tbuckley/cabot-search huggingface dataset:
Adjuvant high-dose intensity-modulated radiotherapy following radical prostatectomy: Updated 5-year results.
Authors: P. Ost, B. De Potter, A. Beerens, N. Lumen, V. Fonteyne, G. De Meerleer
Journal: Journal of Clinical Oncology (2011)

69 Background: Approximately 25% of patients treated with immediate post-prostatectomy (adjuvant) radiotherapy will develop a biochemical failure within 5 years after radiotherapy when doses of 60-64 Gy are used. We wanted to report on the safety and biochemical outcome of adjuvant intensity-modulated radiotherapy (AIMRT) with a median dose of 74 Gy. Methods: Between 1999 and 2008, 104 patients underwent a radical prostatectomy followed by AIMRT +/− androgen deprivation (AD). Indications for AIMRT were capsule perforation, seminal vesicle invasion and/or positive surgical margins at prostatectomy specimen. All patients were irradiated at a single tertiary academic centre. AD was initiated in 65% of the patients on the basis of seminal vesicles invasion, pre-prostatectomy PSA &gt; 20ng/mL, Gleason score ≥ 4+3 or personal preference of the referring urologist. A median dose of 74 Gy was prescribed to the planning target volume using IMRT in all patients. AD consisted out of a LHRH analogue for 6 months. The Kaplan-Meier method was used to estimate biochemical relapse-free survival (bRFS). Univariate and multivariate analysis were used to examine the influence of patient- and treatment-related factors on bRFS. Results: The median follow-up was 5 years. Late toxicity: no patients developed grade 3 gastrointestinal (GI) toxicity. Grade 2 GI toxicity was seen in 8%. Seven patients (7%) and 24 (23%) developed grade 3 and 2 genitourinary (GU) toxicity, respectively. An urethral stricture was observed in 8 patients (8%). The 3- and 5-year actuarial bRFS was 91% and 85%, respectively. On univariate analysis bRFS rates was reduced with seminal vesicle invasion (p &lt; 0.04) or Gleason score ≥ 4+3 (p &lt; 0.02) or negative margins (p &lt; 0.001). AD and preoperative PSA levels did not influence bRFS. None of the variables remained significant on multivariate analysis.Eight patients had a distant clinical relapse (pelvic lymph nodes: 3, bone metastases: 3 and 2 patients had both). Seven patients died (3 prostate cancer related deaths). Conclusions: Adjuvant high-dose IMRT after prostatectomy is safe. Five-year bRFS is excellent. No significant financial relationships to disclose.
Results of a phase II trial of sirolimus (S) and cyclophosphamide (C) in advanced sarcoma.
Authors: S. Schuetze, L. Zhao, R. Chugh, M. Zalupski, D. Thomas, D. R. Lucas, L. H. Baker
Journal: Journal of Clinical Oncology (2011)

