tbuckley/cabot-search huggingface dataset:
Effect of PSA-tricom, a pox-viral vaccine in prostate cancer (PCa), on tumor growth rates within 80 days after initiation in nonmetastatic PCa.
Authors: James L. Gulley, Ravi Amrit Madan, Wilfred Donald Stein, Julia Wilkerson, William L. Dahut, Christopher Ryan Heery, Jeffrey Schlom, George Wilding, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2013)

57 Background: Our understanding of immunotherapies for prostate cancer (PSA-TRICOM, sipuleucel-T, ipilimumab) is incomplete in that such therapies have improved overall survival (OS) without changes in time to progression (TTP) in randomized trials. In an effort to better understand this discrepancy, we evaluated data from studies of PSA-TRICOM. A pox viral vaccine expressing PSA and 3 T-cell co-stimulatory molecules, PSA-TRICOM has demonstrated PSA-specific immune responses and evidence of clinical activity that supported initiation of a currently accruing Phase III trial. An analysis of NCI PCa trials (including a PSA-TRICOM trial) suggests that immune therapies may eventually slow the growth rate (GR) of tumors, leading to unaltered short term TTP, yet improved OS (Stein et al. Clin Can Res. 2011). Methods: PSA-TRICOM was administered to 50 hormone-naïve patients (pts.) with non-metastatic, castration naive PCa in a multi-center trial (ECOG 9802). Pts were treated every 4 weeks for 3 months, then every 12 weeks (preliminary data previously reported, DiPaola, RS et al. ASCO GU 2009). PSA values were used to calculate tumor GR within the first 100 days of treatment. (Pts were given no additional therapies during this time.) As previously described, a two-phase mathematical equation yielded concomitant PSA GR and regression rate constants.(Stein et. al., 2011) Results: See Table. Conclusions: These data suggest that PSA-TRICOM can alter GR significantly within 3 months. If confirmed in future trials, it could explain why vaccines have demonstrated improved OS without improved TTP. A slowing of the GR may not lead to substantial differences in short term TTP, but may enhance OS in the long term. This concept will be evaluated in an international Phase III trial of PSA-TRICOM in minimally symptomatic, metastatic castration-resistant PCa that is currently recruiting pts. Clinical trial information: NCT00108732. [Table: see text]
Final results of a phase II study of everolimus (RAD001) in metastatic transitional cell carcinoma (TCC) of the urothelium.
Authors: M. I. Milowsky, A. M. Regazzi, I. R. Garcia-Grossman, A. Trout, A. Flaherty, S. Gerst, H. Al-Ahmadie, I. Ostrovnaya, D. F. Bajorin
Journal: Journal of Clinical Oncology (2011)

4606 Background: Second-line chemotherapy has limited activity in advanced TCC with a median progression free survival (PFS) of 2-3 months. We have previously demonstrated the over-expression of activated mTOR pathway markers in invasive TCC specimens (BJU Int. 2010 Jul 26). Everolimus selectively inhibits mTOR, a central regulator of cell growth, proliferation, survival, and angiogenesis. This trial was designed to assess the efficacy of everolimus in patients (pts) with advanced TCC. Methods: The primary objectives of this single institution phase II trial of everolimus in pts with TCC who have failed prior chemotherapy are: 1) to measure PFS as determined by RECIST; and 2) to evaluate toxicity. Prior therapy is restricted to ≤ 4 chemotherapy drugs. Pts receive everolimus 10 mg oral daily continuously (1 cycle = 4 weeks). A Simon 2-stage design requires ≥13 of 23 pts to be progression free at 2 months to proceed to maximal accrual of 37. Results: 45 pts (31 M, 14 F) with a median age of 66 yrs (32-84) and median KPS of 90 (70-100) were enrolled between 02/17/2009 and 11/8/2010. Primary tumor sites include bladder (32 pts) and ureter/renal pelvis (13 pts). Prior therapy included 30 pts with 2 drugs, 13 with 3, and 2 with 4. 36 pts have visceral metastases including lung (23), liver (19), and bone (6), and 9 pts have lymph node only disease. The median PFS for 37 evaluable pts is 3.3 months (95% CI 2.1, 3.7). 2 partial responses in nodal metastases have been seen. The median OS for the 37 evaluable pts is 10.5 months (95% CI 7.8, NR). The most common grade 3-4 toxicities at least possibly related to everolimus include: anemia (7), infection (6), hyperglycemia (5), lymphopenia (4), hypophosphatemia (4), fatigue (4), hyponatremia (3), mucositis (3), dehydration (2), renal (2), and liver (2). Conclusions: Everolimus has clinical activity in pts with advanced TCC. An analysis of pre-treatment tumor tissue specimens for markers of activated mTOR pathway correlated with PFS will be presented.
