC): Clinical implications for prognosis and peritoneal recurrence.
Authors: Changhoon Yoo, Min-Hee Ryu, Heung-Moon Chang, Jeong Hwan Yook, Young Soo Park, Baek-Yeol Ryoo, Sook Ryun Park, Sung Tae Oh, Byung Sik Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2015)

23 Background: To validate the prognostic relevance of macroscopic serosal changes in patients with resected GC, we analyzed prospectively collected databases of two multicenter randomized phase III trials on adjuvant chemotherapy. Methods: In total, 655 patients in the control groups of AMC 0101 (NCT00296322) and 0201 (NCT00296335) trials were selected. Macroscopic serosal changes were determined according to disruptions in serosal continuity, such as changes in color or nodular texture by the operating surgeon. Correlations with recurrence-free survival (RFS), overall survival (OS), and time-to-peritoneal recurrence were analyzed. Results: About two-thirds of the patients were male (69%), and the median age was 55 years (range = 29–70 years). According to Lauren’s classification, 215 patients (33%) showed intestinal type. After a median follow-up period of 61.6 months (range = 2.6–113.9 months), the 5-year RFS and OS rates were 55.0% (95% CI = 51.2–58.9%) and 59.9% (95% CI = 56.2–63.6%), respectively. Intraoperatively assessed macroscopic serosal changes were identified in 432 patients (66%). This was significantly associated with multifocal or diffuse gastric cancer (p = 0.001), Borrmann type IV (p = 0.005), advanced pathological T stage (p &lt; 0.001), advanced pathological N stage (p &lt; 0.001), advanced pathological stage (p &lt; 0.001), and total gastrectomy (p &lt; 0.001). In multivariate analyses, which included prognostic factors of localized gastric cancer, macroscopically serosal changes were significantly associated with poor RFS (hazard ratio [HR] = 2.0, 95% CI 1.4–2.7; p &lt; 0.001) and OS (HR = 2.1, 95% CI 1.5–3.0; p &lt; 0.001). It was also significantly related with shorter time-to-peritoneal recurrence (HR = 2.9; 95% CI = 1.7–5.0; p&lt; 0.001). Conclusions: Intraoperatively assessed macroscopic serosal changes confer a poor prognosis and increased peritoneal recurrence in patients with curatively resected GC. Macroscopic assessment of serosal changes may be a useful indicator that allows better risk stratification of patients with resected GC in terms of prognosis and peritoneal recurrence.
Neoadjuvant treatment response and outcomes in locally advanced rectal cancer: Establishing oncologic benchmarks.
Authors: G. J. Chang, I. J. Park, Y. N. You, C. Hu, S. R. Hamilton, C. Eng, B. W. Feig, P. Das, S. Krishnan, C. H. Crane, S. T. Nguyen, M. A. Rodriguez-Bigas, J. M. Skibber
Journal: Journal of Clinical Oncology (2011)

3545 Background: Neoadjuvant chemoradiotherapy (CXRT) for rectal cancer is associated with improved local control and may result in complete tumor response (pCR). Associations between tumor response at resection and disease control should be established before response is used to inform organ-preserving treatment strategies. The aim of this study was to compare oncologic outcomes associated with pathologic response after CXRT. Methods: We performed a retrospective consecutive cohort study of all patients diagnosed 1993-2008 with cT3-4 or cN+ (by EUS, CT, or MRI) rectal carcinoma and treated with preoperative CXRT and resection. Rates of disease-free survival (DFS), distant metastasis (DM), and local recurrence (LR) were compared among patients with complete (ypT0N0), intermediate (ypT1-2N0), or poor (>ypT1-2N0) response. Results: 749 patients met criteria and were classified by tumor response: complete (129, 17.2%), intermediate (208, 27.7%), or poor (388, 51.8%). Age, sex, cN, and tumor location were not related to tumor response. Poor response was associated with higher cT stage (P<.0001). 5-year DFS was associated with tumor response: 93.5% vs. 85.0% vs. 64.4% (P<.0001) for complete, intermediate, and poor response, respectively. 5-year OS (92.7% vs. 90.9% vs. 80.4%; P=.001), DM (5.7% vs. 14.4% vs. 29.5%; P<.0001), and LR rates (1.8% vs. 2.7% vs. 8.8%; P=0.0048) were also different (complete vs. intermediate vs. poor response, respectively). Presence of residual lymph node metastases after preoperative CXRT (ypN+) was correlated with higher ypT stage (P<.0001). DFS was associated with yp-stage (P<.0001), but not with clinical stage (P=0.234). Conclusions: Oncologic outcomes after preoperative chemoradiotherapy and resection for rectal cancer is dependent upon treatment response. These data provide oncologic benchmarks to which novel organ preserving treatment strategies should be compared. Variables Complete response Intermediate response Poor response P value 5-year OS % 92.7 90.9 80.4 .001 5-year DFS % 93.5 84.9 65.7 <.0001 5-year DM % 5.7 14.4 29.5 <.0001 5-year LR % 1.8 2.7 8.8 .0048
A phase II trial of docetaxel, cisplatin plus 5-fluorouracil (DCF) as first-line therapy in patients with metastatic or locally advanced inoperable gastric adenocarcinoma
Authors: M. S. Reza, M. A. Hai, Q. Chowdhury
Journal: Journal of Clinical Oncology (2008)

