tbuckley/cabot-search huggingface dataset:
SYNERGY: A randomized phase III study comparing first-line docetaxel/prednisone to docetaxel/prednisone plus custirsen in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: K. N. Chi, J. S. De Bono, C. S. Higano
Journal: Journal of Clinical Oncology (2011)

TPS180 Background: Custirsen (OGX-011) is a second generation antisense oligonucleotide (ASO) with a prolonged tissue half-life, greater potency and less toxicity than first-generation ASOs (CCR, 2008; 14(3): 833-839). Custirsen inhibits the expression of clusterin, a stress-induced, cytoprotective chaperone protein that is up-regulated in various cancers. In prostate cancer, clusterin expression is increased after androgen ablation or chemotherapy and contributes to treatment resistance. In vitro and in vivo studies show that the targeted knockdown of clusterin by custirsen results in increased sensitivity to cancer therapies (CCR, 2010; 16(4):1088-93). In a phase I neoadjuvant study, custirsen concentrations achieved in prostate tissue at the 640 mg dose level resulted in >94% decreases in clusterin expression and increased apoptosis (JNCI, 2005; 97(17): 1287-1296). Phase II studies have been completed in mCRPC, breast and lung cancer. In one phase II study, 82 patients with mCRPC randomized to receive docetaxel/prednisone (DOC/P) alone or DOC/P plus custirsen (640 mg IV weekly), median overall survival (OS) was 16.9 and 23.8 months in the two groups respectively, at a median follow-up of 35 months (JCO, 2010, 28:4247-4254). The phase III study, SYNERGY, will confirm whether adding custirsen to standard 1st line DOC/P treatment slows tumor progression and enhances survival beyond DOC/P alone. Methods: SYNERGY is a randomized, open-label, multi-center, international trial that is planned to enroll 800 patients with mCRPC. Chemotherapy-naïve patients will receive either DOC/P q 21d or DOC/P plus custirsen (640 mg IV weekly) until disease progression or unacceptable toxicity. The primary outcome measure is OS. Additional analyses include progression-free survival at Day 140 and Day 225, safety of custirsen combined with DOC/P, PSA measurements, and the association of efficacy measures with reduction of serum clusterin levels. All randomized patients will be included in the primary and secondary analyses (intent-to-treat analysis). The study was initiated in Sept, 2010 with an expected full accrual within 2 years. NCT01188187.
Influence of the localization of the primary tumor in the survival of patients with metastatic colon-rectal cancer treated with bevacizumab.
Authors: Inmaculada Gallego Jimenez, Amelia Lopez Ladron, David Morales Pancorbo, Eva Fernandez Parra, Maria Rodriguez de la Borbolla, Jose Fuentes Pradera, Reyes Bernabe Caro, Javier Salvador Bofill
Journal: Journal of Clinical Oncology (2014)

665 Background: Bevacizumab, a humanized antibody against the molecular target endotelial growth factor VEGF-A, has incorporated to the standard of care of metastatic colon-rectal cancer (mCRC). A recent study has suggested that the left colon localization of the primary tumor may be a factor associated with a poorer survival in individuals treated against mCRC with bevacizumab including chemotherapy. Our objective was to analyze the impact of the localization of the primary tumor on the survival of patients with mCRC treated with bevacizumab. Methods: Prospective cohort study conducted in a tertiary-care hospital in Spain. Twenty-nine consecutive patients with mCRC who started a first-line therapy including bevacizumab were included. Patients were followed up until death, lost to follow-up or the censoring date (31th August, 2013). The primary end-point of the study was death from any cause. Predictors of survival, including the localization of the primary tumor, were assessed. Results: The median (Q1-Q3) age was 59 (52-67) years and 13 (45%) patients were male. Chemotherapy scheme was XELOX in 13 (45%) patients, FOLFOX in 8 (28%), FOLFIRI in 5 (17%), XELIRI in 2 (7%) and capecitabine in 1 (3%) patient. The localization of the primary tumor were distributed as follows: rectum in 6 (21%), sigmoid colon in 9 (31%), left colon in 9 (31%) and right colon in 5 (17%) patients. After a median (Q1-Q3) follow-up of 29 (13-41) months, 19 (66%) patients died. There were no patients lost to the follow-up. The mean (SD) survival in patients with left colon cancer was 25 (8) months whereas it was 47 (7) months in the remaining population (p = 0.1). The low sample size precluded to perform reliable multivariate analyses. Conclusions: Our study suggests that left colon localization of the primary tumor may have a worse prognosis in patients with mCRC treated with bevacizumab. Although no statistically significant differences have been observed, this fact may have been a consequence of the limited power of the analysed sample. Collaborative studies should be perfomed in order to clarify this issue.
Review of trends in adjuvant chemotherapy regimens in breast cancer over 10 year period at Yale New Haven Hospital (YNHH).
Authors: Rosana Gnanajothy, Gina G. Chung, Michael DiGiovanna, Maysa M. Abu-Khalaf, Donald R. Lannin, Lyndsay Harris
Journal: Journal of Clinical Oncology (2015)

