tbuckley/cabot-search huggingface dataset:
Phase II trial of combination therapy of tumor lysate-pulsed dendritic cells and adoptive transfer of anti-CD3 activated T cells (DC/VAC) to lower postsurgical recurrence rates of cholangiocellular carcinoma (CCC)
Authors: K. Shimizu, N. Takeshita, Y. Kotera, K. Yoshitoshi, S. Ariizumi, S. Katagiri, T. Otusbo, M. Yamamoto, K. Takasaki, A. Aruga
Journal: Journal of Clinical Oncology (2008)

3068 Background: Postsurgical recurrence of CCC is frequent and fatal. This phase II study investigated the efficacy and safety of DC/VAC in patients (pts) who underwent curative resection for CCC to lower postsurgical recurrence rates. Methods: Patients (pts) with CCC who underwent curative resection received DC/VAC. DC/VAC consisted of dendritic cells with autologous lymphocytes activated with interleukin-2 and antibody to CD3 at 14-day intervals for 3 months. The immune responses to tumor antigens (Tgs) were monitored by delayed- type hypersensitivity (DTH). The primary endpoint was relapse-free survival (RFS). Secondary endpoints were overall survival (OS), the monitoring of immune responses to Tgs, and toxicity. Results: Between September 2000 and August 2005, 26 pts were included, with a median age of 61.4 years, a median tumor size of 5.8 cm. Twenty-five pts (96 %) underwent segmentectomy. On the pathological findings, vascular invasions, intrahepatic metastases (IM), and lymph node involvements (LNM) were 77 %, 27 %, and 50 %, respectively. The median RFS was 7.4 months. Eight pts showed positive DTH responses to Tgs. Among these pts, the median PFS was 22.5 months. Conclusions: This result suggests that DC/VAC is very effective in pts with positive DTH responses to Tgs who underwent curative resection for CCC to lower postsurgical recurrence rates. No significant financial relationships to disclose.
Introducing medical students to survivorship care through an elective oncology summer program.
Authors: Ryan Patrick McKillip, Olwen Mary Hahn, Carol A. Rosenberg, Olufunmilayo I. Olopade, Vineet M Arora, Daniel William Golden
Journal: Journal of Clinical Oncology (2017)

17 Background: Advancing the quality of cancer care requires that physicians be trained in survivorship care. An oncology seminar series was designed and implemented for first year medical students (MS1s) to improve their knowledge of oncologic disciplines, including survivorship care, by educating them about these disciplines from both a research and clinical perspective. Methods: In 2015 and 2016, MS1s at a single US medical school were invited to participate in the Scholars in Oncology-Associated Research (SOAR) summer program, which included a series of 10 lectures to provide a general survey of how clinical care, basic sciences, and social sciences apply to oncology as a multidisciplinary specialty. Lectures included topics specific to cancer genetics, medical, surgical, and radiation oncology, hospice/palliative medicine, and survivorship care. The students also attended a multidisciplinary tumor board and had the opportunity to shadow a pharmacist, radiation therapist, or palliative care advanced practice nurse. Students completed self-assessments of their understanding of oncology and its related disciplines before and after SOAR. Likert-type scores were 1=not at all, 2=somewhat, 3=moderately, 4=quite, and 5=extremely and are reported as median [interquartile range]. Results: Twenty-seven students successfully completed SOAR. Thirty-three pre- and 25 post-assessments were completed. Student self-reported understanding of oncology as a clinical discipline (2[2-3] vs. 4[4-4] p&lt;.01) and as a research discipline (2[2-3] vs. 4[4-4] p&lt;.01) improved after SOAR. Student understanding of survivorship care as a clinical discipline (1[1-2] vs. 3[2-4] p&lt;.01) and as a research discipline (1[1-1] vs. 2.5[2-3] p&lt;.01) also improved. All students indicated they would be "quite" or "extremely" likely to recommend SOAR to future students. Conclusions: A structured didactic introduction to oncology, SOAR, was successfully piloted. MS1s report improved understanding of oncology and survivorship care as clinical and research disciplines. Additional curricular content is required during subsequent years to further improve student understanding of oncology and survivorship care.
Genomic Instability in CML-CP originates From the Most Primitive Imatinib-Refractory Leukemia Stem Cells
Authors: Elisabeth Bolton, Mirle Schemionek, Hans-Urlich Klein, Grazyna Hoser, Sylwia Flis, Thoralf Lange, Linda Kerstiens, Margaret Nieborowska-Skorska, Martin C. Müller, Hardik Modi, Ravi Bhatia, Steffen Koschmieder, Tomasz Skorski
Journal: Blood (2012)
Rates of pathologic complete or near complete response following neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer.
Authors: Michael Chuong, Eric Albert Mellon, Sarah Hoffe, Ravi Shridhar, Gregory M. Springett, Pamela Joy Hodul, Mokenge Peter Malafa, Nicholas Figura, Barbara Centeno
Journal: Journal of Clinical Oncology (2013)