15620 Background: Docetaxel is increasingly integrated into chemotherapy combination regimen against Gastric cancer. To improve the poor prognosis of patients (Pts) with metastatic or advanced Gastric cancer, we conducted a phase II trial to evaluate the efficacy and tolerability of DCF. Methods: From January 2002 to December 2005, 32 pts with; histologically/ cytologically proven, bidimensionally measurable locally advanced or metastatic Gastric adenocarcinoma, age 18 ∼ 75 years with ECOG performance status 0 ∼3, no prior chemotherapy, life expectancy > 3 months, adequate bone marrow, renal, hepatic and haematological values were enrolled. It was an open- labeled, non- randomized, multi- centered and prospective study.The treatment protocol was intravenous infusion of Inj. Docetaxel 75 mg/m2 day 1, Inj. Cisplatin 30 mg/m2 days 1 - 3 and Inj. 5-Fluorouracil 500 mg/m2 days 1 - 3 at an interval of 3 weeks. The efficacy was measured by responses rates and safety was measured by adverse events and laboratory blood values. Results: This trial consisted of 22 (68.75%) male and 10 (31.25%) female pts. Median age was 54 years. 18 (56.25%) pts were inoperable locally advanced and the remaining 14 (43.75%) were metastatic diseases where 9 hepatic and 5 pulmonary. In total, 168 cycles chemotherapy were administered with an median of 5.25 cycles per pt and 30/ 32 pts were evaluated for responses. The overall response was 20 (66.67%) with 4 complete and 16 partial responses. 7 (23.33%) pts had stable diseases and 3 (10%) had progressive diseases. Overall survival was 10.5 months. Grade 3 haematological toxicities were observed as follows: neutropenia 32%, anaemia 20% and thrombocytopenia 6%. Some non- haematolocal toxicities including nausea 40%, vomiting 25%, mucositis 18%, diarrhoea 20% and peripheral neuropathy 10% were observed. No febrile neurtropenia and fatal events were recorded. Conclusions: This phase II trial supports the use of DCF combination in chemo naïve pts with metastatic or locally advanced inoperable Gastric adenocarcinoma due to its very promising anti - tumor activity with well-tolerated toxicities. No significant financial relationships to disclose.
Factors affecting survival in women with ductal carcinoma in situ (DCIS): Race and the delivery of adjuvant radiotherapy.
Authors: Elisabeth E. Arrojo, Alvaro Martinez, Eduardo Fernandez, Jeffrey D. Forman, Michael Ghilezan, Frank A. Vicini
Journal: Journal of Clinical Oncology (2016)

29 Background: Recent publications questioned the survival impact of adjuvant radiotherapy (A-RT) in the treatment of DCIS. These reports had in common a short follow up. We wanted to know, in a disease where long term follow up is required, the magnitude of improvement in survival and assess any correlation with race and income. Methods: Search in the Surveillance, Epidemiology and End Results database, of patients diagnosed with DCIS between 1988 and 2012, younger than 70 years old. Analyses of age, race, hormonal receptors (HR), tumor size, surgery, ART and household income. Survival analyses with Kaplan-Meier and multifactorial with Cox proportional-hazard regression. Results: 125,805 patients. Mean follow-up 7.9 years. Patients treated with A-RT resulted in a mortality by breast cancer (DBC) significantly lower (-1.10%; HR: 0.54 [IC95%:0.48-0.59]; p &lt; 0.0001). Based on the type of surgery, mastectomy resulted on a DBC significantly higher than those treated with tumorectomy and A-RT (+1.15%; HR: 2.08 [IC95%:1.84-2.36]; p &lt; 0.0001). Patients with HR+ presented a significantly lower DBC. Black race was the one with the lowest household income (43% &lt; 53900$) opposite to the Asian which was the one with the highest (47% &gt; 71520$). Black race, also presented a DBC significantly higher than the other ones. In the multifactorial analyses (see table), the only variables which presented a significantly influence in DBC were -ART (it decreases DBC) and race (black race increases DBC). Conclusions: These results show blacks, which are the ones with lowest household income, have a significantly increase in cancer mortality than the other races, and that A-RT cuts mortality rates quite drastically in women with DCIS. [Table: see text]
A Novel mTOR Kinase Inhibitor Causes Growth Inhibition, Cell Cycle Arrest, Apoptosis and Autophagic Cell Death in Mantle Cell Lymphoma Cell Lines: A Distinct Profile from Rapamycin.
Authors: Weiming Xu, Christine Kang, Mercedes Delgado, Sophie M Perrin-Ninkovic, Patrick W Papa, Jennifer R Riggs, John Sapienza, Ronald J Albers, Branden G.S Lee, Roy L Harris, Deborah S Mortensen, Peter Worland, Sabita Sankar
Journal: Blood (2008)
Network wide national and international radiation oncology accreditation program.
Authors: Andrew S. Kennedy, Tammy Wotring, Zejian Liu, Howard A. Burris, Charles F. LeMaistre
Journal: Journal of Clinical Oncology (2014)