Expression of PI3K/p-AKT/p-mTOR in gastric carcinoma and its correlation with clinicopathologic characteristics.
Authors: Ying Jieer, Xu Qi, Liu Bixia, Cheng Xiangdong
Journal: Journal of Clinical Oncology (2014)

73 Background: The objective of this study was to explore the expression patterns of PI3K/p-AKT/p-mTOR in gastric cancer (GC) and its relationship with clinicopathological characteristics and thereby to understand the role of activated PI3K/AKT/mTOR pathway in the initiation and development of gastric cancer. Methods: Envision immunohistochemistry assay was used to examine the expression patterns of PI3K, p-AKT and p-mTOR in primary GC sites, metastatic lymph nodes and peritumoral mucosa among 50 patients who underwent radical gastrectomy for stage I-IV (M0) gastric cancer. Results: The PI3K, p-AKT and p-mTOR showed significantly higher expressions in primary tumor sites and metastatic lymph nodes as compared to that of the peritumoral mucosa. The study of the pathway components and clinicopathological characteristics revealed that p-AKT and p-mTOR expressions were selectively higher in primary tumors with less than 5 cm diameter. The PI3K, p-AKT and p-mTOR positive patients had shorter median survival time as compared to the patients negative for them (42.8 m vs. 57.0 m, 46.8 m vs. 55.9 m, 47.2 m vs. 53.0 m). However, the differences were not statistically significant. Conclusions: Activation of PI3K/AKT/mTOR pathway was associated with the development and prognosis of gastric cancer. The expression of PI3K/p-AKT/p-mTOR was correlated well with tumor specificity in gastric cancer and they might have some potential as promising targets for clinical therapy.
Study of liposomal doxorubicin (LD) and oxaloplatin (OX) in pre-treated epithelial ovarian cancer (EOC)
Authors: M. O. Nicoletto, C. Falci, G. Crepaldi, P. Azzoni, E. Ferrazzi, G. Artioli, M. Donach, A. Perin, G. Nardelli
Journal: Journal of Clinical Oncology (2005)

5072 Background: Preclinical data show excellent synergy (1.15) between LD and Ox in ovarian cancer when given sequentially within 24 hrs, despite platinum resistance (Zoli, IOR Forlì, Italy). The aim of this phase II study is to evaluate the feasibility and efficacy of LD+Ox in pre-treated EOC. Methods: Inclusion criteria were: PS≤2, relapse or progression of disease after 1–3 lines of therapy, not including anthracyclins; ≤4 prior antiblastic drugs; life expectancy >3 months; LVEF >54%.Treatment consisted of 1 hr infusion of LD 30–35 mg/m2 on day 1 and 70 mg/m2 of Ox oin 2 hrs on day 2 for 8 cycles, followed by 2 cycles of LD alone. LVEF was monitored after 3, 6, and 9 cycles; clinical response was evaluated by Ecography, CT scan or MRI every 3 cycles. Results: Beginning June 2000, 40 pre-treated pts, 26 platinum-sensitive (pt-sens), [time to progression after 1st-line therapy >6 months] and 14 platinum-resistant (pt-res), were studied. Median age = 64 yrs, range 42–84, (16 pts >70 yrs). 25/40 pts had serous-papillary histology, 6/40 undifferentiated; 24/40 had grade III histology. 19/40 pts had multiple relapse sites. 248 cyckes were administered (median = 6 cycles/pt). In 11 pts chemotherapy was delayed because of neutropenia, paracentesis or concomitant problems. 3 pts had dose reduction of 60–90%.Major (G3–4) toxicities were: neutropenia (3 pts), gastrointestinal (1 pt).G1–2 neurosensorial toxicity was seen in 11 pts and PPE in 6 pts. Median LVEF showed no siginificant changes during treatment. 37 pts were evaluable for response. In 23 pts-sens, we obtained 7 CR (30.4%) and 8 PR (34.8%) (ORR=65.2%). 14 pts-res, 2 CR (14.3%) and 3 PR (21.4%) were recorded, with ORR=35.7%. Median survival by time-to-relapse was 10.6 months and 6.4 months in pt-sens and pt-res groups respectively (p=0.163). Time to progression was 7 months in pt-sens vs 6 months in pt-res (p=0.285). Conclusions: The value of this 2nd-line therapy and its impact on survival and quality of life is promising. No significant financial relationships to disclose.