221 Background: While the clinical response from induction chemotherapy followed by stereotactic body radiation therapy (SBRT) has been reported for borderline resectable pancreatic cancer (BRPC) patients, response from a histopathologic standpoint has not been described. Methods: This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by 5-fraction SBRT. All patients were restaged and underwent resection. A pathologist (B.C.) specializing in pancreatic cancer reviewed each surgical specimen and assigned two Tumor Regression Grade (TRG) scores, one from the College of American Pathologists (CAP) and one from the MD Anderson Cancer Center (MDACC). Overall survival (OS) and progression free survival (PFS) were correlated to TRG score using the Kaplan-Meier method. Results: This study evaluated 35 resected BRPC patients with a median follow up of 13.8 months (range, 6.1-24.8). All received induction gemcitabine-based chemotherapy, most commonly GTX (gemcitabine, docetaxel, capecitabine) (82%), followed by 5-fraction SBRT with a median 35 Gy (range, 30-40). TRG scores according to the CAP were as follows, from best to worst response: 0 (n=3), 1 (n=13), 2 (n=15), and 3 (n=4). TRG scores according to MDACC were as follows, from best to worst response: IV (n=3), III(M) (n=6), IIB (n=11), IIA (n=10), and I (n=5). Any neoadjuvant treatment effect according to MDACC scoring (IIA-IV vs. I) was associated with improved OS and PFS (both p=0.019). Conclusions: This study demonstrated a significant pathologic response with a gemcitabine based neoadjuvant regimen containing SBRT and suggests a survival benefit based on response as measured by the MDACC scoring system.
Predicting radical prostatectomy outcome: Cell cycle progression (CCP) score compared with primary Gleason grade among men with clinical Gleason less than 7 who are upgraded to Gleason 7.
Authors: Matthew R. Cooperberg, Stephen J. Freedland, Thorsten Schlomm, Julia E. Reid, Steven Stone, Michael K. Brawer
Journal: Journal of Clinical Oncology (2014)

13 Background: Improved prognostic markers for prostate cancer are an important part of addressing the issue of over- and under-treatment in prostate cancer. Gleason score (GS), prostate-specific antigen and clinical stage work well for population risk assessment but lack precision for individual patients. Concern over undergrading on biopsy is felt to be a major barrier to increasing use of active surveillance. Molecular analysis can further refine risk assessment as demonstrated by the cell cycle progression (CCP) score (Prolaris) which has been shown to predict prostate cancer aggressiveness in eight separate cohorts. In these studies, CCP scores typically ranged from −2 to +3 with each one−unit increase in CCP score corresponding to approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In the present investigation, we sought to assess how upgrading compared with CCP in predicting failure after radical prostatectomy (RP). Methods: In this study, we examined men from three cohorts (UCSF, Martini Clinic, and Durham VAMC) with clinical GS (cGS) less than 7 who had pathologic GS (pGS) 3+4 or 4+3. The CCP assay was performed using RP specimen from UCSF and biopsy material from the other cohorts. We compared the rates of biochemical recurrence (BCR) as predicted by pGS, CAPRA, or CCP score alone versus CAPRA combined with CCP score using a Cox proportional hazards model stratified by cohort. Results: Among the 230 men with cGS less than 7 and pGS equal to 7 included in this analysis, 207 had pGS 3+4 and 57 had BCR; 23 had pGS 4+3; and eight had BCR. There was no difference in BCR based on GS (p=0.8) or CAPRA (p=0.4). In contrast, CCP score alone and a pre-defined score combining the CCP score and CAPRA were prognostic of BCR (HR=1.82 [95 % CI 1.32-2.52; p&lt;0.001]; HR=1.84 [95 % CI 1.10-3.05; p=0.021] respectively). Conclusions: These data indicate that the risk of BCR is indistinguishable in men with cGS less than 7 who have pGS 3+4 or 4+3. However, the CCP assay does provide stratification of this risk. Tests that can predict BCR on biopsy will aid in initial therapeutic decision making.
A single institute retrospective trial of concurrent chemotherapy with SIR-Sphere versus SIR-Sphere alone in patients with chemotherapy-resistant colorectal cancer liver metastases.
Authors: May Thet Cho, Jonathan Kessler, John Park, Gagandeep Singh, Yi-Jen Chen, Philip HG Ituarte, Marwan Fakih
Journal: Journal of Clinical Oncology (2016)