10003 Background: Activation of the PI3-kinase/AKT/mTOR pathway has been demonstrated in sarcoma sub-types. Trials of single-agent mTOR inhibitors in sarcoma have shown low objective response rates but progression-free survival (PFS) rates suggest possible cytostatic effect. The combination of S and C demonstrated anti-sarcoma activity in Pediatric Preclinical Testing Program models. Methods: We conducted a phase II Simon Minimax trial of S (12 mg dose on day 1 followed by 4 mg daily) and C (200 mg orally daily for 7 days every other week) in patients (pts) with advanced bone or soft tissue sarcoma. Dose of S and C were reduced for grade ≥3 toxicity. C was held for neutrophil <1K or platelet <75K. Primary objective was to estimate 6-month PFS rate with a target of ≥25%. Pts were followed for tumor response (WHO criteria) by imaging every 2 months. Sirolimus serum levels were measured after 4 weeks; lipid and plasma VEGF levels were measured before and after 4 weeks of treatment. Archived tumor tissue was analyzed for total and phosphorylated mTOR and S6 by quantitative immunofluorescence. Log rank test and cox regression analyses were used to evaluate survival endpoints. Results: 49 eligible pts (21F/28M) were enrolled from 9/08-12/09. Median age was 57 years (range 19-82) and number of prior therapies was 2 (1-6). 16 pts had leiomyosarcoma, 9 liposarcoma, 6 undifferentiated, 6 bone and 12 other sarcoma subtype. Median/mean trough S level was 8.7/9.7 ng/ml (range 1.3-25.8). 2 pts each experienced grade ≥3 dyspnea, thrombosis, cystitis and 3 pts grade 3 infection; 3 deaths on treatment were attributed to disease progression. 10 of 47 evaluable pts were progression-free for ≥6 months and 2 completed >12 months of treatment. Median PFS was 103 days, and 6-month PFS rate was 21% (SD: 0.06%). Median survival was 328 days. Normal triglyceride level at baseline and lower level of mTOR pathway activation correlated with longer PFS (p=0.02 and p=0.05) and overall survival (p=0.06 and p=0.03). VEGF plasma levels did not correlate with outcome. Conclusions: Combination of S and C was tolerated by most patients and 1/5th had stable sarcoma for ≥6 months. Contrary to hypothesis, sarcomas with higher level of mTOR activation showed earlier progression on S.
MammoSite partial breast irradiation following breast-conserving surgery for early-stage breast cancer.
Authors: O. Shokek, S. Yacoub, T. L. Bauer, T. Bell, G. A. Fortier, R. Grim, R. E. Hempling, D. E. Johnson, B. Kassas, D. Lasher, K. Mudge, S. Pandelidis, R. Pramanik, M. Watson, J. Wojcicka, A. Shah
Journal: Journal of Clinical Oncology (2011)

122 Background: Partial breast irradiation (PBI) remains investigational until comparisons to whole-breast external beam radiotherapy (EBRT) confirm noninferiority. Methods: From 2004 to 2010, 103 patients at York Cancer Center (Pennsylvania) who underwent margin-negative breast-conserving surgery for early-stage invasive or in situ breast carcinoma were enrolled on a prospective MammoSite PBI protocol. NSABP B39 stage and planning criteria were utilized, with unicentric tumors up to 3 cm and pN0-1 axillary staging for invasive carcinomas. PBI was prescribed to 1 cm from the applicator surface in 10 twice-daily fractions to 34 Gy. Results: With a median follow-up of 27 months, three patients experienced recurrence: one with isolated local in-breast tumor recurrence (local IBTR), one with IBTR remote from the surgical cavity (non-local IBTR) plus regional and distant recurrence, and one with regional and distant recurrence only 3- and 5-year freedom from local IBTR are 100% and 96% (non-local IBTR: 100% and 95%). Physician-reported cosmesis evaluations are available for 25 patients at 2-3 years after treatment, with a median score of “excellent.” 26 additional patients on protocol underwent insertion of the MammoSite applicator but had it removed without treatment, most commonly due to unsatisfactory cavity conformance (24 patients), uncommonly due to infection or seroma (two patients). Their characteristics (invasive vs. in situ disease, T/N stage, negative vs. close margins, age) were not statistically different than the 103 MammoSite-treated patients. All except one received EBRT, and none experienced IBTR, which is not statistically different than the IBTR rates of the 103 MammoSite-treated patients (p=0.84). Conclusions: MammoSite PBI in well-selected patients was associated with low rates of IBTR and not significantly different than a comparison cohort selected for MammoSite PBI but treated instead with EBRT. Randomized comparisons of PBI vs. EBRT are required to confirm PBI as standard.
Multivariate Analysis Evaluating Potential Predictors of Cardiac T2* Where Cardiac Magnetic Resonance Imaging (CMR) Availability Is Limited
Authors: John B Porter, Ali T Taher, Yesim Aydinok, Amal El-Beshlawy, Mohsen El-Alfy, Ali El-Ali, Subhashish Chakravarty, M Domenica Cappellini
Journal: Blood (2014)
Multicenter prospective phase II study of sunitinib in non-clear cell type renal cell carcinoma.
Authors: J. Lee, J. Ahn, H. Lim, S. Lee, T. Kim, D. Lee, Y. M. Cho, J. Hong, C. Kim, H. Ahn
Journal: Journal of Clinical Oncology (2011)