The BCL-2-Specific BH3-Mimetic ABT-199 (GDC-0199) Is Active and Well-Tolerated in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Interim Results of a Phase I First-in-Human Study
Authors: John F. Seymour, Matthew S. Davids, Mary Ann Anderson, Thomas J. Kipps, William G. Wierda, John M. Pagel, Brad S. Kahl, Thomas P. Miller, David E. Darden, Cathy E. Nolan, Lori A. Gressick, Hao Xiong, David C.S. Huang, Brenda J. Chyla, Todd A. Busman, Alison M. Graham, Elisa Cerri, Sari H. Enschede, Rod A. Humerickhouse, Andrew W. Roberts
Journal: Blood (2012)
Community experience with a cancer survivor smoking cessation program.
Authors: Mark Allen O'Rourke, Stephanie Hoopes, Regina A Franco, Julie Frances Summey, Rachel Mayo
Journal: Journal of Clinical Oncology (2016)

182 Background: In 2014, GHS began a smoking cessation program for cancer survivors staffed by nurse practitioners and nurse navigators who are certified smoking cessation providers. The program is four scripted visits plus telephone support. Patients learn to become smoke-free by nicotine weaning and replacement, medication management, and integrative coping skills such as hypnosis. The purpose of this descriptive analysis is 1) to determine program smoking cessation rates and 2) to profile patients who completed the program successfully (nonsmoker status). Methods: Patient records from the first 12 months were mined for the following variables: demographics, primary insurance type, primary diagnosis, number of visits, number of cigarettes smoked per day at enrollment, alcohol use, and depression. Data was analyzed using Stata13. The GHS IRB approved the study. Results: Of the 143 patients referred to CIOS for smoking cessation during the first year, 70 (49%) enrolled in the program. 29 (20%) patients completed the program, and 11 (8%) others are in the process of completing the program. 23 (79%) of the 29 completers achieved non-smoker status at the time of program completion. Two months after program completion, only two nonsmoking completers reverted to smoking status. When stratifying completers by key demographic, clinical, and behavioral characteristics, the most successful were females (93% vs. 67% for males), Caucasians (82% vs. 71% for African-Americans), married individuals (100% success rate for married vs. 50% for divorced), and those with private insurance (100% vs. 79% Medicare and 67% Medicaid). Logistic regression did not reveal an increased probability of smoking cessation success with any of the key independent variables. Conclusions: This smoking cessation program using nicotine weaning and replacement, medication management, and integrative coping skills in a cancer survivor population has an encouraging success rate for those who complete the four-visit program. The relative success of married persons and females warrants further study as do the low enrollment rate of those referred, the low completion rate of those enrolled, and the continuing nonsmoking success rates for completers.
