tbuckley/cabot-search huggingface dataset:
Phase II study of the combination of gemcitabine plus carboplatin as neoadjuvant treatment in locally advanced breast cancer.
Authors: V. Srimuninnimit, S. Ithimakin, C. Akewanlop, A. Ratanawichitrasin, V. Veerasan, S. Rojananin, P. Prasartong-osoth
Journal: Journal of Clinical Oncology (2010)

652 Background: Although anthracycline-based regimen is standard neoadjuvant chemotherapy for locally advanced breast cancer (LABC), there is some concern about its toxicities such as alopecia and cardiotoxicity. Gemcitabine is another active agent in metastatic breast cancer after failure to anthracycline with less toxicity. The objective of this study is to evaluate efficacy and safety of combination of gemcitabine and carboplatin as induction chemotherapy in LABC. Methods: Patients with histologically confirmed LABC (T3, T4 or N2 and M0) were included. Patients were scheduled to receive 3 cycles of neoadjuvant GC (gemcitabine 1,000 mg/m2 D1, D8 and carboplatin AUC×5) every 21 days. Patients with clinical response underwent surgery and additional 3 cycles of adjuvant GC. Those with clinical stable or progressive disease were taken off study and received standard anthracycline-based regimen. All patients were scheduled for adjuvant radiation and hormonal treatment depending on hormonal status. Primary end point was pathological response rate whereas secondary end points included PFS, OS and toxicity. Results: Between July 2004 and July 2007, 40 patients were enrolled. The median age was 46 years. Twenty-three patients (57.5%) had T4 lesion and 17 (42.5%) had T3. Out of 40 patients, 37 were evaluable for efficacy and 40 for toxicity. Twenty-four out of 37 patients (65%) obtained cPR. Among 23 patients who had clinical response underwent modified radical mastectomy, overall pathological response rate was 51.4% with 1-pCR (2.7%) and 18-pPR (48.6%). All 6 triple-negative patients had pathological response (1-pCR, 5-pPR). At median follow up of 35 months, median PFS and OS were not reached. Two-year OS and PFS were 81.2 % and 60.8 %, respectively. Common grade III and IV adverse effects were neutropenia (67.5%), anemia (45%) and thrombocytopenia (37.5%). Four patients developed grade III hepatitis with complete resolution after discontinuation of GC. No patient developed febrile neutropenia or fatal complications. Conclusions: Combination GC was efficacious, feasible and well-tolerated for LABC in neoadjuvant setting. Triple-negative subgroup seems to have high response to GC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly
Expression profiling-based subtyping of NSCLC and its putative association with response to chemotherapy.
Authors: J. Hou, L. Lambers, B. d. Hamer, M. d. Bakker, H. Hoogsteden, F. Grosveld, J. Hegmans, J. Aerts, S. Philipsen
Journal: Journal of Clinical Oncology (2011)

e21111 Background: A challenge of cancer therapy is to optimize therapeutical options to individual patients. Cancers with similar histology may show dramatically different responses to therapy, indicating that a refined approach needs to be developed to classify tumors by intrinsic characteristics that may predict response to chemotherapy. Global expression profile-based classification has the potential to identify such tumor-intrinsic subclasses. Methods: Ninety-one non-small cell lung cancer (NSCLC) tumors were profiled using mRNA microarray. Unsupervised clustering was performed to identify molecular subclasses of NSCLC. The relevance of these molecular subclasses was linked to other clinical and histopathological characteristics. Results: The global expression profiles classified NSCLC into six subclasses with mixed histology. One of the subclasses with adenocarcinoma (ADC) and large cell carcinoma (LCC) was correlated to putative resistance to pyrimidine synthesis inhibitor (pemetrexed). Conversely, a subset of squamous cell carcinoma (SCC)had predicted therapeutic benefit from this agent. The distinct molecular attributes of NSCLCs resistant to pemetrexed were bioinformatically characterized. For instant clinical selection of putative responders to Pemetrexed, we tested the expression of eight routine histological markers and identified that the expression of these markers, cooperated with refined molecular classification of NSCLC, can predict response to pemetrexed. Conclusions: We identified six distinct subgroups of NSCLC based on gene expression profiles. This molecular classification may aid in reliably stratifying patients with respect to the choice of therapeutic agents.
Screening for hepatitis B virus prior to chemotherapy: A quality improvement project.
Authors: Lisa K. Hicks, Patricia Leung, Jennifer Cape
Journal: Journal of Clinical Oncology (2013)

