tbuckley/cabot-search huggingface dataset:
Low-dose temozolomide modulation of peripheral blood regulatory T cells before dendritic cell-based vaccination in metastatic melanoma: Phase I/II study.
Authors: L. Ridolfi, L. Fiammenghi, M. Petrini, A. Granato, V. Ancarani, E. Pancisi, M. Guidoboni, A. Riccobon, P. A. Ascierto, R. Ridolfi
Journal: Journal of Clinical Oncology (2010)

TPS311 Background: Dendritic cells (DCs) play a central role in the induction of specific antigen recognition and tumor cell killing. Therapeutic vaccination with DCs is based on the potential for the in vitro cultivation and maturation of DC precursors from peripheral blood over a maximum of 7 days using GM-CSF and IL-4 in order to avoid the influence of immunosuppressive mechanisms present in tumor tissue. Among these, attention has recently focused on CD4+CD25+FoxP3+ T lymphocytes (T-regs). It has been seen that daily low-dose temozolomide (TMZ) induces lymphopenia, with a consequent reduction in T-regs (Su YB, J Clin Oncol, 2004). Furthermore, in a preliminary experience, we evaluated the expression of tumor endothelial marker 8 (TEM8) as a predictive marker of immunological and clinical response in mature DCs (mDCs) (Venanzi FM, Cancer Immunol Immunother, 2009). Following our experience of a vaccination trial using autologous mDCs pulsed with autologous tumor lysate (ATL) and keyhole limpet hemocyanin (KLH) (Ridolfi R, J Transl Med, 2006), we activated a phase I/II study using low-dose TMZ before vaccination. The primary endpoints of the study are treatment feasibility and toxicity evaluation. Secondary endpoints are clinical response, T-reg modulation, overall survival, delayed type hypersensitivity (DTH) test as in vivo immunomonitoring, and TEM8 expression in mDCs. Methods: Patients with stage IV melanoma, without brain metastases but in progression after first- or second-line therapy, have been enrolled. The treatment schedule consists of TMZ 75 m2/day (maximum total dose 100 mg/day) given for 14 days before treatment, day 0 mDC vaccination, days 2-6 IL-2 3 MIU/day s.c. q 21 days, for 6 cycles, and only monthly vaccine thereafter. Blood samples for T-reg evaluation are taken on days 0 and 8 of the first and fifth cycle. DTH test for in vivo immunomonitoring is performed at baseline and every 4 vaccinations thereafter, as are clinical and radiological evaluations. TEM8 expression is evaluated in mature DCs at baseline. Fifteen patients have been enrolled and no major toxicities have been observed to date. No significant financial relationships to disclose.
Extranodal lymphoma presenting in distinctly unusual locations: A case series.
Authors: S. Arora, A. Neravetla, V. Kollu, S. Sirop, S. Nagpal
Journal: Journal of Clinical Oncology (2011)

e18560 Background: Non-Hodgkin lymphoma typically originate from lymph nodes. Extranodal presentations are seen in 20% of cases, most commonly from the stomach. We report three cases of primary extranodal lymphoma in distinctly unusual locations. Methods: Three patients presented with tumors where evaluation provided unexpected diagnoses of lymphoma; No other sites of involvement identified. Results: 77WF: presents with hoarseness of voice and left neck mass. Initial labs were unremarkable. Radiologic studies detected a 10cm. FDG-avid mass in thyroid gland. Core biopsy revealed diffuse large B-cell lymphoma (DLBCL). Within three days of R-CHOP chemotherapy, neck mass was undetectable. She continues to be in remission at 2 years via PET-CT. 32WF: presents with a 6-week history of pain and increasing girth. CT revealed a 13.5 cm pelvic mass for which she underwent TAH/BSO. Pathology revealed Burkitt lymphoma with t8;14. Post R-HyperCVAD chemotherapy PET scan was negative for FDG-uptake. Patient eventually succumbed to neutropenic sepsis. 80WF: presents with mild epigastric pain of four weeks. Imaging noted a FDG-avid 5.6 cm mass of the pancreas with vascular entrapment. Initial biopsy done at local community hospital was negative. EUS-guided biopsy performed at university center was reported as adenocarcinoma, which did not fit with her clinical picture and normal CA 19-9 level; diagnosis was challenged by oncologist. Repeat percutaneous core biopsy showed CD20+ DLBCL. She was treated with RT-CHOP and remains disease free two years after therapy. Conclusions: Primary extranodal NHL is rare and may mimic anaplastic thyroid carcinoma, ovarian carcinoma and pancreatic adenocarcinoma. Lack of native lymphoid tissue makes primary lymphoma of thyroid a rare entity (<1% of NHL). NHL involves the ovaries in 18% of cases, however it is the primary site in <0.5%. Primary pancreatic lymphoma comprises 0.2% of all pancreatic malignancies and <0.5% of NHL; complete remission can be achieved with chemotherapy alone. Management and prognosis are drastically altered with accurate pathological diagnosis. Lymphoma must be considered in the differential diagnosis as systemic therapy can yield complete remission, obviating the need for surgery.
Meeting patient and provider eTechnology needs: A provincial approach.
Authors: Erin Redwood, Richard Smith, Chanson Robert Garay, Rebecca Truscott, Shama Umar, Melissa Kaan, Nancy Kraetschmer, Gemma Lee, Vishal Kukreti
Journal: Journal of Clinical Oncology (2016)

