tbuckley/cabot-search huggingface dataset:
Comparison of two different adjuvant treatment approaches for patients with locally advanced gastric cancer.
Authors: M. Ekenel, L. Ozer, C. Ordu, E. K. Saglam, A. Kizir, E. N. Oral, N. F. Aykan
Journal: Journal of Clinical Oncology (2011)

e14537 Background: Standard treatment of locally advanced gastric cancer (GC) has become chemoradiotherapy (CRT) after the results of Intergroup trial. However, there is no randomized trial comparing CRT to chemotherapy (CT) alone in patients (pts) with very high metastatic lymph node involvement. In this evaluation we used the old version of GC staging and defined the lymph node status as N3 if pts had 15 or more metastatic lymph nodes. The aim of this study is to compare the efficacy of adjuvant (adj) CT over CRT in pts who had T1-4, N3, M0 tumors. Methods: Between Jan. 2005 and Jul. 2009, charts of 74 pts who had an adj treatment for GC at Istanbul University were retrospectively reviewed. Fifty three pts had adj CT alone and 21 pts received adj CRT. Age, sex, type of gastric resection, histopathologic features of the tumor and type of adj treatments were noted in each group. Disease free survival (DFS) and overall survival (OS) were calculated in both CRT and CT groups. Results: The median age was 52 years (25-81) and median follow up was 12.8 months. Median OS was 20 months (mo) and DFS was 11 mo for all pts. Seventy-three percent of pts underwent R0 resection and 23% of pts had R1 resection. Mean resected lymph node number was 37 (16-81). Mean metastatic lymph node number was 23 (16-77). T2, T3 and T4 tumors were 3%, 86%, 11%, respectively. Ninety-two percent of pts had lymphatic invasion, 78% had vascular invasion and 82% had perineural invasion. Omental involvement was seen in 13.5% of pts. Twenty-one pts received standard CRT protocol. In CT alone group, 40.5% of pts had bolus 5FU/FA regimen and others received cisplatin and FU based regimens with or without epirubicin. There was no difference in age, sex, type of gastric resection, histopathologic features of the tumor between 2 groups. DFS in CT only and CRT groups were 9 mo and 11 mo, respectively (p=0.7). OS in CT only and CRT groups were 18 mo and 20 mo (p=0.9). In univariate analysis, only omental invasion had poor prognostic factor for OS. Conclusions: In this retrospective review, we could not find any difference in terms of DFS an OS between 2 different adj treatment approaches. A prospective randomized trial to find the best treatment strategy is urgently needed for this subgroup of pts.
Docetaxel (D) plus high-dose calcitriol versus D plus prednisone (P) for patients (Pts) with progressive castration-resistant prostate cancer (CRPC): Results from the phase III ASCENT2 trial.
Authors: H. I. Scher, K. N. Chi, R. De Wit, W. R. Berry, P. Albers, B. Henick, P. Venner, A. Heidenreich, L. Chu, G. Heller
Journal: Journal of Clinical Oncology (2010)

4509 Background: For Pts with progressive CRPC, a placebo-controlled phase II study suggested that combining docetaxel (D) with high-dose calcitriol (DN-101) may increase survival compared to D alone. A randomized, open-label phase III study was undertaken to compare the safety and efficacy of D plus DN-101 to D plus P. Methods: 953 men with CRPC were randomized to ASCENT arm (45 μ g DN-101, 36 mg/m2 D, and 24 mg dexamethasone (DEX) weekly for 3 out of every 4 weeks) or control arm (5 mg P twice a day, and 75 mg/m2 D and 24 mg DEX every 3 weeks). The primary endpoint was overall survival, assessed by the Kaplan-Meier method. Results: Baseline demographics were comparable between the groups. Median-follow-up for Pts alive was 11.7 months. At an interim analysis, more deaths were observed in the ASCENT arm, and the trial was halted early. Median duration of study treatment was 16.6 weeks for ASCENT subjects and 21.0 weeks for controls. The Table shows deaths at final analysis, 6 months after study termination. Median overall survival was 16.8 months (95% CI, 15.8–19.3) for ASCENT subjects and 19.9 months (95% CI, 18.6-22.7) for controls. In multivariate analysis adjusting for baseline variables, ASCENT was associated with shorter survival (HR=1.33; p=0.019). The proportions of Pts with adverse events (AEs) were similar, and consistent with the known side effects of D. Dose modification for D toxicity was more frequent in the ASCENT arm (229 ASCENT vs. 160 control subjects). Conclusions: ASCENT treatment was associated with significantly shorter survival than the control. This difference might be due to weekly D dosing in the ASCENT arm, which in the TAX 327 trial (NEJM 351:1502, 2004) appeared to be inferior to D every 3 weeks, as in the control arm of this study. Deaths in each study arm ASCENT n=477 Control n=476 Disease-specific 142 (29.8%) 108 (22.7%) Other cause 32 (6.7%) 30 (6.3%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novacea Novacea
<i>O</i>-glicosylation alterations of proteins in gastric carcinoma.
Authors: H. Santos Sousa, T. Bouca-Machado, E. Lima-da-Costa, J. Pinto-de-Sousa, C. Gomes, C. A. Reis, L. David, J. Costa-Maia
Journal: Journal of Clinical Oncology (2011)