144 Background: Adjuvant chemotherapy for breast cancer has undergone many changes over the past 10 yrs. The objective of the study was to review prescribing trends in adjuvant chemotherapy regimens for early stage breast cancer in a single institution, over a decade. Methods: A retrospective chart review was conducted of patients (pts) with early stage breast cancer treated at YNHH from 2002 to 2011.Total charts analyzed was 1097 and 308 pts had complete data. Results: The HER 2 positive group accounted for 64 pts. The most commonly used regimen was ACTH (doxorubicin and cyclophosphamide 4-14 d cycles, paclitaxel and trastuzumab weekly for 12 weeks, and trastuzumab for 1 yr). This regimen was utilized in 35% of pts and was most likely to be used in node positive (N+ve) pts compared to node negative (N-ve) pts (OR 2.9 (95 % CI 0.97-9.1)).TCH (docetaxel, carboplatin, trastuzumab,6-21 d cycles and trastuzumab for 1 year) was the second most common regimen used in 21% of pts and predominantly in N-ve pts(OR 12.4 (95% CI 02.45-63.2)). Majority of the study group (184 pts) were ER+PR+ and HER 2- .The predominant chemo regimen was DD AC T (dose dense AC followed by paclitaxel in 4 -14d cycles each) in 50% of pts, and TC (Docetaxel, cyclophosphamide4-21d cycles) utilized in 48 pts (26.09 %). Majority of the N-ve pts were treated with TC (OR 12.4(95% CI 2.4-63.27) whereas N+ve pts were predominately treated with DDACT (OR 2.98(95% CI 0.97-9.16). The Triple negative group included a total of 57 pts .The most frequent chemo regimen through the years was DDACT (54.39% of pts) followed by TC (21.05% of pts). N+ve pts were more likely to be treated with DDACT (OR 8.91(95% CI (2.65-29.94)) whereas N-ve pts mostly received TC (OR 8.75(95% CI (1.70-45.00)) The methotrexate and 5 fluorouracil based regimens were utilized more frequently in earlier years of study and less frequently in later years. Conclusions: Anthracycline and taxane based regimens have gained precedence over older regimens. HER 2 +ve pts were most commonly treated with ACTH, and TCH. N+ve HER 2+ pts were most likely to be treated with ACTH and N-ve HER2+ pts with TCH. In Her 2 negative and triple negative pts, DDACT was more utilized in N+ve pts whereas, TC regimen in the N-ve pts.
Effect of previous abdominal surgery on short-term outcomes following laparoscopic colorectal surgery.
Authors: Masanori Hotchi, Yuhei Waki, Kazunori Tokuda, Masayoshi Obatake, Hiroshi Kotegawa, Hirotsugu Yoshiyama, Masamitsu Harada, Hideki Kawasaki
Journal: Journal of Clinical Oncology (2014)

653 Background: The impact of previous abdominal surgeries on the need for conversion to open surgery and on short-term outcomes during/after laparoscopic colorectal surgery was retrospectively investigated. This retrospective cohort study was conducted from May 2004 through October 2012. This study was conducted at Tokushima University Hospital and Ehime Prefectural Central Hospital. Methods: A total of 145 consecutive patients who had undergone laparoscopic resection of the sigmoid colon and upper rectum were classified as not having previous abdominal surgery (NPAS group, n = 123) or as having previous abdominal surgery (PAS group, n = 22). Short-term outcomes were assessed between the two groups. Results: The population of previous abdominal surgery consisted of 6 appendectomy, 3 gastrectomy for gastric ulcer, 2 nephrectomy, 2 peritonitis and 11 others (2 duplication). There were no significant differences in age, gender, BMI, tumor location, tumor size, Stage, operating time, blood loss and number of lymph node harvest between the two groups. The conversion to open surgery was performed in 1 patient (4.5%) in the PAS group and 6 patients (4.9%) in the NPAS group. The intraoperative inadvertent enterotomy occurred in 1 patient in the NPAS group. There was no difference in postoperative morbility between the two groups. In the NPAS group, anastomotic leakage was observed in 3 cases. Ileus was observed in one case in the NPAS and none in the PAS. Postoperative hospital stay was 14 days in the PAS group and 16 days in the NPAS group. Conclusions: Short-term outcomes following laparoscopic surgery for sigmoid colon and upper rectal cancer with previous abdominal surgery are acceptable.
Creation and implementation of a corporate compliance program (CCP): The Illinois CancerCare (ILCC) experience.
Authors: Bridgette Heard, Kendall Howard, Laura M. Miller, Pankaj Kumar
Journal: Journal of Clinical Oncology (2013)