Survival in gastric cancer: A population-based cancer registry among residents in Shanghai, China.
Authors: C. Wu, P. Bao, Y. Zheng, K. Gu, C. Wang, Z. Huang, P. Peng, Y. Gong, Y. Xiang, W. Dong, W. Lu
Journal: Journal of Clinical Oncology (2011)

e12014 Background: Gastric cancer (GC) is one of the leading cancers both in terms of incidence and mortality in China. No large population-based epidemiological study of clinical characteristics and survival of GC has been reported in China. Methods: The data for this study were derived from the Shanghai Cancer Registry, compiled by the Shanghai Center for Disease Control and Prevention (Shanghai CDC). Consecutive, non-selected patients diagnosed with GC between January 1, 2002 and December 31, 2003 were included in the analyses. All newly diagnosed GC patients in any hospital in Shanghai were encouraged to participate in this registry and fill in a registry form. All registered cases were followed by the surveillance network of Shanghai CDC. Reports of deaths from hospitals, living status from the community, or loss to follow-up were updated through December 31, 2009. Cancer was staged using the International Union Against Cancer (UICC) version 6. Frequency and overall survival were examined. Results: 10 909 gastric cancer cases (male 64.5%, female 35.5%) were included in the study with a median age of 69 years. Stage was unknown for 6366 cases (58.4%); 5.5%, 9.9%, 12.4% and 13.8% were stage I to stage IV, respectively. For anatomic location of the tumor, 12.6% of cases were located in cardia, 43.5% were in non-cardia, while a large proportion of cases (44.0%) were unknown. There was no substantial difference in 5-year survival between men and women (25.3% vs. 27.5%, P= 0.18). However, 5-year survival rates varied significantly by tumor stage (67.5% in stage I, 48.5% in stage II, 26.5% in stage III, 7.5% in stage IV, and 22.7% in unknown staging cases, P<0.001). This was also true of anatomic location (18.8% at cardia, 33.6% at non-cardia, 20.7% at unknown status cases, P<0.001). Conclusions: Results from this large population-based registry indicate that treatment of GC in Shanghai may be challenging due to considerable late diagnosis and comparatively poor prognosis. Early detection and diagnosis should be encouraged.
Clinical outcomes and survival of patients (pts) with sarcomatoid metastatic renal cell carcinoma (smRCC).
Authors: Srinivas Kiran Tantravahi, David D. Stenehjem, Archana Agarwal, Sri Lakshmi S. Kollepara, Julia Anne Batten, Michael Ward, Dan Albertson, Junfeng Wang, Ting Liu, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2014)

535 Background: SmRCC is a rare variant of RCC associated with poor outcome. No definitive therapeutic recommendations exist. We present survival outcomes in pts with smRCC treated with systemic therapy. Methods: From a single institutional database (years 2000-2012), we identified 21 pts with documented sarcomatoid features who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, and Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria. Sarcomatoid component of the tumor was classified by predominant (≥20%) and non-predominant (&lt;20%). Immunohistochemistry (IHC) analysis was performed for mammalian target of rapamycin (mTOR) signaling, phosphorylated ribosomal protein S6, proviral integration site proteins (PIM 1,2,3), Beta-catenin, E-cadherin, phosphatase and tensin homolog (PTEN), U3 small nucleolar ribonucleoprotein (IMP-3), p53, and epithelial membrane antigen (EMA) on tumor samples, where available. Results: 21 pts were included with a median age of 62 years (range 39-74) and 13 pts were male (62%). One pt received first line cytotoxic chemotherapy, 3 pts received first line immunotherapy, and 17 pts received targeted therapy. Pts belonged to the following MSKCC risk categories: 1 (5%) favorable, 13 (62%) intermediate and 7 (33%) poor risk. Median overall survival (OS) of the entire cohort was 249 days (95% CI 161-519 days). Median OS in pts stratified as MSKCC poor, intermediate, and good risk was 2556, 430, and 137 days respectively (Poor vs Intermediate HR 4.38, p = 0.0159, CI 1.30-19.90). There was no significant difference in OS in pts with sarcomatoid predominant disease vs. non-predominant disease (234 vs 286 days, p = 0.744, HR 0.85, CI 0.31-2.39). Conclusions: Overall OS in pts with smRCC is inferior compared to that reported in clear cell variant mRCC. Although MSKCC risk scores may be useful in determining prognosis, further studies are needed to identify relevant biomarkers and define the optimal therapeutic strategy for this disease. Correlation of survival outcomes with the IHC profile of tumors will be presented.