158 Background: Hepatitis B virus (HBV) reactivation is a well-recognized and serious complication of chemotherapy which can be prevented with prophylactic antiviral therapy. St. Michael’s Hospital (SMH) is an academic hospital in Toronto, Canada, serving an inner city population. The prevalence of chronic HBV in populations such as ours is estimated to be &gt; 8%, compared to 2% of all Canadians. In this context, surveillance for HBV prior to chemotherapy is very important. Aim: To increase the HBV screening rate among patients starting IV chemotherapy at SMH to greater than 90% by December 2013. Methods: Repeated plan-do-study-act (PDSA) cycles targeting HBV screening in our chemotherapy unit were initiated in January 2013 and are on-going. Appropriate HBV screening was defined as at least one HBsAg test up to 3 months prior to, or 3 weeks after starting chemotherapy. Interventions included education sessions, posters, standardized HBV lab order sets, and pharmacist review of lab data prior to first chemotherapy with reminders to physicians when HBV testing was absent. Pre and post-intervention HBV screening rates were compared using process control charting. Results: Between January 1, 2012, and June 15, 2013, 407 unique patients started IV chemotherapy at SMH. Prior to our interventions a stable HBV screening rate of approximately 30% was observed. Sequential process improvements were introduced in January and April 2013. Process control charting demonstrated the presence of special cause variation subsequent to our interventions with a significant improvement in the HBV testing rate (post-intervention rate of 70%). The HBV testing rate began to improve in January 2013 and met criteria for special cause variation by February 2013. Conclusions: It is possible to dramatically increase the rate of HBV testing prior to chemotherapy through relatively simple, low tech process improvements. Further improvements are necessary to reach our goal of a 90% HBV screening rate prior to IV chemotherapy. Additional planned interventions include individualized physician report cards on HBV screening rates using achievable benchmark criteria and an education campaign directed at empowering patients to ask about HBV testing.
Phase I trial of SNS-595 in patients with advanced malignancies
Authors: R. Advani, M. Gordon, H. Hurwitz, D. Mendelson, H. Wakelee, S. Ebbinghaus, U. Hoch, J. Silverman, N. Havrilla, D. Adelman
Journal: Journal of Clinical Oncology (2005)

2099 Background: SNS-595 is a novel naphthyridine analog that induces a G2 cell cycle arrest in vitro and shows broad activity in xenograft and drug resistant tumor models. Methods: SNS-595 was administered to patients (pts) with advanced solid cancers every 3 weeks as an IV infusion over 10 minutes without premedications. Cohorts of 3–6 pts were accrued to doses based on a modified Fibonacci sequence. Results: As of 12/04 16 patients were treated in the first five cohorts at doses starting at 3 mg/m2 and advancing to 48 mg/m2. Tumor types included lung (4), adenocarcinoma of unknown primary (4), renal (3), ovarian, melanoma, bladder, sarcoma and cholangiocarcinoma (1 each). The median age was 57 years (range 46 to 74) and median ECOG PS was 1 (range 0–2). No dose limiting toxicity has been seen. Transient Grade 4 hematological toxicity (ANC <500/μL) was seen in 2 of 3 pts in cohort 5 (48 mg/m2). Non-hematologic toxicities were mild and all grade 1/2. PK samples were collected on treatment Day 1 and were assayed using a noncompartmental analysis. Plasma SNS-595 concentrations were determined using a validated LC-MS/MS assay. AUC increased proportionally with dose and mean AUC(0-Inf) were 6329±182, 12655±851 and 25440±9512 ng*hr/ml, respectively, for 12, 24 and 48 mg/m2 dose levels. The terminal half-life is approximately 19 hours. Conclusions: In this phase I study SNS 595 is well tolerated with consistent and predictable PK effects. Dose escalation is continuing. Further data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sunesis Sunesis Sunesis
Presence of variant histology (VarHst) in transurethral resection of bladder tumor (TURBT) biopsies and its prognostic significance on pathologic complete response (pCR) rates to neoadjuvant chemotherapy (neo-CTx).
Authors: Jose Alexandre Pedrosa, Kevin Rice, Derek E. Thomas, Paul Johnston, Marietta L. Moore, Angela D. Reed, Dylan M. Cregar, Cindy Franklin, Michael O. Koch, Richard Bihrle, Richard Foster, Timothy A. Masterson, Thomas A. Gardner, Chandru Sundaram, Charles R. Powell, Stephen Beck, David A. Grignon, Liang Cheng, Noah M. Hahn
Journal: Journal of Clinical Oncology (2013)