271 Background: Modern radiation oncology departments contain an extensive array of complex therapies and technologies. Adoption of new treatments and staff changes challenge each team in maintaining high levels of performance and standards. Fewer than 15% of US centers have independent certification of quality. We plan to achieve American College of Radiology (ACR) Accreditation for all USA and UK Radiation Oncology Centers of HCA. Methods: A GAP analysis tool was developed to enable each center to approach the ACR application with the coordinated and simultaneous efforts of all sections of the radiation oncology department. Data was prospectively gathered for each department, highlighting areas of strength and aspects that need focused attention to improve. A scale of 1-5 was assigned to each task regarding the initial and ongoing level of progress towards meeting the standard with documentation for each required. Our intent is for each of the 52 radiation oncology departments to achieve full ACR Accreditation in a timeframe of no more than 4.5 months from start of the GAP analysis. Results: One program was fully accredited when the program began in July 2013. Since then 6 have achieved full accreditation and 12 are in process with the GAP tool. Analyses of full GAP data are available from eight programs thus far. High achievement in compliance with ACR Standards (95-100% compliance) was found in policies monitoring complications, adverse reactions and ‘time out’ procedures. Areas needing improvement s (&lt;80% compliance) included annual review of policies and procedures, physician peer review, formal treatment planning system QA and imaging equipment quality control. Our facility in London will be the first achieving ACR accreditation in the UK. Conclusions: Significant time savings, engagement of staff, and accreditation success has thus far been realized with the utilization of a GAP tool for radiation oncology program accreditation. Common deficiencies were identified across facilities and allowed sharing of successful corrective action plans. The success of the program in improving quality led to the adoption of the ACR program from our USA sites to our radiation oncology departments in the UK.
Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).
Authors: Christoph W. Reuter, Michael A. Morgan, Martin Fenner, Viktor Grünwald, Arnold Ganser
Journal: Journal of Clinical Oncology (2013)

e16024 Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Carboplatin, docetaxel and steroids interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone blood levels was analyzed. Methods: Docetaxel failure/resistance was defined as disease progression during docetaxel treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC patients (pts.) were treated with at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 plus docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) every 4 weeks and prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT levels were measured before (n=51) and during DC chemotherapy (n=41). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 36/74 (48.6%) pts. At the current analysis the median follow-up time was 16.6 months and 56/74 pts. had died. Median progression-free survival (PFS) was 6.9 months (CI 95% 5.9, 7.9) and median overall survival (OS) was 18.6 months (CI 95% 12.4, 24.7). Median nadir FT levels were 2.8 pmol/L before and below the RIA detection limit of 0.6 pmol/L during DC treatment (p=0.008). While only 4/51 pts. had FT levels &lt;0.6 pmol/L before DC treatment (all under abiraterone therapy), 28/41 pts. had nadir FT values &lt;0.6 pmol/L during DC chemotherapy (p&lt;0.0001). Median FT levels &lt;0.9 pmol/L during DC treatment were associated with a higher PSA response rate (hazard ratio HR 0.19; CI 0.05, 0.78, p=0.021) and a higher OS (HR 0.34; CI 0.15, 0.81, p=0.015). FT remained statistically prognostic in multivariable analyses. The DC regimen was reasonably well tolerated, with leukopenia/ neutropenia as the most common reversible grade 3/4 toxicity (41.9/37.8%). Conclusions: These data demonstrate for the first time that FT is an important prognostic factor for PSAR and OS in mDRPC pts. during chemotherapy.
Pretargeted radioimmunotherapy significantly improves the treatment of non-Hodgkin’s lymphoma in a nude mouse model
Authors: R. M. Sharkey, H. Karacay, P. Y. Brard, C. H. Chang, W. J. McBride, I. D. Horak, D. M. Goldenberg
Journal: Journal of Clinical Oncology (2005)