62 Background: The expression of immature forms of carbohydrates could help to better understand the biological behavior of gastric cancer. Methods: From a universe of 50 patients with gastric or gastroesophageal junction carcinoma submitted to surgical treatment between January and October 2009, in our department, 36 out of 38 carcinomas ressected during this period, were selected for a tumor tissue immunohistochemical study of the simple mucin-type carbohydrate antigens (Tn, STn, T and ST) and the Lewis carbohydrate antigens (SLea and SLex). Several clinico-pathological parameters were evaluated according to the expression pattern of the antigens studied. Results: The ressected gastric carcinomas presented a high incidence of tissue expression of the simple mucin-type and the Lewis carbohydrate antigens, with all cases presenting expression of at least 2 of the antigens and two thirds the expression of 4 or 5. The correlation between the simple mucin-type carbohydrate antigens was high, just as the same as with the Lewis carbohydrate antigens. The analysis of the clinico-pathological profile of gastric carcinomas according to the expression of these antigens revealed the following associations: Tn with venous invasion and perineural invasion; STn with tumor location and macroscopic form; T with age, gender, tumor dimensions and location; ST with macroscopic form and WHO classification; SLea and SLex with the tumor dimensions. Staging of the tumors also revealed associations with the expressions of these antigens: Tn with serosal invasion, lymph node metastases and stage; STn with lymph node ratio; SLea with serosal invasion and lymph node metastases; SLex with depth wall invasion, lymph node metastases and stage. The antigens T e ST did not reveal differences in the expression pattern according to staging. Conclusions: O-glicosylation alterations of proteins are related with gastric carcinoma, not only their incidence is high but they can also be linked with various clinico-pathological characteristics. The knowledge obtained from this study might serve as a starting point for future investigations taking into account the identification of new biomarkers based on glicosylation alterations of proteins. No significant financial relationships to disclose.
A higher sport-related reinjury risk does not mean inadequate rehabilitation: the methodological challenge of choosing the correct comparison group
Authors: Ian Shrier, Meng Zhao, Alexandre Piché, Pavel Slavchev, Russell J Steele
Journal: British Journal of Sports Medicine (2017)

Previous injury is a well-established predictor of subsequent injury in sports medicine. Some have interpreted this to mean that either our current methods of rehabilitation are inadequate or there is some permanent damage to the tissue and 100% rehabilitation is not possible. In 2011, we illustrated that these analyses and interpretations failed to account for the fact that some athletes are more prone to get injured, either physiologically, or because of their role/type of play. We suggested that the appropriate analysis would simply require using statistical methods that measured how each individual athlete's risk changed from preinjury to postinjury.In this paper, we revisit our recommendation and illustrate that it too would be flawed if the risk of injury changed over time independent of an injury ever occurring. This might be expected if general fitness were to decline over the season, or if the style of play changed between early season games and postseason championship games. Acknowledging that risk may change regardless of whether an injury occurred or not leads to three different general definitions of 100% rehabilitation: (1) a return to the baseline state, (2) a return to the immediate preinjury state and (3) a return to the state that would have been present had the initial injury never occurred. We guide the reader on how to estimate the risks for each definition and the assumptions that must be acknowledged.
Improving venous thromboembolism (VTE) prophylaxis for hospitalized malignant hematology/bone marrow transplant (heme/BMT) patients.
Authors: Melisa L. Wong, John Dzundza, Archana Ajmera, Ashley Gustafson, Mimi Lo, Richard Fong, Larissa Graff, Bao Dao, Rebecca Young, Lloyd Earl Damon, Thomas G. Martin, Rebecca Leah Olin
Journal: Journal of Clinical Oncology (2016)