Doubling of 30-day mortality by 90 days after esophagectomy: A measure of outcomes for quality improvement.
Authors: Haejin In, Bryan E. Palis, Mitchell Posner, Mark K. Ferguson, David P Winchester, Christopher M Pezzi
Journal: Journal of Clinical Oncology (2015)

134 Background: Delivery of high-quality cancer care critically relies on the ability to measure and compare quality for continuous improvement. For esophageal cancer, operative mortality has traditionally been assessed at 30 days. Ninety-day mortality has been suggested as a more appropriate indicator of quality particularly after complex cancer surgery. Our objectives were to: 1) compare 30- and 90-day mortality rates after esophagectomy; 2) compare drivers of 30- and 90-day mortality; and 3) examine whether 90-day mortality affects hospital rankings. Methods: Esophagectomies for non-metastatic esophageal cancer patients diagnosed between 2007 and 2011 were identified in the National Cancer Data Base (NCDB). Mortality rates were examined by patient demographics, tumor characteristics and hospital procedural volume. Risk-adjusted hierarchical logistic regression models examined hospital performance for mortality. Results: 15,805 esophagectomy patients at 977 hospitals were available for analysis. Ninety-day overall mortality was more than double the 30-day mortality (8.9% vs 4.2%, p&lt;0.0001). In multivariate analysis, while both 30- and 90-day mortality were associated with patient factors such as age, comorbidity and hospital volume, only 90-day mortality was influenced by tumor and management related variables such as stage, tumor location and receipt of neoadjuvant therapy. Hospital performance was examined as top 10%, middle 10-90% and lowest 10% as ranked using risk-adjusted odds of mortality. There was moderate correlation between ranking based on 30- and 90-day mortality [weighted kappa = 0.45 (95% CI 0.39 - 0.52)]. Compared to 30-day mortality rankings, nearly 20% of hospitals changed their ranking category when 90-day mortality rankings were used. Conclusions: Ninety-day mortality provides additional information for surgical risk assessment and has the potential to greatly enhance data for quality improvement efforts. Data provided for hospital quality improvement should include 90-day mortality, along with 30-day mortality and annual volume.
A randomized, phase II study of high-risk colorectal cancer patients (stage IIIC) treated with either regorafenib or standard of care (no treatment) after adjuvant FOLFOX.