295 Background: Randomized phase III clinical trial data (S8710) supports an overall survival (OS) advantage with neo-CTx for muscle-invasive urothelial carcinoma (miUC) patients (pts) prior to cystectomy. Recent S8710 subset analyses have demonstrated an OS for pts with both pure UC and VarHst. pCR to neo-CTx has been suggested as a surrogate endpoint for OS. The relationship between VarHist in TURBT specimens and pCR rates is uncertain. Methods: A retrospective review of the Indiana University Simon Cancer Center urology and medical oncology clinical databases was performed spanning the years 1991 – 2012. Subjects with miUC, pathology reports available for both TURBT and cystectomy procedures, and confirmed receipt of neo-CTx with regimen details were included in this analysis. Pts with clinically positive lymph nodes (LN+) were included provided they underwent cystectomy with curative intent and distant metastases were not present. Associations between pCR and pt baseline age, gender, race, clinical stage (T2N0 vs. T3/T4/N+), chemotherapy regimen received (cisplatin combination therapy (CisCTx) vs. non-cisplatin based), and presence of VarHst on TURBT sample were tested by multinomial logistic regression analysis with statistical significance set at p&lt;0.05. Results: 72 miUC pts satisfying the inclusion criteria were identified. Cohort demographics included: age (median) – 59 yrs, 76% male, 93% Caucasian, 63% T2N0, 32% LN+, 81% CisCTx neo-CTx regimen, 42% VarHst on TURBT, pCR for entire cohort 18%. The presence of VarHst on TURBT sample was not associated with decreased rates of pCR (6/30 vs. 7/42) p=0.610. A trend toward significance with age over 59 was also observed. Conclusions: The presence of VarHst in TURBT specimen is not associated with decreased rates of pCR at cystectomy in miUC pts treated with neo-CTx. Further characterization of the amount of VarHst and reproducibility of its recognition in TURBT samples is warranted to determine its ultimate clinical value.
Utilizing QOPI in the quality improvement efforts of the NCI Community Cancer Centers Program (NCCCP).
Authors: Robert D. Siegel, Holley Stallings, Donna M. Bryant, Pamela Kadlubek, Laurel Borowski, Kathleen M. Castro, Steven B. Clauser
Journal: Journal of Clinical Oncology (2012)

208 Background: The NCCCP is a network of community based institutions from New England to Hawaii funded by the NCI. Quality of care is a priority of the NCCCP with participation in ASCO’s Quality Oncology Practice Initiative (QOPI) playing a fundamental role. QOPI provides a process for quality assessment but we have also used it as a measure of quality improvement (QI) network-wide. Using QOPI methodology, we have analyzed our performance twice a year in an effort to enhance our implementation of quality indicators relevant to program aims. Methods: A data sharing agreement allows individual practice QOPI data to be electronically sent to the NCI where it is aggregated with the other NCCCP QOPI participants. Data are presented via webinar within the network using a variety of QI strategies. For example, blinded site performance distributions are benchmarked against NCCCP national averages on specific indicators. High performing practices voluntarily present their QI initiatives and best practices to the network. The NCCCP Quality of Care Subcommittee then selects QI projects and areas to focus quality improvement efforts. Results: In Spring 2012, 44 practices affiliated with 25 NCCCP sites participated in QOPI, a consistent pattern since Fall 2010. The table below describes the percent compliance with certain QOPI measures for the NCCCP aggregate over time. Selected measures were perceived as having had suboptimal compliance in Fall 2010. Conclusions: QOPI is an effective tool for assessing quality within a network and for measuring quality improvement efforts. Best practices from within the network can be leveraged and disseminated to enhance the quality of cancer care. This methodology facilitates quality initiatives despite the logistical challenges of working with practices across the country. [Table: see text]
Palliative treatment in extrahepatic biliary malignancies: A multi-institutional cohort.
Authors: Ana Wilson, Cecilia Grace Ethun, George A. Poultsides, Thuy Tran, Kamran Idrees, Chelsea A Isom, Ryan C. Fields, Bradley Krasnick, Sharon M. Weber, Ahmed I. Salem, Robert C. G. Martin, Charles Raben Scoggins, Perry Shen, Harveshp Mogal, Carl Richard Schmidt, Eliza W Beal, Ioannis Hatzaras, Rivfka Shenoy, Shishir Kumar Maithel, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2016)