325 Background: Sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) in patients (pts) with clear cell RCC. Retrospective data suggest sunitinib may be effective in papillary and chromophobe RCC. We conducted a multicenter phase II trial of sunitinib in non-clear cell RCC (nccRCC). Methods: Eligibility criteria included PS 0-1, measurable disease, and adequate organ function. Pts with brain metastases were not excluded if controlled without steroid dependence. Response assessment was performed every 6 weeks. Primary endpoint was RR. Secondary endpoints were TTP, safety and OS. Results: Between 6/2008 and 7/2010, 29 pts with nccRCC were enrolled (total accrual 35: P 0 =5%, P 1 =20%, alpha=0.05, beta=0.2, drop-out rate 15%). Median age was 52 (18–76). Twenty-four pts (84%) had prior nephrectomy. Seven pts (24%) had poor risk and 13 (45%) had intermediate risk disease by MSKCC criteria. Twenty-one pts had papillary RCC (type II in 11 and type not- specified in 10), and 4 patients had chromophobe RCC. Two pts discontinued protocol treatment due to toxicity prior to completion of cycle 1 (one pt had cardiogenic shock 27 days after start of therapy and the other refused further treatment 5 days after therapy). Eleven pts out of 29 had partial response with a RR of 38% (95% CI, 20.2%–55.6%) and additional 15 patients (52%) had SD with a disease control rate of 90%. Response rates were not significantly different according to the histologic type (43% in papillary type and 25% in chromophobe type). Median duration of response was 12.7 months (95% CI, 2.3∼23.1) and median TTP was 6.4 months (95% CI, 4.5∼8.3). With a median FU duration of 16 months (95% CI, 8.6∼23.4), 10 pts have been dead resulting in an estimated median OS of 17.9 months. Toxicity profiles were commensurate with prior reports on Korean patients (Yoo, et al. Jpn J Clin Oncol 2010). However, there was one treatment-related death caused by acute heart failure in patient without relevant risk factors for heart disease. Conclusions: Although our study is ongoing, the primary endpoint has been met and these data suggest that suntinib has promising activity in patients with nccRCC. No significant financial relationships to disclose.
The use of complementary and alternative medicine (CAM) by Irish patients with breast cancer.
Authors: D. M. Graham, N. A. O'Connor, J. McCaffrey, D. N. Carney
Journal: Journal of Clinical Oncology (2011)

259 Background: Worldwide, the use of complementary and alternative medicine (CAM) has greatly increased over the last decade. CAM use has been shown to be higher in cancer patients than among the general population and is known to be prevalent in patients with breast cancer. The aim of this study was to investigate the prevalence of CAM use among Irish breast cancer patients; something which has not previously been examined. Methods: An anonymous cross-sectional survey was offered to all patients attending for treatment of malignancy or cancer-care follow-up at a single Irish Cancer Centre over an 8-week period. The reasons for CAM use and those factors that increase the likelihood of CAM use were also investigated. A subset analysis of patients with a diagnosis of breast cancer was performed. Results: A total of 230 questionnaires were distributed. 193 patients responded. Of these, 5 were excluded due to lack of demographic data. Of the 188 surveys available for analysis, 91 respondents (49%) had a diagnosis of breast cancer. Thirty-five breast cancer patients (39%) reported having used CAM. This was not significantly different from other cancer types. Of those patients with breast cancer who used CAM, 11 (12%) commenced CAM use following their cancer diagnosis. Respondents who were under 40 (p=0.005), single (p=0.023) and currently in employment (p=0.001) were more likely to use CAM. The most common reason cited for CAM use was to improve physical well-being (46%) and 78% reported a benefit. No patients reported adverse effects from CAM use. The most commonly used therapies were massage/reflexology (58%), relaxation therapy (61%) and herbal teas (58%). CAM medication therapies were used by 31% CAM users, of whom 32% had not informed their doctor. Conclusions: CAM use is prevalent among Irish breast cancer patients. Use of CAM is more common in young, single, employed patients, in keeping with similar studies in other countries. A significant proportion use CAM medications, which may potentially interact with prescribed treatment. Of note, almost one third of these patients do not inform their doctor. This underlines the need for physicians to ask about CAM use in all patients being treated for breast cancer.
Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial
Authors: Arjun V Balar, Matthew D Galsky, Jonathan E Rosenberg, Thomas Powles, Daniel P Petrylak, Joaquim Bellmunt, Yohann Loriot, Andrea Necchi, Jean Hoffman-Censits, Jose Luis Perez-Gracia, Nancy A Dawson, Michiel S van der Heijden, Robert Dreicer, Sandy Srinivas, Margitta M Retz, Richard W Joseph, Alexandra Drakaki, Ulka N Vaishampayan, Srikala S Sridhar, David I Quinn, Ignacio Durán, David R Shaffer, Bernhard J Eigl, Petros D Grivas, Evan Y Yu, Shi Li, Edward E Kadel, Zachary Boyd, Richard Bourgon, Priti S Hegde, Sanjeev Mariathasan, AnnChristine Thåström, Oyewale O Abidoye, Gregg D Fine, Dean F Bajorin
Journal: The Lancet (2016)
Effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor, on chemotherapy and antiangiogenic response in pancreatic cancer.
Authors: Katherine T. Ostapoff, Niranjan Awasthi, Peter L. Yen, Changhua Zhang, Margaret A. Schwarz, Rolf A. Brekken, Roderich Schwarz
Journal: Journal of Clinical Oncology (2012)

