tbuckley/cabot-search huggingface dataset:
A phase II trial using altered fractionation irradiation with concomitant chemotherapy in the management of patients with muscle invasive bladder cancer (MIBC)
Authors: E. El Nashar, E. El Nashar, S. El Noweim, S. Abdel Moneim, Y. Rostom
Journal: Journal of Clinical Oncology (2005)

4532 Background: To identify the place of conservative treatment in patients (pts) with MIBC using concomitant cisplatin (C) and gemcitabine (G) with bifractionated split course radiotherapy. Methods: Eligible pts with stages T2-T4a, N0 M0 were entered in this study. Treatment began with transurethral resection (TUR) with complete macroscopic debulking followed by induction chemoradiation. The treatment regimen consisted of C 15 mg/m2 and G 200 mg/m2 on days 1–3 and 15–17 (one cycle of 6 days induction chemotherapy). On days 1, 3, 15, and 17, radiation was given immediately following chemotherapy using twice-daily 2 Gy per fraction to the whole pelvis for a total dose of 16 Gy delivered in 8 fractions over 17 days. Patients with a complete response (CR) via cystoscopy after the induction cycle received another chemoradiation cycle as consolidation. Patients who did not achieve CR underwent cystectomy. Both groups received outpatient adjuvant chemotherapy: G 1000mg/m2 on days 1, 8, and 15 plus C 70 mg/m2 on day 1 every 28 days for 6 cycles. Results: From July 2001 to January 2003, 36 pts were enrolled. All pts were evaluable for efficacy and toxicity. Twenty pts (55.6%) achieved CR after induction therapy and received consolidation chemoradiation. Of the pts who still had detectable tumor, 9 pts (25.0%) underwent radical cystectomy and 7 (19.4%) refused cystectomy and received the same chemoradiation. 6/16 died of progressive disease. The median follow-up is 22 months. The 2-year overall survival is 80%, and the 2-year probability of surviving with an intact bladder is 69.4%. Grade 3/4 thrombocytopenia was observed in 8 pts (22.2%), non hematologic toxicities in the form of grade 3 radiation cystitis in 3 pts (8.3%) and proctatitis in 4 pts (11.1%). Conclusions: This trial comprising of local TUR plus concurrent C/G, and hypofractionated radiation has been associated with acceptable hematologic toxicity. Both the complete response rate to induction therapy and the 2-year survival rate with an intact bladder are encouraging. Longer follow-up is needed to assess efficacy. No significant financial relationships to disclose.
Long-term results of a prospective trial of preoperative radiation and postoperative brachytherapy for retroperitoneal sarcoma
Authors: L. A. Mikula, M. A. Ko, C. N. Catton, J. J. Jones, B. O’Sullivan, J. Couture, C. J. Swallow
Journal: Journal of Clinical Oncology (2005)

9007 Background: Recent single-institution series report a 5-year survival of approximately 50% after resection alone for retroperitoneal sarcoma (RPS). We evaluated the effects of preoperative external-beam radiation (XRT) and postoperative brachytherapy (BT) in a prospective trial for patients with resectable RPS. Methods: Between June 1996 and November 2002, 54 patients completed preop XRT and underwent total gross resection. Initially, all patients were treated with BT in the early postoperative period. When we found that BT to the upper abdomen was associated with a high rate of morbidity, the protocol was modified and BT was used only selectively in the lower abdomen. Survival curves were generated using the Kaplan-Meier method, and compared using Cox proportional hazards. Statistical significance was set at p≤0.05. Minimum follow-up was 24 mo, and median follow-up was 47 mo. Results: In the total group of 54 patients, 31 were female, median age was 58 yr (38–79), and median tumor size was 19 cm (3–40). 76% presented with primary RPS and 24% with recurrent disease. 44% had low grade tumors and 56% high grade. Preoperative XRT was well-tolerated, with RTOG scores ≤2 in all patients. 5 yr. overall survival (OS) was 75% (95% CI, 69–81%). 16 patients relapsed during the follow-up interval, but 5 of these were re-resected and rendered disease-free (DF). 5 yr DFS was 71% (64–78%). Grade was the only significant predictor of OS and DFS. There was no difference in age, gender, tumor size, presentation or grade between the patients who received BT (n=19) and those who did not (n=35). Of those treated with BT, 4 experienced life-threatening postoperative morbidity, and 6 significant chronic toxicity. BT was not associated with improved OS or DFS. Conclusions: In long-term follow-up, combined management of RPS with preoperative XRT and complete resection was associated with promising oncologic outcomes. These results highlight the importance of the current ACOSOG trial of preop XRT vs surgery alone. BT was associated with significant morbidity and did not confer any survival advantage. No significant financial relationships to disclose.
A phase II trial of gemcitabine plus capecitabine (GX) in patients with advanced renal cell cancer (mRCC) previously treated with immunotherapy
Authors: N. M. Tannir, E. Jonasch, C. McMichael, X. Wang, L. Wooten, C. S. Ng
Journal: Journal of Clinical Oncology (2005)