Authors: Thomas H. Cartwright, Allen Lee Cohn, Donald A. Richards
Journal: Journal of Clinical Oncology (2016)

TPS779 Background: Standard adjuvant treatment for colorectal cancer (CRC) is usually a fluoropyrimidine or FOLFOX. However the relapse rate for stage IIIC patients is high with a median 5 year survival of only 28%. The multi-kinase inhibitor regorafenib has been shown to significantly improve progression-free and overall survival (PFS; OS) compared with placebo as 3 rd -line or later therapy for patients with metastatic CRC. Thus it is of interest to explore whether adding regorafenib to standard adjuvant therapy may be able to reduce the high relapse rates in patients with stage IIIC CRC. In addition, texture analysis (spatial variations in pixel intensity) of computed tomography (CT) scans may be a useful prognostic tool for determining risk of recurrence. Methods: The current study is designed to compare the efficacy and safety of adding 6 cycles of regorafenib versus standard of care (no additional systemic therapy) following 6 months of adjuvant FOLFOX in patients with high risk (stage IIIC) CRC. The primary endpoint is to find the starting dose of regorafenib that allows ≥ 75% of patients to complete therapy at the full dose following adjuvant FOLFOX. Secondary endpoints include estimation of disease-free survival (DFS) and OS, assessment of adverse events, and identification of associations between texture analysis results and DFS. The study will enroll 264 adult patients with stage IIIC CRC with no evidence of disease by CT scan after completion of 6 months of adjuvant FOLFOX therapy. The first 50 patients will be randomized to a starting dose of either 120 mg or 160 mg of regorafenib daily for 3 weeks followed by 1 week rest for a total of 6 cycles. Safety analyses will be performed after the first 26 patients complete 3 cycles of study treatment and again after 50 patients. Based on this determination, the remaining 214 patients will be randomly assigned (2:3) to receive 6 cycles of regorafenib at the selected starting dose or standard of care (no additional treatment). CT scans will be sent for texture image analysis and results correlated with DFS. Clinical trial information: NCT02425683. Clinical trial information: NCT02425683.
Pre-<sup>90</sup>Y hepatic radiotherapy hemoglobin and liver functions to predict overall survival in unresectable, chemotherapy-refractory metastatic colorectal cancer.
Authors: Andrew S. Kennedy, David Ball, Steven J. Cohen, Michael Cohn, Douglas M. Coldwell, Alain Drooz, Edward Ehrenwald, Samir Kanani, Fred M Moeslein, Charles W. Nutting, Samuel G. Putnam, Steven C. Rose, Michael Savin, Sabine Schirm, Navesh K Sharma, Eric Wang
Journal: Journal of Clinical Oncology (2014)

292 Background: Patients with liver metastases from colorectal cancers (mCRC) can benefit from 90 Y resin microsphere radioembolization (RE) administered via the hepatic arteries. This study investigated which standard laboratory tests may assist in improving treatment outcomes by identifying potentially correctable pre-radiation abnormalities prior to delivery of RE. Methods: A database containing retrospective review of 606 mCRC patients treated consecutively from July 2002 to December 2011 at 11 US institutions was used. Data collected included background characteristics, prior chemotherapy, surgery/ablation, radiotherapy, vascular procedures, 90 Y treatment, subsequent adverse events and survival. Kaplan-Meier estimates compared survival of patients across lines (0–≥4) of chemotherapy. The following values were obtained within 10 days prior to treatment: hemoglobin, albumin, alkaline phosphatase, AST, ALT, total bilirubin and creatinine. CTCAE v3.0 grade was assigned to each parameter and analyzed for impact on survival by line of chemotherapy. Where applicable, Consensus Guidelines were used to establish the abnormal limits for RE. Results: 606 patients (370 Male; 236 Female) were studied with a median follow-up of 8.5 months (IQR 4.3–15.6) after RE. Fewer than 11% of patients were treated outside recommended guidelines, with grade 2 albumin (&lt;3–2.0 g/dL) being the most common (10.5%) at time of RE. Abnormal parameters (grade &gt;0) were associated with statistically significantly decreased median survivals (p&lt;0.05) and this was consistent across most lines of prior chemotherapy. Compared to patients with grade 0, those with grade 2 albumin decreased median survival by 67%; for grade 2 total bilirubin, by 63%; and grade 1 hemoglobin, by 66%. Conclusions: Review of pre-RE laboratory parameters may aid in improving median survivals if correctable grade &gt;0 values are addressed prior to radiation delivery. Hemoglobin &lt;10 g/dL is a well-known negative factor in radiation response and is easily corrected. Improving other parameters is more challenging. These efforts are important in optimizing treatment response to liver radiotherapy.