456 Background: Extrahepatic biliary malignancies (EBM) are often first diagnosed at advanced stages when the disease is no longer surgically resectable. While palliative resection may provide a more definitive solution for patients with jaundice, it also carries a higher risk of complications than endoscopic or percutaneous drainage. Herein, we analysed patients undergoing both methods of palliation to better delineate these risks. Methods: 172 patients who underwent palliative treatment for EBM between 2000 and 2014 were identified from 10 major hepato-biliary centers participating in the EBM Consortium. Clinicopathologic, operative and outcome data were collected and analyzed. We used propensity score matching to correct for confounding by indication. Results: 113 patients underwent surgery with palliative resection of their tumor (65.7%), while 59 underwent diagnostic surgery, but were treated with percutaneous or endoscopic biliary drainage instead of resection (34.3%). Patients who were not resected were more frequently jaundiced preoperatively (p = 0.001), and were more likely to undergo repeat drainage procedures (p &lt; 0.001). After matching for functional status, age, and clinical jaundice, patients who underwent resection had significantly more complications (55.6% vs. 34.0%; p = 0.035), a higher median number of complications (1 vs. 0; p = 0.0149), a higher Clavien Dindo Grade (IIIa vs. II; p = 0.0261), a longer hospital stay (8 vs. 4 days; p &lt; 0.001), and a notable trend towards higher perioperative mortality (10.9% vs. 1.96%; p = 0.069). Meanwhile the postoperative bilirubin level was equal among the resected (1.80 mg/dL (IQR, 0.60-8.90)) and drainage groups (2.45 (IQR 0.60-10.5))(p = 0.477), and both groups had a statistically significant drop after treatment (resection 8.30 mg/dL to 1.80 mg/dL, p &lt; 0.001; drainage 8.4 to 2.45, p &lt; 0.001). Conclusions: Both palliative resection and biliary drainage successfully treated EBM patients’ hyperbilirubinemia. However, in a propensity score matched group, palliative resection patients had more complications and a trend towards more perioperative mortality, urging caution in the selection of patients for these procedures.
Pazopanib in patients with metastatic renal cell carcinoma previously treated with sunitinib or bevacizumab: A Sarah Cannon Research Institute phase II trial.
Authors: J. A. Reeves, D. R. Spigel, D. B. Daniel, E. K. Friedman, H. A. Burris, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2011)

4659 Background: Pazopanib, a multi-targeted inhibitor of VEGFR, PDGFR, and c-KIT, is an active first-line agent in the treatment of advanced renal cell carcinoma (RCC). The efficacy of pazopanib in patients (pts) who have progressed on other anti-angiogenesis agents, particularly sunitinib, is unclear. Methods: Pts with metastatic clear-cell RCC who had progressed on or were intolerant of first-line single-agent sunitinib or bevacizumab were eligible. Additional criteria: ECOG PS 0 or 1; measurable disease (RECIST); previous nephrectomy unless clinically inappropriate; no active CNS metastases; adequate bone marrow, kidney, liver function; no risk factors for anti-angiogenesis agents; informed consent. All pts received pazopanib 800mg PO daily. Response was assessed every 8 weeks until progression. Results: 44 pts have been treated with pazopanib (previous sunitinib – 32; previous bevacizumab – 12). Additional pt characteristics: male/female, 77%/23%; Motzer risk low/intermediate/high, 25%/43%/32%; previous nephrectomy, 93%. The median duration of treatment was 24 weeks (range 0 to 52 weeks). After a median follow-up of 9 months, efficacy is as follows (see table). 37 pts remain alive, and 13 are continuing treatment. Toxicity with pazopanib was similar to previous reports: frequent grade 3/4 toxicity included fatigue (14%), hypertension (11%), proteinuria (11%). Three pts discontinued treatment due to toxicity, and 13 required dose reductions. Conclusions: Pazopanib is active and well tolerated following treatment with either sunitinib or bevacizumab. All (N=44) Previous sunitinib (N=32) Previous bevacizumab (N=12) ORR 9 (20%) 5 (16%) 4 (33%) Disease control rate (CR+PR+SD) 31 (77%) 21 (66%) 10 (83%) Median PFS, mo. 9.23 (95% CI: 5.42, NA) 12.06 (95% CI: 6.14, NA) 8.05 (95% CI: 2.76, 11.93)
Prognostic significance of human epidermal growth factor-2 (HER2) in advanced gastric cancer: A U.S. and European international collaborative analysis.
Authors: M. A. Shah, Y. Y. Janjigian, C. Pauligk, D. Werner, D. P. Kelsen, E. Jaeger, H. Altmannsberger, E. Robinson, L. H. Tang, V. V. Barbashina, S. Al-Batran
Journal: Journal of Clinical Oncology (2011)