79 Background: Hospitalized patients on the heme/BMT service at our academic cancer center have historically not received pharmacologic VTE prophylaxis (VTEP) due to concerns regarding thrombocytopenia and bleeding risk. However, a retrospective review of heme/BMT admissions from 2009 to 2013 revealed that 59% of hospital-acquired VTE cases occurred at a platelet count &gt; 50 x 10E9/L, suggesting missed opportunities for VTE prevention. Methods: To implement VTEP on the heme/BMT service, a multidisciplinary quality improvement team developed a pilot intervention with 5 strategies: 1) identification of heme/BMT-specific contraindications to VTEP, 2) standardized use of VTEP for all heme/BMT patients unless contraindications are present, 3) hold parameter for platelet count &lt; 50 x 10E9/L within the VTEP order, 4) note template to document VTEP plan, and 5) provider, nurse, pharmacist, and patient education. We conducted audit and feedback every two weeks for two process measures: VTEP ordered for eligible patients (pre-pilot VTEP ordered for &lt; 1%) and VTEP plan documented (pre-pilot documentation of 23%). Patients on therapeutic anticoagulation were excluded. We also tracked major bleeding events among patients receiving VTEP. Results: Since pilot implementation in July 2015, 105 patients admitted during audit periods met the inclusion criteria; 11 patients on therapeutic anticoagulation were excluded. Contraindications to VTEP were present for 56 patients, most commonly platelet count &lt; 50 x 10E9/L (46%), central nervous system lymphoma (23%), and anticipated procedure (21%). Among the 49 eligible patients, VTEP was appropriately ordered for 42 (86%). VTEP plan was documented for 102 patients (97%). One VTEP-associated bleed occurred in a patient with recent polypectomy, prompting the addition of a new contraindication for recent procedures. Conclusions: Our multidisciplinary pilot successfully improved VTEP orders for eligible heme/BMT patients from &lt; 1% to 86% and VTEP plan documentation from 23% to 97%. Rates of hospital-acquired VTE and major bleeding are being tracked prospectively to evaluate efficacy and safety.
Second-line therapy in follicular lymphoma in the United States: Report of NLCS observational study.
Authors: B. K. Link, T. P. Miller, M. Byrtek, J. R. Cerhan, A. D. Zelenetz, H. Dillon, C. Flowers, J. W. Friedberg
Journal: Journal of Clinical Oncology (2011)

8049 Background: The National LymphoCare Study (NLCS) collects data on disease presentation, treatment patterns, and clinical outcomes for 2736 patients with with follicular lymphoma diagnosed 2004-2007 in the USA. Patterns of initial management (Rx1) in this cohort were reported previously (Friedberg, JCO 2009). The current report describes patterns of second-line therapy (Rx2). Methods: Data from pts enrolled in NLCS with a diagnosis of FL and active Rx1 were analyzed to establish patterns of Rx2. Therapy after initial period of observation is considered Rx1 for this analysis. Results: Of 2736 pts enrolled, 1841 remain in active follow-up after median 4.9 years and 991 had received Rx2 with median TTRx2 from Rx1 of 11.1 mos. 325 began Rx2 within six months of beginning Rx1, and 521 within a year. Thus far, 252 pts have begun Rx2 > 2 yrs following Rx1. 89% of Rx2 were for progressive disease, 10% toxicity, and 1% both. Seventy-one (7.3%) of the 991 received XRT monotherapy, 62 (6.3%) received therapy as part of a clinical trial and the rest received systemic therapy – most frequently rituximab plus chemotherapy (36.1%, median TTRx2 9.1mos) and rituximab monotherapy (32.4%, median TTRx2 14.1mos). 82 pts received chemotherapy alone, 33 received radioimmunotherapy, and 15 underwent BMT as part of Rx2. Among 461 pts receiving non-investigational chemotherapy, 154 received an anthracycline (median TTRx2 6.4 mos), 270 did not (median TTRx2 9.5mos) and 37 had incomplete data. After Rx2, 61% of pts remained anthracycline naive. Of pts who received investigational therapy as Rx2, 25.8% had received investigational therapy as Rx1, compared to 6.2% for the remaining Rx2 groups. Conclusions: Among the first half of NLCS pts who have received Rx2, a few notable patterns emerge: R-monotherapy is utilized more frequently as Rx2 than as Rx1; rituximab is again utilized frequently as part of Rx2, even when TTRX2 is short, presumably representing rituximab resistance by common definitions; and most pts remain anthracycline naïve. These data give some clarity to the characteristics of pts available for clinical research in the relapsed/refractory setting of FL, although patterns may change as pts who have longer interval to Rx2 are included over time.
Updated patient reported outcomes and survivorship care plan use by survivors of colorectal cancer (CRC).
Authors: James M. Metz, Margaret K. Hampshire, Carolyn Vachani, Gloria A. Di Lullo, Christine Hill-Kayser
Journal: Journal of Clinical Oncology (2014)