2548 Background: Radioimmunotherapy (RAIT) is an approved treatment of follicular and transformed non-Hodgkin’s lymphoma (NHL) that uses anti-CD20 IgGs radiolabeled with 90Y or 131I. Administered in cases of refractory disease, there are a number of new trials assessing the prospects for expanding the indication for this treatment. Our studies suggest that significant improvements in the therapy of NHL could be obtained by using a bispecific antibody (bsMAb) pretargeting procedure that enhances the therapeutic window for targeted radionuclides compared to directly radiolabeled IgG. Methods: Nude mice bearing 1.0- to 1.5-cm diameter s.c. human Ramos B-cell lymphoma xenografts were administered a bsMAb composed of the Fab’ fragment of a humanized anti-CD20 MAb (hA20) for tumor localization coupled to the Fab’ of a novel anti-hapten (HSG) antibody for binding a 90Y-labeled HSG-peptide. Forty-eight hours later, a treatment of 0.5 or 0.8 mCi of 90Y-HSG-peptide was given. The pretargeting procedure was compared to equitoxic amounts of 90Y-hA20 IgG (e.g., 0.105 and 0.175 mCi, respectively), 0.8 mCi of 90Y-HSG-peptide alone, or to untreated animals. Results: Biodistribution studies showed tumor uptake of the 90Y-anti-CD20 IgG did not exceed the level of radioactivity in the blood until 7 days after injection, whereas tumor/blood ratios for the pretargeting procedure where 3:1 within 3 h and 30:1 within 24 h. Tumors in animals given 0.8 mCi of the 90Y-HSG-peptide alone progressed as rapidly as in the untreated group, while pretargeting was more effective at controlling and even curing animals than the 90Y-hA20 IgG. In several studies with 6 months of observation, the pretargeting procedure has cured ≥50% of the animals compared to ≤ 10% for the 90Y-hA20 IgG. Conclusions: Time to disease progression and survival analyses showed pretargeting to be significantly better (P < 0.005) than the directly radiolabeled antibody treatment. This suggests that a humanized bsMAb pretargeting procedure could be a more effective treatment of NHL than currently available directly radiolabeled antibodies. (Supported in part from DOE grant DE-FG02-95ER62028 and the Thomas & Agnes Carvel Foundation.) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IBC Pharmaceuticals, Immunomedics Immunomedics
Thromboembolic events with cisplatin-based neoadjuvant chemotherapy for transitional cell carcinoma of urinary bladder.
Authors: Joanne Botten, Matt Sephton, Tania Tillett, Susan Masson, Narottam Thanvi, Christopher Herbert, Serena Hilman, Edward Rowe, David Gillatt, Raj Persad, Tim Whittlestone, Amit Bahl
Journal: Journal of Clinical Oncology (2013)

277 Background: Cancer is associated with an increased risk of venous and arterial thrombo-embolic events (TEEs), including deep vein thrombosis, pulmonary embolism, cerebrovascular accident and unstable angina/myocardial infarction. Several factors are known to influence the incidence of TEEs including chemotherapy agents, particularly cisplatin. Czaykowski et al reported 12.9% of patients receiving multiagent cisplatin based chemotherapy for transitional cell carcinoma between 1986 and 1996 developed TEE. Moore et al found that the rate of TEE in a similar cohort of patients receiving the same treatment to be 18.2% (6/33 patients). Methods: Retrospective case note review from an electronic database of patients allocated a cisplatin based neo-adjuvant chemotherapy regimen for transitional cell carcinoma of the bladder between April 2009 and April 2012. TEE was recorded as a chemotherapy related event if it occurred between the first dose of cisplatin and 4 weeks after the last administered dose. Results: 44 received treatment in the neoadjuvant setting. 11 out of 44 patients (25%) receiving neo-adjuvant chemotherapy developed TEE. 7 out of these 11 patients were male, 4 were female. 9 of the 11 TEEs (82%) in the neoadjuvant setting were arterial or peripheral arterial thrombi, including pulmonary emboli and thrombi within the aorta, left ventricle and iliac arteries. 5 of these thrombi were asymptomatic and only discovered on routine scanning. 2 out of the 11 TEEs were leg deep vein thromboses – both of which were symptomatic. 64% of TEEs occurred after the second cycle of cisplatin, the remainder after the third cycle. Conclusions: Neo-adjuvant chemotherapy is being adopted as the standard of care for patients with muscle-invasive TCC of bladder. The higher rate of TEE in our series compared to previous publications probably reflects the asymptomatic TEE being diagnosed on scans done for assessing response to chemotherapy. The significant rates of TEEs in this setting highlights the need to consider this complication as it may have a bearing on outcome from treatment, in particular delay in radical cystectomy.