4598 Background: There is no standard therapy for pts with mRCC who develop progressive disease (PD) after immunotherapy. Novel molecular targeting agents are showing promising results but their full impact is still evolving. A phase II study of GX by CALGB produced modest activity and toxicity greater than expected. (WM Stadler et al, Abstract 4515 ASCO proceedings 2004) Methods: 81 pts (63 males, 18 females) with previously treated mRCC received GX as follows: G 1000 mg/m2 IV on days 1, 8, 15; X 830 mg/m2 po bid x 21 days; cycles repeated q 28 days. Cycles were interrupted for dose-limiting toxicity with dose reductions applied for subsequent cycles. The primary endpoint of the study is progression-free survival (PFS). Secondary endpoints are response rate (RR), overall survival (OS) and toxicity. Results: 81 pts are evaluable for toxicity and 75 pts are evaluable for response. Median age is 61 yrs (35–76). Performance score (PS) 0 (14 pts), PS 1 (54 pts), PS 2 (13 pts). Number of prior therapies: 1 (55 pts), 2 (18 pts), 3 (3 pts). Prior therapy: high-dose IL-2 (13 pts); the rest had IFN +/- IL-2 +/- experimental agents. Number of metastatic sites: 1 (15 pts), 66 pts had ≥ 2. There are 7 partial responses (10%). Median PFS is 4.9 mos (95% CI 3.5–9.4). Median OS has not been reached yet (14+ mos). 14 pts have died of PD. 61 pts had interruption of therapy and dose reduction at least once. Of 371 cycles delivered, toxicities observed include grade 3/4 neutropenia (17.7%), grade 2–4 thrombocytopenia (6.7%), grade 2/3 anemia (2.2%), grade 2/3 hand-foot syndrome (8.6%), grade 2/3 mucositis (4.3%), grade 2/3 nausea/vomiting (2.7%), grade 2/3 diarrhea (2.2%), grade 2/3 infections (1.9%). 10 pts had grade 2/3 fatigue, 1 pt had grade 4 fatigue, 7 pts had deep vein thrombosis, 2 pts had pulmonary embolism, 2 pts had hematuria. There were no therapy-related deaths. Conclusions: GX has modest activity in mRCC and could be used in combination with targeted therapy, but the dose/schedule used in this study have to be modified. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Merck, Pfizer Celgene, Eli Lilly, Novartis
Development and implementation of effective quality (Q) guidelines (G) in community (com) cancer centers (CC): The cancer quality program (CQP)
Authors: L. D. Bosserman, C. A. Presant, M. J. Vakil, R. C. Horns, G. Upadhyaya, B. Ebrahimi, C. L. Martel, C. H. Yeon, T. Young, M. D. Scalia
Journal: Journal of Clinical Oncology (2005)