256 Background: In 2000, Office of Inspector General (OIG) provided guidance for physician practices in the adoption of corporate compliance program (CCP). The notice provided a basic outline that would allow organizations to detect, prevent and possibly report potential fraud and abuse as it relates to federal health care payers. Insurance payers, e.g., United, Healthcare, and Humana, are also requiring organizations to institute CCP for reimbursement. As health care reform evolves there is will be a greater need for an alliance between providers and payers as each are increasingly held accountable for their actions related to ethical behavior in documentation, billing and coding, HIPAA, improper inducements, kickbacks, financial conflicts of interest, in addition to other areas. Methods: The Illinois CancerCare (ILCC) is one of the largest private oncology practice in Midwest. We implemented the components outlined by OIG by completing the following tasks: identifying and empowering a compliance officer; identifying high-risk areas; developing policies and standards for major processes that might lead to fraud, waste, or abuse; developing a training program for all physicians, NPs, and employees; creating and implementing an auditing and monitoring program; developing investigation and remediation standards; and establishing committees for oversight. Results: The entire process took 18 months to be fully functional. We have developed a plan that is completely complaint and meets all the criteria as required and our personnel have been trained. Conclusions: In future most large practices in the United States will likely be required to have a CCP. It is complicated and includes multistep processes. In the end, implementing a CCP allows organizations to show their desire to be a quality organization with internal monitors to ensure they are participating in federal health care programs using ethical standards.
Comparison of survival of African-American (AA) patients (pts) in docetaxel (D)-based combination therapies in metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Fatima Karzai, Ravi Amrit Madan, Yang-Min Ning, Marc Robert Theoret, Philip M. Arlen, Howard L. Parnes, Michelle A. Ojemuyiwa, Julius Strauss, Nancy Ann Dawson, David G. McLeod, Nancy Harold, Anna Couvillon, Lisa M Cordes, Clara Chen, Seth M. Steinberg, Tristan M. Sissung, Douglas K. Price, James L. Gulley, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2016)

272 Background: AA pts experience greater prostate cancer (PC) incidence and mortality compared to Caucasian (C) pts but are underrepresented in clinical trials (CTs). Greater representation of AAs is required to explore differences in clinical benefit in advanced disease where recent data has reaffirmed the role of D. Methods: In a retrospective analysis, baseline characteristics, Gleason score (GS), ECOG PS, number of cycles (cys), maximum prostate-specific antigen (PSA) declines, radiographic responses, overall survival (OS) and progression-free survival (PFS) were captured in 2 recent D based CTs. Results: Of 136 pts, 28 (21%) self-identified as Black or AA. Median age of AA pts is 66 (50-78 yrs). Median GS is 8 (5-10). Median ECOG PS is 1 (0-2). 15 pts have bone and soft tissue disease; 13 pts have bone only disease. Median number of cys is 28.5 (1-63). Of 27 evaluable pts, 26 had PSA declines (-26 to -99%). Radiographic responses include 11 (39%) partial responses and 16 (57%) pts with stable disease. Median OS for AAs is 29.0 months (mos) (95% CI: 20.9-34.7 mos); median PFS is 21.5 mos (95% CI: 13.7-28.9 mos). Median OS for all non-AA pts is 24.8 mos (95% CI: 21.8-29.5 mos); median PFS is 16.1 mos (95% CI: 14.1-20.1 mos). The VEGF-634G &gt; C SNP, associated with a more aggressive phenotype of PC, was evaluated in 54 pts. No evidence was found that genotype frequency varies between C and AA pts. Conclusions: In this analysis, AA pts did not have inferior OS (29 mos) or PFS (21.5 mos) outcomes compared to non-AA pts (24.8, 16.1 mos). Further analysis from larger studies is required to determine differential benefits of D for AA pts compared to non-AA pts. Clinical trial information: NCT00089609, NCT00942578.
Breast cancer patients with diabetes mellitus: Defining the population and assessing outcomes.
Authors: Nina J. Karlin, Amylou C. Dueck, Sravan K. Nagi Reddy, Patricia M. Verona, Curtiss B. Cook
Journal: Journal of Clinical Oncology (2013)