770 Background: The use of selective internal radiation therapy (SIRT) with SIR-Spheres in chemotherapy-resistant colorectal cancer liver metastases (CRC-L) has been associated with favorable progression free survival (PFS) and overall survival (OS) when given alone or concurrently with chemotherapy. However, no prospective studies exist for concurrent SIRT and chemotherapy (SIRT-CT) vs. SIRT alone. We conducted a single institute retrospective trial to compare the effect of SIRT-CT to SIRT alone on liver PFS in patients with CRC-L. Methods: Patients (pts) with CRC-L treated with SIR-Spheres at City of Hope between 2009 and 2014 were identified. CRL-L patients treated with SIRT-CT or with SIRT were excluded if they received, following radioembolization, any chemotherapy/targeted regimen on which they did not previously progress. This strategy was adopted to minimize the impact of post-SIRT systemic therapy bias on SIRT-CT/SIRT liver PFS outcome. Pts characteristics included demographics, liver involvement pattern, and lines of prior chemotherapy. Liver PFS, response rate, and toxicities were compared between SIRT-CT and SIRT arms. Kaplan-Meier estimation was used for PFS analysis. Results: 48 CRC-L pts were treated with SIR-spheres; 27 satisfied the post-SIR-spheres systemic treatment criteria (14 SIRT-CT, 13 SIRT) and were included on this study. Pts characteristics included: age (median = 62; range 52-80), sex (18 males), primary site (colon: 23), hepatic disease burden (23 bilobar), 5-FU resistance/intolerance (25/2), and extrahepatic disease (22). Pts characteristics were similar between treatment arms, except for median prior therapies (SIRT-CT = 3, SIRT = 2). No SIRT-CT or SIRT associated ≥ grade 3 toxicities were noted. Disease control rates were 84% (2/13 PR; 9/13 SD) and 14% (2/14 SD on the SIRT-CT and SIRT arms, respectively (p = 0.001). Median PFS in the liver was 176 days in the SIRT-CT group vs. 91 days in the SIRT group (p = 0.0006). Conclusions: In patients with 5-FU refractory CRC-L, SIRT-CT is associated with an increased disease control rate and a prolonged DFS in comparison with SIRT alone.
Ensuring head and neck oncology patients receive recommended pretreatment dental evaluations.
Authors: Danielle Nina Margalit, Stephanie Losi, Roy B. Tishler, Jonathan Daniel Schoenfeld, JoAnn Fugazzotto, Josie Stephens, Amy Cebulski, Elizabeth Hammerstrand, Laura Ma, Holly Lopes, Robert I. Haddad, Nathaniel S. Treister, Jennifer L. Frustino
Journal: Journal of Clinical Oncology (2014)