6105 Background: National panels, institutes, and media have accused oncology of poor Q in patient (pt) care. In order to improve Q in com pt care, we developed the CQP. Methods: 8 oncologists and 3 nurse practitioners from 6 C com centers met every 2 wk over 1 year and selected process QG for 6 cancer sites across 4 areas from G in NCCN, NOA, and ASCO. The target areas were staging (S), treatment (T), pt education (E), and symptom management (SM). QG were formulated to be testable with electronic medical records (EMR). To test the QG, a pilot cohort of 50,000 covered lives in 1 CC were reviewed for compliance with QG. Results: AJCC S QG of 100% was met in 525 cancer pts. A subset of chemotherapy (CT) QG tested on 40 colon pts showed 100% compliance with offering adjuvant CT in stage 3 with 2/14 refusing. High compliance rates were due to the process of developing and implementing the QG, and the required data entry fields in the EMR. Other T QG not tested in the pilot were BREAST: all Stage 1, 2, 3 ER + or PR+ offered tamoxifen or AI, all stage 2,3 offered CT and received 85% of planned dose on time (pdot); OVARY: all stage 2,3,4 pt offered ct, all ct pt received 85% pdot: LYMPHOMA: all intermediate grade pt offered ct, all ct pt received 6–8 cycles with 85% pdot. Other T QG will be presented for NSCLC, PROSTATE, and COLORECTAL C. QG in E were all pt received summary of T at end of ct; and all pt received written plan for surveillance for recurrence, screening and C prevention. QG in SM were all pt received evaluation for pain, nausea, fatigue, neuropathy and depression; and all pt offered management if symptoms were present. The complete QG set was then evaluated with a test cohort of 100,000 covered capitated lives. Results of the test group will be presented and compared to the pilot results above. Conclusions: We have demonstrated a methodology for development and implementation of QG in com C centers. Use of CQP can give individual C centers a benchmark for demonstrating quality care delivery even in busy com CC which encourages improved compliance and performance. No significant financial relationships to disclose.
Abstract 19831: In Vivo Molecular Imaging of Human Pluripotent Stem Cell-derived Cardiomyocytes in a Murine Myocardial Injury Model via a Safe Harbor Integration of a Reporter Gene
Authors: Eric Rulifson, Yuka Matsuura, Miyuki Ariyama, Mouer Wang, Rahul Thakker, Atsushi Tachibana, Joseph Wu, Phillip Yang
Journal: Circulation (2014)

Background: Clinical application of pluripotent stem cells and their tissue specific derivatives will require in vivo monitoring of engraftment and systemic distribution following transplantation. Clinical translation of molecular imaging, employing reporter gene (RG) technology, requires site-specific transgene insertion at safe harbor loci, such as AAVS1. Hypothesis: Zinc finger nuclease (ZFN)-mediated integration of a RG into the AAVS1 locus in human embryonic and induced pluripotent stem cells (hESCs and iPSCs) will allow monitoring of pluripotent stem cell-derived cardiomyocytes (hCMs and iCMs) in host myocardium. Methods and Results: ZFN technology was used to integrate a triple fusion RG, containing firefly luciferase (BLI), red fluorescent protein (RFP) and herpes simplex virus thymidine kinase (PET), under regulation of a constitutive ubiquitin promoter, into the AAVS1 locus of hESCs and iPSCs. hESCs and iPSCs monoclonal lines were then differentiated into hCMs and iCMs, respectively, under chemically defined conditions using CHIR and IWR small molecules to modulate Wnt pathway activity. Co-localization of cardiac phenotype and striated morphology was readily observed (Fig. A). Site-specific integration was confirmed by southern blot analysis. RG expression by BLI was maintained successfully over 3 months in vitro. The hCMs (n=6) and iCMs (n=1) were transplanted into murine myocardial injury model. Four weeks post-injury, LVEF was better preserved in all cell-treated vs. PBS-treated mice (26.50 ± 2.325 (N=6) vs. 15.40 ± 4.600 (N=3), p&lt;0.05). Robust in vivo expression of ZFN-edited BLI and PET signal of engraftment persisted for 4-weeks duration (Figs. B and C). Conclusion: This study demonstrates the successful use of ZFN-edited cells to confirm the engraftment of hCMs and iCMs. ZFN technology enables targeted site-specific insertion of RGs to allow clinical translation of molecular imaging in cell therapy.
Optimizing the Quality of Breast Cancer Biomarker Use at Duke Cancer Institute
Authors: Arif H. Kamal, Steve Power, Gloria Broadwater, Audrey R. Holland, Paul K. Marcom
Journal: Journal of the National Comprehensive Cancer Network (2014)

Advances in identifying biomarker profiles in patients with early-stage breast cancer have improved 5-year curative rates. Identification of the HER2 receptor provides valuable information that has been shown to extend survival in adjuvant and metastatic settings. Current clinical guidelines discuss when confirmatory testing may be inappropriate. Using a quality improvement approach, the team at Duke Cancer Institute determined HER2 ordering practices in a large academic cancer center. HER2 ordering using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) was abstracted from the charts of 314 patients with early-stage breast cancer. Qualitative responses to current clinical practices were obtained from clinicians. Of the patients included, duplicate IHC was performed for 36% and in triplicate for 6%; repeat testing resulted in clinically significant change in HER2 status for approximately 20%. Repeat biomarker testing on metastatic biopsy sites “all of the time” was favored by the surveyed physicians. FISH was ordered for each grade of IHC: 0+ (>20% of cases), 1+ (>20%), 2+ (99%), 3+ (54%). Most physicians “strongly” or “somewhat” favored solutions that integrate order sets and care pathways into the electronic medical record. This quality improvement project identified root causes and solutions to practice variance in breast cancer biomarker ordering and interpretation. Further investigations are planned to standardize best practices while appreciating the clinical challenges posed by discordant test results.
Serum Concentrations of γG, γA, and γM Immunoglobulins in Patients With Carcinoma, Melanoma, and Sarcoma
Authors: Norman R. Hughes
Journal: JNCI Journal of the National Cancer Institute (1971)