137 Background: Diabetes has been associated with an increased risk of mortality among patients with many types of cancers. Methods: We performed a case-control study of 109 breast cancer patients to determine the impact of diabetes on disease recurrence and survival. These 109 patients diagnosed with invasive breast cancer during 2007-2011 with diabetes were identified from the institutional Cancer Registry and matched to 109 breast cancer patients without diabetes according to age, race/ethnicity and year of diagnosis. Statistical tests included paired t-tests, McNemar’s tests, and stratified Cox regression. Results: The median ages of those with and without diabetes were 68 years, and 91% in both groups were white (both matched). Patients with and without diabetes were not significantly different in terms of tumor grade, cancer stage, estrogen or progesterone receptor status, HER2 neu status, marital and employment status, smoking use, use of adjuvant chemotherapy, and steroid treatment (all P &gt;.4). Patients with diabetes reported less use of alcohol (50% vs 64%, P=.04), and had greater BMI (79% overweight/obese vs 58%, P= .002). Survival analysis demonstrated no differences in survival from initial breast cancer diagnosis (HR=1.25, 95% CI 0.49-3.17) with median follow-up of 2.2 years (range 0.1-4.9), and no differences in recurrence-free survival (HR=1.00, 95% CI 0.14-7.10) though very few deaths and recurrences were observed. Within the diabetes group, 96 (88%) had type 2 diabetes and 97/106 (92%, 3 unknown) had diabetes pre-existing to cancer diagnosis. Initial diabetes therapy included diet (33, 30%), oral therapy (48, 44%), insulin (21, 19%), or oral+insulin (6, 6%). 7 patients required a change in diabetes therapy within 1 year of cancer diagnosis with 3 patients starting insulin. 32/70 (46%) with available lab data had 1 or more A1C &gt;/=7 within 1 year of cancer diagnosis. Conclusions: In this retrospective, carefully matched case-control study, we developed a comprehensive profile of the patient population with newly diagnosed breast cancer and diabetes. Diabetes did not appear to impact mortality or recurrence-free survival based on descriptive estimates in this small breast cancer cohort.
Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting (CINV) in U.S. community oncology practice: INSPIRE study.
Authors: James W. Gilmore, Nancy Walker Peacock, Anna Gu, Stephen Szabo, Melissa Rammage, Joyce Sharpe, Sally Haislip, Toni S. Perry, Tim Lee Boozan, Katherine Meador, Xiting Cao, Thomas A. Burke
Journal: Journal of Clinical Oncology (2012)

167 Background: Electronic Health Records (EHRs) are a valuable source to evaluate the quality of oncology care, particularly when combined with patient outcomes data. Our objective was to evaluate the impact of guideline consistent/inconsistent chemotherapy prophylaxis (GCCP, GICP) on the incidence of no CINV after cycle 1 of highly or moderately emetogenic chemotherapy (HEC or MEC). Methods: INSPIRE (Impact of NCCN Antiemesis Guideline Usage on Patient Reported Emesis) was a prospective observational, multicenter study that enrolled chemotherapy-naive adults initiating single-day HEC or MEC. Results from the MASCC Antiemesis Tool, administered 5 to 8 days after HEC/MEC, were merged with EHR data. The primary endpoint, no CINV (no emesis and no clinically significant nausea), was compared between groups using logistic regression. Results: 1,295 patients (mean age=59.3, 30.0% male, 35.5% HEC) were enrolled from Georgia Cancer Specialists (53.0%), Tennessee Oncology (38.1%), Florida Cancer Specialists (5.7%), and Cancer Specialists of N. Florida (3.2%). The prevalence of GCCP was 57.3% (28.7% HEC; 73.1% MEC). If corticosteroids were prescribed to all HEC patients on days 2-4, GCCP for HEC would increase from 28.7% to 89.8%. If NK1-receptor antagonists (NK1-RA) were prescribed to all MEC patients, GCCP for MEC would increase from 73.1% to 97.8%. GCCP and GICP-treated patients differed by age, (p=0.010), HEC/MEC (p&lt;0.0001), primary cancer site (p&lt;0.0001), practice site (p&lt;0.0001). The percent with no CINV, no emesis, and no clinically significant nausea was significantly higher for GCCP patients. Conclusions: Increased GCCP could significantly reduce CINV after HEC or MEC. The main reasons for guideline inconsisteny were lack of corticosteroids in the delayed phase for HEC and lack of NK1-RA for MEC. There remains room for improvement in nausea control. [Table: see text]
Proton reirradiation of locally recurrent pancreatic and ampullary adenocarcinomas.
Authors: John Peter Plastaras, Abigail Berman, Smith Apisarnthanarax, Stefan Both, Kristi Varillo, Gary L. Larson, Edgar Ben-Josef, James M. Metz
Journal: Journal of Clinical Oncology (2013)