100 Background: Pre-treatment dental evaluations are recommended for head and neck (H&amp;N) cancer patients (pts) prior to radiation therapy (RT) to minimize the risk of acute and long-term side effects of treatment. We previously created a dental instructional guide (DIG) outlining the necessary components of the pre-radiation dental evaluation for pts undergoing community-based dental evaluation. Yet our program did not have a system for documenting which pts received the DIG. We aimed to create a system to ensure that pts are given the DIG early in their care-plan and that such pts are readily identifiable so we can follow-up and confirm that the recommended dental care is complete prior to starting RT. Methods: Chart review was performed to determine the percentage of eligible pts with documented provision of the DIG. A diagnostic survey of H&amp;N oncology clinicians was analyzed with a Pareto chart to determine common barriers to DIG provision and documentation. Clinicians were surveyed on potential ways to document DIG provision to eligible pts. The Model for Improvement and DMAIC (Six Sigma) methodologies were used and multiple Plan-Do-Study-Act (PDSA) cycles were performed to implement the intervention and monitor change. Change data was analyzed using a P-chart, 3-sigma. Results: We used a process map to identify 3 potential care-plans within the H&amp;N oncology program and assist in defining which providers had primary responsibility for providing the DIG. We then designed and implemented a template within the electronic medical record that documents the clinician who gave the DIG and the date it was given. There was an improvement in the rate of DIG documentation from a baseline of 0% (range 0-0%) to a mean of 40% (range 0-100%) over 3-months (p&lt;0.01). This improvement was sustained through last follow-up at 5 months. Conclusions: Through a multidisciplinary approach, we implemented an intervention to identify pts undergoing community-based dental evaluation prior to RT for H&amp;N cancer. Further efforts are focused on increasing the DIG documentation rate and increasing our interaction with community dentists to promote expeditious pre-radiation dental care.
Strategic alignment of clinical trials at the National Cancer Institute Center for Cancer Research: Development of the clinical mission and baseline portfolio metrics.
Authors: D. M. Dilts, S. K. Cheng, R. H. Wiltrout, W. L. Dahut, M. Bronez, L. J. Helman
Journal: Journal of Clinical Oncology (2011)

e16619 Background: The NCI – Center for Cancer Research (CCR) plays a unique role in the advancement of oncology research. The strategic alignment of clinical research to the CCR mission is critical as many CCR clinical trials (CTs) require support from centralized resources. A clinical mission was developed, linked to strategic dimensions, and evaluated using existing and proposed CTs. Methods: In a 2-year development cycle, a CCR clinical strategic mission was derived from input of the CCR community, leadership, and NCI overall. This mission fostered 3 streams of inquiry: identifying strategic dimensions, capturing metrics, and developing processes for shared resource requests. For retrospective analysis (RA), all CTs closed to accrual between 1/2006–12/2009 were evaluated with respect to publications and if the publications were published in high impact journals (i.e., top 10 in impact factor journal with “Medicine, General” and “Oncology”). For prospective analysis (PA), proposed CT from all branches were evaluated. Results: The clinical mission linked to 4 strategic dimensions. To evaluate 1 performance metric of these dimensions, a RA of the completed CT showed 53.3% (n=64) trials with at least one publication, which compares favorably with the average of 27.3% of NIH funded trials published (Ramsey & Scoggins 2008). Of these papers, 46.9% (n=30) were in high-impact journals. PA of incoming CTs identified 66% (25 of 38) as high impact CTs. A Strategic Alignment and Resource Checklist was developed to prospectively evaluate strategic importance of incoming CTs, to identify needed shared resources, and to optimize resource allocation decisions. Conclusions: It is possible to align CTs to an overall strategic clinical mission, to retrospectively and prospectively measure the portfolio of CTs against the mission, and to aid PIs in understanding how a CT relates to the mission and resource allocation decisions. While every organization is unique with regard to mandate, strategy, and capabilities, the process to develop a focused approach to implementing an overall clinical mission are similar. Ongoing research will evaluate the long-term success of these efforts.
A phase I study with tumor molecular pharmacodynamic (MPD) evaluation of dose and schedule of the oral mTOR-inhibitor Everolimus (RAD001) in patients (pts) with advanced solid tumors
Authors: J. Tabernero, F. Rojo, H. Burris, E. Casado, T. Macarulla, S. Jones, S. Dimitrijevic, K. Hazell, N. Shand, J. Baselga
Journal: Journal of Clinical Oncology (2005)