153 Background: Cancer Care Ontario is the government agency responsible for improving cancer services across Ontario, and for implementing standards such as quality care, benchmarking and system navigation. In this role, a provincial information management and information technology (IM/IT) strategy across the patient continuum of care is essential to achieve the goal of improving the performance of the healthcare system and enhancing quality of care. Methods: Cancer Care Ontario developed a standardized approach for an IM/IT strategy through clinical engagement, needs assessment, gap analysis, clinical standardization influencing product build, usability testing, change management and post-implementation evaluation. Results: See table below. Conclusions: Ontario’s strategy for IM/IT initiatives includes a repertoire of eTools for system, patient and clinician level end user needs. An ongoing evaluation strategy including real-time patient experience measures will further strengthen the approach. [Table: see text]
Prognostic value of angiogenesis in patients following curative resection of gastric cancer (GC)
Authors: O. Vidal, J. P. Metges, A. Soriano-Izquierdo, A. Palacín, I. Elizalde, A. Castells, C. Fondevila, M. Robaszkiewiecz, A. Volant, M. Pera
Journal: Journal of Clinical Oncology (2005)

9605 Background: Despite novel therapies in GC, long-term prognosis remains poor. Assessment of angiogenesis holds the promise of predicting outcome in an individual basis, as well as to identify novel therapeutic targets. This study was aimed at evaluating the prognostic significance of tumor angiogenesis assessed by the expression of angiogenic factors and proteases in patients undergoing curative (R0) GC resection. Methods: In 148 patients with R0 GC, tumor microvessel density and expression of VEGF, angiopoietin-2 (Ang2), cyclooxigenase-2 (COX2), p53, urokinase-type plasminogen activator and its inhibitor (PAI1), and matrix metalloproteinases (MMP)1 and 9 were assayed by immunohistochemistry. We also evaluated 12 clinico-pathological variables: age, sex, pTNM, degree of differentiation, Lauren’s classification, vascular, lymphatic and perineural invasion, lymph node ratio, type of surgery, extent of lymphadenectomy and adjuvant chemotherapy. Univariate and multivariate analyses were performed to select the independent prognostic factors, and to adjust results of the molecular study for any significant clinical variables. Results: After a mean follow-up of 56±4 months, the probability of overall survival at 2, 5, and 10 yrs was 66%, 49% and 31%, respectively. The univariate analysis identified VEGF (p=0.002), Ang2 (p=0.001), COX2 (p=0.04), PAI1 (p=0.0002), and MMP9 expression (p=0.01), along with pTMN, Lauren’s classification, lymphatic invasion, lymph node ratio, and extent of lymphadenectomy as variables associated with overall survival. The mean disease-free survival was 52±4 months, the probability of tumor recurrence being 67%, 51% and 45% at 2, 5 and 10 yrs, respectively. Predictive variables for recurrence were the same as those identified for overall survival. Furthermore, multivariate analysis identified VEGF, Ang2 and PAI1 as independent predictive factors, but adjusting for significant clinical variables, only VEGF expression maintained its independent prognostic value. Conclusions: After a long follow-up period, VEGF expression predicts both overall survival and tumor recurrence in patients with R0 GC. VEGF might be a tempting therapeutic target in GC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration La Caixa
Oral clodronate maintains bone mass in women with primary breast cancer
Authors: E. McCloskey, A. H. G. Paterson, T. J. Powles
Journal: Journal of Clinical Oncology (2005)