4014 Background: HER2 is a valid therapeutic target in advanced gastric cancer, however the prognostic significance of HER2 in this disease remains unknown. This analysis was performed to evaluate the prognostic significance of HER2 gene amplification or protein overexpression (HER2+) in advanced gastric cancer. Methods: Paraffin-embedded tumor samples of gastric cancer pts from six prospective first-line therapeutic trials of chemotherapy without trastuzumab performed in the U.S. and Europe were examined for HER2 by immunohistochemistry (IHC, 4B5) and in situ hybridization ISH (FISH or HER2 Dual ISH). HER2 positive disease (HER2+) was defined as IHC 3+ or ISH+ (ISH >2.0 HER2:CEP17FISH or HER2 Dual ISH). The impact of HER2 status was correlated with pt outcome using univariate and multivariate analysis. Results: 338 pts were evaluated: age 64 (28-88), M/F 233/105, GEJ/gastric 132/156, PS 0-1 224, Intestinal/Diffuse 125/140. 20.4% of all pts are HER2+. There were significant differences in HER2+ rates according to histological type (intestinal/mixed, 29%; diffuse, 8%; p<0.001), sex (M, 25%; F, 11%; p=0.012), and ECOG PS (0-1, 22%; 2-3, 10%; p<0.001). Similar rates of HER2+ tumors were found in biopsies vs. resections (22% vs. 19%) and in primary tumors vs. metastases (21% vs. 16%). Median overall survival was significantly longer in HER2+ pts (13.4 vs. 11.6 mos, HR 0.74; p=0.048) on univariate analysis. This prognostic value disappeared in multivariate analysis (p=0.3). In addition, HER2+ disease was not prognostic in subgroup analysis based on tumor histology. Factors associated with favorable survival in the multivariate analysis were intestinal type, female sex, recurrent disease, and ECOG PS 0-1. Conclusions: Approximately 20% of Western patients with advanced gastric cancer are HER2+. Although on univariate analysis, HER2+ was associated with improved overall survival, this was not independent of other known prognostic variables. Unlike breast cancer where HER2+ disease carries an adverse prognostic value, HER2+ disease is not an independent prognostic factor for pt outcome in advanced gastric cancer.
Experience with nipple-sparing mastectomy after prior whole-breast radiation.
Authors: Aimee Marlena Mackey, Bret Taback, Preya Ananthakrishnan, Sheldon M. Feldman
Journal: Journal of Clinical Oncology (2012)

173 Background: Nipple-sparing mastectomy (NSM) is being performed more frequently for risk reduction and breast cancer treatment. Prior whole breast irradiation (WBI) has been considered a contraindication to NSM. This study reviews our NSM experience following prior WBI. Methods: We reviewed our prospective mastectomy database from April 2007 to April 2012 for patients undergoing NSM. Ten patients out of a total 169 NSM were identified that underwent NSM following prior WBI. Data collected included incision type, follow-up, complications, cosmesis, and recurrence. Results: Of the ten NSM patients who received prior WBI, 6 had recurrent ipsilateral breast cancer at the lumpectomy site, 3 developed contralateral breast cancers and opted for bilateral NSM, and 1 patient opted for bilateral NSM after finding a BRCA mutation following BCT. Mean patient age was 53. Two patients had comorbities: 1 hyperlipidemia and 1 former smoker. Three of 10 (30%) developed complications, with 2 partial necrosis of nipple-areola complex (NAC) and 1 complete loss of the NAC (Table). No patient required return to the operating room (local resection in the office was performed for the complete NAC loss) and all patients had good final cosmesis. All patients underwent immediate reconstruction: 5 tissue expanders (TE), 2 DIEP and 3 TRAM flaps. Mean follow up is 23 months with no local recurrences to date. Conclusions: This study demonstrates that NSM with immediate reconstruction can be performed in selected patients with prior WBI with an acceptable rate of nipple preservation and good cosmesis. NAC preservation is the ultimate goal in patients undergoing NSM. Current studies are ongoing to identify risk factors that may be associated with nipple necrosis. [Table: see text]