527 Background: Colorectal cancer patients may be at risk for late effects after treatment, the impact of which may difficult to evaluate using conventional methods. Here, we described patient reported outcomes after CRC, as well as use of survivorship care plans. Methods: Patient-reported data were gathered via a convenience sample frame from CRC survivors voluntarily utilizing a publically available, free, Internet-based tool for creation of survivorship care plans. Available at www.livestrongcareplan.com and through the OncoLinkwebsite, the tool allows survivors to enter data regarding diagnosis, demographics, and treatments, and provides customized guidelines for future care. During use of the tool, CRC survivors are queried regarding late effects associated with specific treatments, and asked to answer “yes,” “no,” or “I don’t know.” They are also asked to score GI toxicity using WHO criteria. All data have been maintained with IRB approval. Results: 657 CRC survivors utilized the care plan and answered queries regarding late effects; 64% were female and 82% Caucasian. Median diagnosis age was 50 (24 – 76) and median current age 54 (24 – 77). Many reported having had multimodality therapy - 97% surgery, 89% chemotherapy, and 37% radiation. Overall, 63% reported chronic changes in bowel patterns, 38% chronic diarrhea, 9% bowel obstruction, 18% hernia development, 8% radiation colitis, and 2% fistula formation. Of 249 survivors who graded GI toxicity, 23% reported 4-6 stools per day, and 18% &gt; 6 stools per day or incontinence. When queried regarding sexual function, 35% of men reported worse erectile function than pre-treatment, and 42% of women reported sexual changes such as vaginal dryness. A follow-up survey was completed by 31 (5%) of users, who reported that care plans improved knowledge about late effects (90%) and potential related treatments and tests (83%). Conclusions: Survivors using this tool report significant toxicity after cancer treatment, mainly related to GI and sexual function. Survivors appear to gain knowledge from survivorship care plans. The data reported here may be of significant impact in future study of quality of life, as well as patient counseling and survivor care.
Topoisomerase II and chemosensitivity for pegylated liposomal doxorubicin (pld) used in the third-line treatment of patients with metastatic bladder cancer.
Authors: A. Rozzi, A. P. Mancuso, F. Recine, C. Nardoni, M. Corona, M. R. Restuccia, M. Salerno, F. Bordin, T. Falbo, G. Lanzetta
Journal: Journal of Clinical Oncology (2011)

e15055 Background: PLD has been suggested to provide an option for advanced bladder cancer (Winquist et al., EJC, 2003; Vail et al., Sem Oncol, 2004). It is a totally synthetic 9-aminoanthracyclin and converted by carbonyl reductase I (CBR-I) to its active form, amrubicinol, that has higher potent activity than the parent drug and inhibits purified human topoisomerase II (topo-II). Using tissue samples in selected patients, the clinical significance of topo-II and CBR-I expression levels on antitumor effect as well as toxicity has been examined. Methods: Total RNA was extracted from the tissues with an RNeasy Mini Kit (Qiagen Inc.) and DNase treatment was performed using the RNase-Free DNase Set (Qiagen Inc.). RT-PCR analysis was performed using TaqMan technology. Quantification of target cDNA (Top-II alpha, CBR-I and beta-actin gene) was conducted using an ABI PRISM 7700 Sequence Detection System (Applied Biosystems Inc.). Quantification was performed using the relative standard curve method. Results: The trial registered a total of 42 patients, of which 19 tissue samples were available. Nineteen patients achieved a overall growth tumor control according to the RECIST assessment and 23 did not. Patients with disease control > 4 months had a significantly lower Topo-II level than those without (p=0.0465, Wilcoxon test), although there was no association between tumor response and the level of CBR-I (p=0.3229, Wilcoxon test). We did not find any significant association between the levels of the two enzymes and toxicity. Conclusions: Topo-II may be a potential predictor of response in the treatment of PLD for third-line advanced bladder cancer. Further investigations in larger patient materials are warranted.
Use of advanced imaging and biomarker tests for post-treatment surveillance in early-stage breast cancer survivors.
Authors: Erin E. Hahn, Kaizeen C. Mody, Amy Ann Jacobson, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2012)