535 Background: Breast cancer treatments commonly suppress oestrogen levels, accelerate bone loss and increase osteoporosis risk. As hormone replacement is contraindicated, bisphosphonates provide useful alternatives. Oral clodronate (Bonefos) 1600mg reduced the incidence of skeletal metastases and improved overall survival in a double-blind placebo-controlled study of 1069 women with primary breast cancer. We compared the effects of clodronate on spine and hip bone mineral density (BMD) during treatment and over a further 3-year follow-up period. Methods: BMD was measured by dual x-ray absorptiometry (Hologic QDR1000, Bedford, MA) in 498 women at first diagnosis of breast cancer (n=243 and 255 for clodronate and placebo respectively). The effects were estimated by computing annual rates of change in BMD. Results: Over 2 years of treatment, clodronate significantly increased the mean BMD at the spine and total hip while patients in the placebo group demonstrated a significant decrease at both sites (mean between group differences of +0.016, 95%CI 0.010–0.021g/cm2, p<0.0001 for spine and +0.006, 95%CI 0.002–0.010g/cm2, p=0.004 for total hip BMD). During the 3 years of follow-up off treatment, a statistically significant but similar decrease in BMD was observed for both clodronate and placebo groups at all sites. The mean between group difference for annual change in spine BMD was −0.001g/cm2 (95%CI −0.004–0.001, p=0.22) while that for the total hip was 0g/cm2 (95%CI −0.002 −0.002). There were no cases of osteonecrosis. Conclusions: During 2 years of treatment, oral clodronate 1600mg daily has a protective effect on spine and hip bone mass as judged by effects on BMD. After discontinuation, rates of bone loss are similar to, but not greater than, those in placebo-treated women so that at 5 years women previously treated with clodronate still have significantly higher BMD. There may be increased benefit from a longer treatment with clodronate. The optimum duration of treatment with clodronate to protect the skeleton and reduce skeletal metastases remains to be determined. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Berlex/Schering AG, Eli Lilly, Pfizer, Roche AstraZeneca, Berlex/Schering AG, Eli Lilly, Pfizer, Roche, Schering AG Schering AG
Comparison of efficacy and tolerance of first-line palliative chemotherapy EOX and mDCF regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors.
Authors: Sebastian Ochenduszko, Kamil Konopka, Miroslawa Puskulluoglu, Katarzyna Urbanczyk, Andrzej Budzynski, Maciej Matlok, Agata Lazar, Anna Sinczak-Kuta, Krzysztof Krzemieniecki
Journal: Journal of Clinical Oncology (2015)

135 Background: The aim of the study was to compare efficacy and tolerance of first-line palliative chemotherapy EOX (epirubicin/oxaliplatin/capecitabine) and mDCF (docetaxel/cisplatin/5FU/leucovorin) regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors. Methods: Each chemotherapy regimen was assigned with 21 patients. Planned treatment consisted of 12 every-two-weeks mDCF cycles (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or 8 every-three-weeks EOX cycles (epirubicin 50mg/m2 day 1, oxaliplatin 130mg/m2 day 1, capecitabine 1250mg/m2/d days 1 to 21). The primary endpoint was overall survival in all patients who commenced at least one chemotherapy cycle. Results: Median progression-free survival was 5.8 months in EOX group and 7.5 months in mDCF group (p=0.11), and median overall survival was 8.5 months and 12.0 months respectively (p=0.219). Due to toxicity, patients in the EOX arm had more frequent reductions of cytostatics doses (42.9% vs 5.0%; p=0.009) as well as delays in the administration of subsequent chemotherapy cycles (81.0% vs 65.0%; p=0.424). Rates of all grade 3 or 4 adverse events were comparable between both arms (76.19% in the EOX vs 70.0% in the mDCF; p=1.000). Toxicities that occurred more frequently in the EOX group compared to mDCF group were: nausea (28.6% vs 5.0%; p=0.093), thromboembolic events (19.0% vs 10%; p=0.663) and grade 3 or 4 neutropenia (71.4% vs 55.0%; p=0.443). Conclusions: In this patients population with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors treatment with mDCF regimen was associated with a statistically non-significant 3.5 month longer median overall survival without increase in toxicity. Updated data will be presented.
Current management and proposal for guidance of radiation cystitis (RC): Results of a British Uro-oncology Group (BUG) survey.
Authors: Amit K. Bahl, Robert Anthony Huddart, Heather Payne
Journal: Journal of Clinical Oncology (2013)