243 Background: The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathway dysregulation is a prominent feature of pancreatic ductal adenocarcinoma (PDAC). Gemcitabine (GEM), a standard systemic treatment for PDAC, has limited clinical benefits. The present study investigated the effects of NVP-BEZ235 (BEZ235), a novel dual PI3K/mTOR inhibitor, in combination with gemcitabine and endothelial monocyte activating polypeptide II (EMAP) in experimental PDAC. Methods: Protein expression and cell proliferation were analyzed by Western blotting and WST-1 assay. Animal experiments were performed in murine xenografts. Results: BEZ235 inhibited phospho-AKT (Ser473) and phospho-mTOR (Ser2448) expression in PDAC (AsPC-1), endothelial (HUVECs) and fibroblast (WI-38) cells. NVP-BEZ235 also caused a significant dephosphorylation of downstream mTORC1 target proteins phospho-p70 S6K (Thr389) and phospho-4E-BP1 (Thr37/46). In vitro 72-hour proliferation of four PDAC cell lines was significantly inhibited by BEZ235. Additive effects on proliferation inhibition were observed in the BEZ235 and GEM combination in PDAC cells and in combination of BEZ235 or EMAP with gemcitabine in HUVECs and WI-38 cells. BEZ235, alone or in combination with GEM and EMAP, induced apoptosis in AsPC-1, HUVECs and WI-38 cells as observed by increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. PDAC in vivo therapy demonstrated that compared to controls (median survival: 16 days), animal survival increased after BEZ235 and EMAP therapy alone (both 21 days) and GEM monotherapy (28 days). Further increases in survival occurred in combination therapy groups BEZ235+GEM (30 days, p=0.007), BEZ235+EMAP (27 days, p=0.02), GEM+EMAP (31 days, p=0.001) and BEZ235+GEM +EMAP (33 days, p=0.004). Conclusions: BEZ235 has experimental PDAC antitumor activity in vitro and in vivo that can be enhanced in combination with cytotoxic (GEM) and antiendothelial (EMAP) agents. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment.
What has changed in the management of breast cancer in the past 25 years at the Istanbul University Hospital?
Authors: F. Aydogan, E. Gazioglu, E. Canbay, I. Aydin, T. Aydogan, C. Uras, V. Celik, A. Cengiz, M. Ferahman, H. Unal
Journal: Journal of Clinical Oncology (2011)