The concentrations of γG, γA, and γM immunoglobulins in sera from 256 normal controls were compared with those from 984 patients with cancer of nonhematopoietic tissues. Male patients with carcinoma of the skin and lung had significantly increased γG and γA concentrations. γA was significantly increased in patients with cancer of the mouth, gut, and uterus, the ratio of the γA concentration to that of γG being significantly increased. Serum γM concentrations were significantly increased in male patients with sarcoma and in female patients with melanoma. Patients with primary ovarian cancer had a significantly lower than normal γM concentration. Normal females had a significantly higher γM concentration than normal males. In both normal controls and cancer patients, males had significantly higher concentrations of γA than females.
Developing Global Norms for Sharing Data and Results during Public Health Emergencies
Authors: Kayvon Modjarrad, Vasee S. Moorthy, Piers Millett, Pierre-Stéphane Gsell, Cathy Roth, Marie-Paule Kieny
Journal: PLoS Medicine (2016)

Among the core functions of the World Health Organization (WHO) are to provide "leadership on matters critical to health" and to shape "the research agenda and stimulate the generation, translation, and dissemination of valuable knowledge" in the interest of global public health [1].These mandates have converged, of late, in the area of data sharing.In April 2015, the WHO adopted a position on the timely, public disclosure of clinical trial results [2], adding to other calls that nondisclosure of research data must no longer be tolerated.The global norm advocated by the WHO is to release key outcomes of all interventional clinical trials in an open-access, searchable database within 12 months of primary completion.The WHO has since called on sponsors, investigators, journals, and other bodies to do all in their power to implement this standard.Even as this position is becoming widely accepted, it has become Summary Points• Leading stakeholders from around the world convened at a WHO consultation in September 2015, where they affirmed that timely and transparent sharing of data and results during public health emergencies must become the global norm.
Matrix metalloproteinase-1 is differentially expressed in signet ring cell, and intestinal colorectal carcinomas histotypes
Authors: A. Calascibetta, V. Gebbia, D. Cabibi, A. Martorana, F. Aragona, L. Rausa, R. Sanguedolce
Journal: Journal of Clinical Oncology (2007)

14564 Background: Signet ring cell colorectal carcinoma ( SRCC) pure is an infrequent and highly malignant variant of colorectal cancer, while this histological component is present in 30% of all colorectal carcinomas. In our previous studies we compared the E- Cadherin, β- Catenin, Fibronectin, Ki 67 and Thymidylate Synthase (TS) expression of SRCC, the intestinal type of colorectal carcinoma (ICRC) to try to explain the pathogenesis, the aggressiveness and the low 5 Fluorouracil (5FU) responsiveness of these tumours. We found that all SRCCs had very low levels of all markers and were in the post- mitotic phase of the cell cycle. To understand their high metastatic capability we assessed the SRCC expression of Matrix Metallo Proteinase-1 (MMP1), a proteolytic enzyme, suspected to play an important role in the progression of various cancer and compared it to the ICRC one. Methods: We tested MMP1 expression immunohistochemically on formalin-fixed, paraffin-embedded samples of 32 SRCC and 70 ICRC. Differences in the distribution of the study variables, and associations between variables were assessed by means of the ? 2 test. Results: SRCC showed a high expression of MMP1 over all in the invasion front of the tumour and in the neoplastic embolus rather then the ICRC (p&lt;0.001). Conclusions: As MMPs seem to play important role in tumour invasion and metastasis, recently they have gained attention as targets for new anticancer therapy strategies. MMPs inhibitors have been shown to prevent tumour spread both in vitro and in vivo and to inhibit tumour angiogenesis and some of them are being developed for clinical use. In these study we demonstrated that SRCCs showed a different MMP1 expression pattern from the ICRC one, for this reason an anti-MMP therapy should be advisable in these patients, because of their bad prognosis. No significant financial relationships to disclose.
A multicenter phase II study of induction CT with FOLFOX-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC)
Authors: F. De Vita, M. Orditura, R. Innocente, L. Vecchione, C. Pinto, V. Chiarion Sileni, E. Martinelli, A. Ruol, G. Catalano, F. Ciardiello
Journal: Journal of Clinical Oncology (2009)