297 Background: Although RC is a potentially significant acute and/or chronic complication of radiotherapy to the pelvic area (15-20% incidence), there is limited information about how it is managed in practice. Methods: The BUG membership (comprising of consultant Uro-oncologists) was surveyed as to their perception on and management of RC. Results: 87% (45/52) of respondents supervise radiotherapy to the bladder/pelvis. Of these 45, most consider acute RC during or immediately after treatment a significant problem in ‘some' (56%) or the ‘majority' (11%) of cases (‘minority': 33%). Late RC was mostly considered a significant problem in the ‘minority' of cases (73%), with the rest feeling it was a significant problem in ‘some' cases (27%). During radiotherapy or at follow-up the majority ‘always' (22%) or ‘sometimes' (60%) record the grade of cystitis (‘never': 18%). 93% do not have local guidelines for managing RC. The treatments most frequently used to treat acute RC are: fluids (71%); cranberry juice (36%); analgesia (36%); non-steroidal anti-inflammatory drugs (NSAIDs; 29%); and anti-spasmodics (18%). Mild late RC is treated similarly (fluids: 29%; analgesia: 22%; cranberry juice: 18%; NSAIDs: 16%), although 20% might consider no treatment. For moderate/severe late RC, most refer to an urologist (64%), with grade ≥2 cases, those with haemorrhagic cystitis (20%), and symptoms &gt;90 days post-radiotherapy (18%) being the most common reasons for referral. For those treating moderate/severe late RC, hyperbaric oxygen (38%), fluids (19%), and analgesia (19%) are most commonly used. Over half were not aware of alternative treatment options including mesna (69% not aware), sodium hyaluronate (62%), intravesical prostaglandin E1/E2 (62%), sodium pentosanpolysulphate (60%), or intravesical formalin (51%). All supported the development of national guidelines in collaboration with the British Association of Urological Surgeons and British Association of Urology Nurses. Conclusions: RC is acknowledged as a potentially significant issue, and, with the majority of cases managed by oncology, there is a recognised need for further guidance on optimal treatment and BUG has started this work.
miR-17-3p Contributes to Exercise-Induced Cardiac Growth and Protects against Myocardial Ischemia-Reperfusion Injury
Authors: Jing Shi, Yihua Bei, Xiangqing Kong, Xiaojun Liu, Zhiyong Lei, Tianzhao Xu, Hui Wang, Qinkao Xuan, Ping Chen, Jiahong Xu, Lin Che, Hui Liu, Jiuchang Zhong, Joost PG Sluijter, Xinli Li, Anthony Rosenzweig, Junjie Xiao
Journal: Theranostics (2017)