184 Background: There have been important changes in diagnosis and treatment of the breast cancer during the last century. Diagnosing the cancer in early stages brought the new approaches such as breast conserving surgery instead of mastectomy and sentinel lymph node biopsy instead of direct axillary disection. In this study our purpose is to compare the operations which were performed in 1983 and 2008 on breast cancer patients of our clinic and to search the differences in their ages and tumor characteristics. Methods: In each group the files of 100 patients, who were operated in 1983 and 2008, were compared with each other including the variabilities such as size of the tumor, age of the patient and operation technique. Results: There were 100 patients in both of the groups. Six of the patients (6%), who were operated on in 1983, were found to be between the ages of 20-39 and this percentage was found to be much higher as 19% (19 patients) in 2008. In 1983, there wasn't any patient at stage 0 and the number of patients at stage 1 was 15 (15%), in 2008 the number of stage 0 patient was 9 (9%) and stage 1 patient was 25 (25%). Breast conserving surgery rate was found to be 9% in 1983 and 41% in 2008. Conclusions: According to the data of this study, breast cancer is now being seen at younger ages when compared to 25 years ago. Currently the patients have diagnosis at earlier stages and the breast conserving surgery is much more prevalent. Earlier-stage diagnosis can be explained by widespread use of screening mamographies and increasing consciousness of the patients.
The East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer.
Authors: R. E. Raab, P. R. Walker, L. S. Bellin, J. H. Wong
Journal: Journal of Clinical Oncology (2011)

e11505 Background: Triple negative (ER, PR, and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy limiting treatment options to cytotoxic chemotherapy alone. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients with TNBC >/= 2 cm were eligible (including locally advanced or inflammatory breast cancer). Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Patients received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between July 2006 and December 2010, 12 patients with TNBC were enrolled, 9 are eligible for analysis. Accrual continues to date. Age ranged from 25 to 85 (mean age 46.5 + 16.3yrs), primary tumor size ranged from 2.5 cm to 12.0 cm (mean 5.8 cm + 2.9cm). Three patients had clinically positive lymph nodes. Of the 8 patients who underwent sentinel node biopsy prior systemic therapy, 4 patients were staged pN0 and 4 were staged pN positive. One patient experienced G3 thrombocytopenia, two patients G3 granulocytopenia, one patient G3 anemia and one patient G3 neuropathy. One patient died of a pulmonary embolus possibly related to therapy. Rate of clinical CR was 66%, rate of clinical PR was 33%, and one patient progressed on therapy. The rate of complete pathologic response was 66%. One patient had a 0.7 cm focus of residual invasive carcinoma. Positive nodes were identified in 22%- one patient who progressed on therapy and one who experienced a clinical PR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus oral cyclophosphamide followed by weekly paclitaxel plus carboplatin is well tolerated. These results suggest significant activity of this approach in women with triple negative breast cancer and warrants continued investigation.
Terminal Complement Inhibitor Eculizumab Improves Complement-Mediated Platelet Consumption and Thrombocytopenia in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH).
Authors: Gerard Socie, Petra Muus, Hubert Schrezenmeier, Britta Höchsmann, Jaroslaw P. Maciejewski, Ilene Ceil Weitz, Anita Hill, Monica Bessler, Antonio M. Risitano
Journal: Blood (2009)
Chemotherapy-induced amennorrhea: Predictive markers of response to neoadjuvant chemotherapy in breast cancer.
Authors: S. K. Ahn, H. Moon, E. Ko, J. s. Kim, J. M. You, H. Shin, W. Han, D. Noh
Journal: Journal of Clinical Oncology (2011)

281 Background: There is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated significance of CIA after neoadjuvant chemotherapy for predicting response to neoadjuvant chemotherapy in breast cancer patients. Methods: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. Results: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 vs. 38.27± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 mIU/ml vs. 45.76±30.31 mIU/ml; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly predictive of tumor response. CIA was only significant predictive factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). Conclusions: CIA is independent predictive markers of response to neoadjuvant chemotherapy in locally advanced breast cancer.
Downregulation of BAP1 in Chronic Myelomonocytic Leukemia: Correlated with a Post-Translational Reduction of BRCA1 Levels and Independent of Promoter Methylation
Authors: Ana María Hurtado, Gines Luengo-Gil, Laura Palomo, Eva Lumbreras, Eva Caparrós, Tzu Hua Chen-Liang, Bartlomiej Przychodzen, Maria Luz Amigo, María Díez-Campelo, Lurdes Zamora, Francisco José Ortuño, Raul Teruel Montoya, Jaroslaw P. Maciejewski, Consuelo Del Cañizo, Francesc Sole, Francisca Ferrer-Marin, Andres Jerez
Journal: Blood (2015)