3007 Background: Everolimus (E), an oral derivative of rapamycin, inhibits mTOR, a protein kinase downstream of PI3K and Akt, involved in the regulation of cell growth, proliferation and survival. In preclinical models, the administration of E is associated with reduction of mTOR downstream phosphorylated(p)-S6 (p-S6) and p-4E-BP1, and occasionally with increase in upstream p-Akt. This study explores safety, PK and MPD changes in tumor at different doses and schedules of E to define the recommended dose for further development. Methods: Pts with advanced solid tumors were treated in successive cohorts of E: weekly 20, 50 and 70 mg or daily 5 and 10 mg. Dose escalation depended on dose limiting toxicity (DLT) rate during the first 4-week period. Pre- and on-treatment steady-state (24hr post-dose and, for the weekly schedule, 5 days post-dose) tumor biopsies were obtained from each pt. Tumor tissue was evaluated by immunohistochemistry (IHC) for p-S6, p-4E-BP1 and p-Akt expression by a pathologist blinded for the biopsy sequence. Results: 33 pts have been treated with 6–8 pts in each cohort. Grade 3 DLT occurred in 5 pts comprising stomatitis (1 pt at 10 mg daily, 2 at 70 mg weekly), neutropenia and hyperglycemia (1 pt each at 70 mg weekly). There were one partial response (colon cancer) and 2 stabilizations of >4 months (renal cell and breast cancer). MPD studies (see table) demonstrated an almost complete inhibition of p-S6 at all doses and schedules (p=0.001). Preliminary results suggest a dose-related decrease in p-4E-BP1 and increase in p-Akt expression with maximal effect at 10 mg daily and ≥50 mg weekly. Conclusions: This phase I study shows that E, at the doses and schedules studied, results in intratumoral inhibition of mTOR signaling. Based on the toxicity profile and the MPD findings, a dosage of 10 mg daily can be recommended for further phase II-III development with E as a single agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Merck KGaA, Novartis, Roche, sanofi-aventis Novartis
Adjuvant chemotherapy after trimodality therapy in locally advanced esophageal cancer.
Authors: Divya Yerramilli, Davendra Sohal, Ursina R. Teitelbaum, Paul Stephen Wissel, Nevena Damjanov, Bruce J. Giantonio, Peter J. O'Dwyer, John Peter Plastaras, Edgar Ben-Josef, James M. Metz, John Kucharczuk, Noel Williams, Smith Apisarnthanarax
Journal: Journal of Clinical Oncology (2014)

144 Background: The benefit of adjuvant chemotherapy after preoperative chemoradiation and surgery is unclear in patients with locally advanced esophageal cancer. We studied the toxicities and clinical outcomes in patients treated with or without adjuvant chemotherapy (CTX) after trimodality therapy. Methods: Records of patients with T3+ or N+ esophageal cancer who received preoperative chemoradiation followed by surgical resection from 2003-2013 were reviewed. Patients with postoperative deaths or poor performance status within 3 months after surgery were excluded (n = 13). Tolerability and hematologic toxicities of adjuvant CTX were recorded. Clinical outcomes of patients treated with adjuvant CTX were compared with a cohort of patients who received no further therapy (NFT). Results: Of the 81 trimodality patients included in the study, 53 received CTX and 28 received NFT after surgery. Median follow-up time was 23 months. FOLFOX (34%), cisplatin/5-FU (15%), 5-FU/LV (15%), ECF (13%), and carboplatin/paclitaxel (9%) were the most commonly used adjuvant regimens. Multiple rationales for adjuvant CTX were cited, including pathologic nodal status (32%), favorable pathologic response (61%), and provider preference (51%). Grade III/IV hematologic toxicity occurred in 11% of the CTX group: leukopenia (8%/2%), neutropenia (4%/4%), and thrombocytopenia (2%/0%). Two patients in the CTX group did not complete their prescribed CTX, which was discontinued after 1 cycle. Patient and clinical characteristics between CTX and NFT patients were well-balanced, except for pathologic complete response (pCR) rates (CTX 25% vs. NFT 50%, p=0.03). Three-year OS and DFS were similar between CTX and NFT patients (74% vs 70%, 60% vs. 64%, respectively). In patients who achieved pCR (33% overall), adjuvant CTX was associated with an improved 3-yr OS (86% vs. 62%), but the difference did not reach statistical significance (p=0.22). Distant failures occurred in 11% of the CTX group and 18% of the NFT group. Conclusions: Adjuvant CTX after trimodality therapy in esophageal cancer is feasible and well-tolerated with encouraging clinical outcomes. Further studies are needed to define the role of adjuvant CTX in these patients.