Limited microRNAs (miRNAs, miRs) have been reported to be necessary for exercise-induced cardiac growth and essential for protection against pathological cardiac remodeling.Here we determined members of the miR-17-92 cluster and their passenger miRNAs expressions in two distinct murine exercise models and found that miR-17-3p was increased in both.miR-17-3p promoted cardiomyocyte hypertrophy, proliferation, and survival.TIMP-3 was identified as a direct target gene of miR-17-3p whereas PTEN was indirectly inhibited by miR-17-3p.Inhibition of miR-17-3p in vivo attenuated exercise-induced cardiac growth including cardiomyocyte hypertrophy and expression of markers of myocyte proliferation.Importantly, mice injected with miR-17-3p agomir were protected from adverse remodeling after cardiac ischemia/reperfusion injury.Collectively, these data suggest that miR-17-3p contributes to exercise-induced cardiac growth and protects against adverse ventricular remodeling.miR-17-3p may represent a novel therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.
Nomogram including pretherapeutic parameters for prediction of early response after neoadjuvant treatment in rectal cancer: Results from a prospective randomized study.
Authors: Jianwei Zhang, Yue Cai, Huabin Hu, Ping Lan, Lei Wang, Meijin Huang, Liang Kang, Xiaojian Wu, Jiayu Ling, Jian Xiao, Jianping Wang, Yanhong Deng
Journal: Journal of Clinical Oncology (2016)

716 Background: To establish a clinical nomogram with pretherapeutic parameters for predicting pathologic complete response (pCR) and tumor downstaging after neoadjuvant treatment in patients with rectal cancer. Methods: From Jan 2011 to Feb 2015, complete data was available for 309 patients with rectal cancer who received concurrent chemoradiotherapy or chemotherapy alone enrolled in FOWARC study. All pre-treatment clinical parameters were collected to build a nomogram for pCR and tumor down-staging. The model was subjected to bootstrap internal validation. The predictive performance of the model was assessed with concordance index (c-index) and calibration. Results: Of the 309 patients, 55 (17.8%) had achieved pCR, 138 (44.7%) patients were classified as good down-staging with ypTNM stage 0-I. Basing on the multivariate logistic regression and clinical consideration, 5 factors were identified to be the independent predictors for pCR and good downstaging, respectively (Table 1). The predictive nomograms were developed (fig 1 and 2) to predict the probability of pCR and good down-staging with a C-index of 0.802 (95% CI: 0.736-0.867) and 0.73 (95% CI: 0.672-0.784). Calibration plots showed good performance on internal validation. Conclusions: The nomograms provide individual prediction of response to different preoperative treatment for patients with rectal cancer. This model may help physician in patient selection for optimized treatment. Further external validation is warranted. [Table: see text]
Preliminary cost-consequence analysis of the INTEREST trial, a randomized trial of docetaxel versus gefitinib as 2<sup>nd</sup> line therapy in advanced non-small cell lung cancer
Authors: A. M. Horgan, F. A. Shepherd, P. A. Bradbury, R. Ng, N. B. Leighl
Journal: Journal of Clinical Oncology (2008)

8110 Background: The INTEREST trial is the first to demonstrate non-inferiority of EGFR TKI gefitinib compared to standard second-line chemotherapy (docetaxel) in NSCLC,with better quality of life in gefitinib-treated patients. Methods: A cost-consequence analysis of direct medical costs was undertaken, given non-inferiority of the two study arms, from the perspective of the Canadian public health system. Direct medical costs (2007 CAD$)were applied to resources (e.g study treatment, toxicity management) obtained from INTEREST trial data in the public domain. Mean overall cost per patient on each treatment arm was calculated from the start of treatment until first progression. Incremental costs over best supportive care (BSC), based on an analysis of the TAX317 trial, are also calculated. Results: The mean total cost per patient treated with gefitinib was $10,840 and $8,613 for docetaxel, resulting in an incremental cost of gefitinib treatment over docetaxel of $2,227. Drug costs are the major driver, $10,515 for gefitinib (6.5 cycles) versus $6,942 for docetaxel (4.4 cycles). Limited data on toxicity management, (e.g. febrile neutropenia, anemia, rash), are available, and cost estimates are $325 for gefitinib and $1,671 for docetaxel-treated patients. Additional hospitalization data were not available and therefore not included in these estimates. Based on published cost data for BSC, the incremental cost of gefitinib over BSC is estimated at $12,916 with available data, with an incremental cost effectiveness ratio of $37,988/life-year gained. Conclusion: Gefitinib second-line has similar efficacy compared to docetaxel with better quality of life. While drug costs for gefitinib are greater, costs for toxicity management are substantially less, and underestimated in this analysis. Gefitinib second-line is an attractive and affordable alternative for patients with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, sanofi-aventis