168 Background: The American Society of Clinical Oncology (ASCO) released a “Top Five” list of opportunities to improve the quality of cancer care. #4 focused on post-treatment surveillance in breast cancer patients treated with curative intent. The ASCO guideline on breast cancer follow up advises against using advanced imaging and biomarkers in this setting. We undertook an examination of the patterns of follow-up care for breast cancer survivors treated at an academic medical center to evaluate use of non-recommended services. Methods: Claims data and medical records were reviewed and abstracted for early stage (0-IIIA) breast cancer survivors starting one year post diagnosis, with an average of 5 years of follow-up data. A trained abstractor classified imaging tests as diagnostic/surveillance based on medical record content. A 10% random sample was abstracted by a second abstractor and compared for concordance. Descriptive statistics were generated for patient demographic and medical characteristics, and proportions for receipt of non-recommended services, including if imaging procedures were performed for diagnostic/surveillance purposes. Multivariate logistic regression modeling was used to determine factors associated with receiving non-recommended services. Results: Records were available for 258 patients. The mean age was 62 (SD 13), mean time since diagnosis was 6 years (SD 2), 66% were stage 0/1. 35% received at least one abdominal CT, 31% at least one chest CT, 20% at least one PET, 30% at least one bone scan. Of these services, 90 abdominal CT scans (47%), 131 chest CT scans (65%), 77 PET scans (90%), and 29 bone scans (26%) were classified as surveillance. 80% received CEA and/or CA 27.29 tests; 8% received CA 15-3 tests. Logistic regression revealed no consistent association of medical, demographic, or provider factors with receiving non-recommended services. Conclusions: Use of non-recommended services for surveillance occurs frequently among early stage survivors. Providers in this academic center had no personal financial incentive for ordering these services. There are opportunities to increase use of guideline concordant post-treatment care for breast cancer survivors.
Biologic activity of dasatinib administered as neoadjuvant therapy preceding radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC).
Authors: Beatrice Knudsen, Noah M. Hahn, Siamak Daneshmand, Edwin M. Posadas, Sambit Muhanty, Seth P. Lerner, Guru Sonpavde
Journal: Journal of Clinical Oncology (2014)

324 Background: Dasatinib (D) is an oral tyrosine kinase inhibitor of Src mediated signaling, and has demonstrated promising preclinical anti-tumor activity in bladder cancer with activated Src (Sonpavde G, Mol Cancer Ther, 2010). We previously reported the feasibilty of neoadjuvant D before RC for MIBC in a phase II trial (Hahn NM, ASCO, 2012). Here, we report correlative tumor tissue studies. Methods: A phase II trial (N=25) was conducted to assess the safety and biologic activity of neoadjuvant D in cT2-T4a, N0, M0 bladder cancer patients (pts) unsuitable for or willing to forego platinum-based neoadjuvant therapy. Patients received D 100 mg po once daily for 28 +/- 7 days followed by RC 8-24 hours after the last dose. Correlative studies evaluated tissues from baseline biopsy and RC for expression of phosphorylated (p) SRC family kinases (SFK) by immunohistochemistry (IHC). pSFK expression was scored on a scale from 0 - 3 by 2 pathologists. Results: The study completed accrual with enrollment of 25 patients. Both baseline and RC tumor were available and adequate for correlative studies in 14 cases. In 5 additional cases, carcinoma was available for baseline or RC tumor only. All pre- and post-treatment tissue samples demonstrated positive staining by IHC in inflammatory cells, which were used as the internal positive control. In all cases, the cancer cells were positive before treatment and the staining decreased after treatment. In 6 cases there was no detectable staining after treatment. In 9 cases (66%), pSFK levels decreased by 2 units from 2.5-3 pre-treatment to 0.5-1 post-treatment. In 5 cases, levels declined &lt;2 units and of these, 2 demonstrated weak staining before treatment (0.5 and 1).In a separate tissue microarray from 20 RC specimens, 15 (75%) bladder cancers demonstrated pSFK expression, while all 40 control kidney and prostate cancers were negative. Conclusions: Neoadjuvant D demonstrated biologic activity in MIBC with marked decrease of pSFK in 66% of cases, while the remaining showed smaller decreases. This study also demonstrates frequent and high expression of pSFK at baseline in MIBC, suggesting that evaluation of D may be justified in a broad population.