4546 Background: Preoperative CRT improves the survival of pts with EC when compared with surgery alone. Epidermal growth factor receptor (EGFR) is overexpressed in 30–90% of EC and is associated with poor prognosis, providing the rationale for using the anti-EGFR monoclonal antibody cetuximab (C). The purpose of the study was to investigate the efficacy, toxicity and feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC in a multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the esophagus; staged by EUS, CT and PET scan; age 18–70y; PS &lt;2; normal organ functions.All pts received induction treatment with C at a starting dose of 400 mg/m 2 and further weekly infusion at a maintenance dose of 250 mg/m 2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. Simons two stage design was used. Primary endpoint was histopathological response rate. Results: Up to December 2008, 40 pts, 30 men, were enrolled from 4 institutions; median age 59 y (35–70y); AC 12; SCC 28; stage II 15, stage III 25 pts. At this time 32/40 pts were evaluable. The most frequent grade 3/4 toxicity of chemoradiotherapy were skin (32%),neutropenia (29%) and esophagitis (9%); 10 pts had no resection (9 progressive disease,1 patient's refusal). Of 22 operated pts, 17 pts (77%) had RO-resection, 5 pts had palliative surgery.2 pts died due to complications after surgery (1 after &gt; 30 days). The pathological response rate was 68 %, with a complete histopathological remission recorded in 6 pts (27%);17 pts (53%) are still alive without residual or recurrent disease. Conclusions: The current findings suggest the feasibility of incorporating cetuximab into a preoperative regimen for LAEC pts and an encouraging antineoplastic activity with 68% histopathological responders. No significant financial relationships to disclose.
High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group
Authors: RA Brown, SN Wolff, JW Fay, L Pineiro, RH Jr Collins, JP Lynch, D Stevens, J Greer, RH Herzig, GP Herzig
Journal: Blood (1995)
Hepatitis B Virus Reactivation and Prophylaxis During Solid Tumor Chemotherapy
Authors: Sonali Paul, Akriti Saxena, Norma Terrin, Kathleen Viveiros, Ethan M. Balk, John B. Wong
Journal: Annals of Internal Medicine (2015)

Background: Solid tumor chemotherapy regimens pose a risk for hepatitis B virus (HBV) reactivation, but screening and antiviral prophylaxis remains controversial because of insufficient evidence. Purpose: To determine the risk for HBV reactivation with and without antiviral prophylaxis and the effectiveness of prophylaxis in adults with solid tumors and chronic or resolved HBV infection. Data Sources: MEDLINE through 1 July 2015 and Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus through 1 March 2015. Study Selection: 26 English-language observational studies and randomized, controlled trials in patients with chronic or resolved HBV receiving chemotherapy for solid tumors. Data Extraction: Study characteristics, quality, and risk of bias were assessed by 1 researcher and verified by another independent researcher. Data Synthesis: Random-effects model meta-analyses were used to estimate the risk and odds ratio (OR) of reactivation with versus without antiviral prophylaxis. Reactivation in chronic HBV without prophylaxis ranged from 4% to 68% (median, 25%) with substantial heterogeneity. Prophylaxis reduced the risk for HBV reactivation (OR, 0.12 [95% CI, 0.06 to 0.22]), HBV-related hepatitis (OR, 0.18 [CI, 0.10 to 0.32]), and chemotherapy interruption (OR, 0.10 [CI, 0.04 to 0.27]). In 3 studies of patients with resolved HBV infection, none received HBV prophylaxis and reactivation risk ranged from 0.3% to 9.0%. Limitations: Significant heterogeneity in underlying study populations and treatment regimens, incomplete baseline data, possibility of publication bias, and limited study quality. Most studies were observational and from Asia. Conclusion: In patients with chronic HBV receiving solid tumor chemotherapy, the risk for HBV reactivation is similar to the risk with other types of immunosuppressive therapy. Results support HBV screening and antiviral prophylaxis before initiation of chemotherapy for solid tumors. Primary Funding Source: National Center for Advancing Translational Sciences and National Institutes of Health.