317 Background: Local recurrences of pancreatic and ampullary cancer can be painful and cause significant morbidity. Their treatment after resection and chemoradiation is particularly challenging. A second course of radiotherapy (RT) in a previously radiated field carries the risk of RT-induced tissue injury. Proton therapy (PRT) may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 2/2011 and 8/2012, 10 adult patients (pts) with locally recurrent pancreatic or ampullary malignancies in or near prior treatment fields began reirradiation. Toxicity was graded according to the CTC v4.0. Acute toxicity was defined within 90 days from start of PRT. Results: Median follow-up was 8.2 months (1.1-19.1) from the start of retreatment and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 67 (54-75). Nine of the pts had pancreatic adenocarcinoma and 1 had ampullary adenocarcinoma. Median clinical target volume size was 86.4 cc (15-236). Nine received concurrent 5-fluorouracil or capecitabine-based chemotherapy. The median total dose was 59.4 Gy(RBE)(45-59.4); all pts were treated with PRT exclusively, except for one pt who was treated with 36% photon volumetric arc therapy. The median prior dose was 50.4 Gy (30-59.4). The median interval between RT courses was 34 months (17-461). Nine pts had Grade 2 and 1 had only Grade 1 non-hematologic acute toxicity. No Grade 2 or higher non-hematologic RT-related toxicities were observed after 90 days from the start of RT. Five pts developed metastatic disease at a median of 7.4 months (4.8-13.2) after starting RT, 1 of whom died at 5.3 months. One pt developed progressive regional (paraaortic) disease inferior to the fields while on treatment and was stopped early at 45 Gy. One pt developed a regional metastasis (porta hepatis) outside of the retreated volume. The other 8 pts were controlled locally within the retreated fields. Conclusions: Reirradiation of pancreatic/ampullary cancers with PRT and concurrent chemotherapy has minimal acute toxicity and encouraging short-term local control. Further follow-up on these pts is needed to assess the long-term morbidity and utility of PRT reirradiation. Clinical trial information: NCT01126476.
A pilot study of supraphysiologic testosterone (T) and oral etoposide (E) in men with castrate-resistant prostate cancer (CRPC).
Authors: Michael Thomas Schweizer, Emmanuel S. Antonarakis, Hao Wang, Avery N. Spitz, Haiyi Cao, Alberto Pacheco, Mario A. Eisenberger, Michael Anthony Carducci, Samuel R. Denmeade
Journal: Journal of Clinical Oncology (2014)

45 Background: Prostate cancer (PC) cells become resistant to chronic castration via an adaptive increase in androgen receptor (AR) expression, a liability that can be exploited therapeutically. Mechanistically, supraphysiologic androgens can induce PC cell death through topoisomerase 2 (topo2) mediated double-strand DNA breaks and disruption of DNA relicensing due to persistence of AR at origins of replication during the cell cycle. Methods: We evaluated parenteral T in combination with the topo2 inhibitor E in men with CRPC and low metastatic burden (≤5 bone and &lt;10 soft tissue metastases). To rapidly cycle from supraphysiologic (&gt;1500 ng/dL) to near castrate T levels, men received intramuscular T cypionate 400 mg on day (D) 1 and oral E 100 mg D 1-14 of a 28 D cycle. After 3 cycles, men with declining PSA could continue T alone every 28 D. The primary endpoint was PSA response, defined as a PSA below baseline, after cycle 3. Secondary endpoints included objective response rates and safety. Results: Sixteen men enrolled of which 14 completed 3 cycles of T+E and were evaluable for response. 7/14 went on the T-only expansion stage. After 3 cycles, 6/14 men had a PSA response. 7 (50%) had a PSA response at any timepoint [4 (29%) had PSA declines ≥50%] (table). In men with RECIST-evaluable disease, 2 had progressive and 3 had stable disease (SD), 4 had partial (PR) and 1 had a complete response (CR). Median response duration was 248 D (range, 80 to 359 D). Post T, 10/12 men had a PSA decline to subsequent androgen ablative therapies. Most adverse events (AEs) were ≤grade 2 and considered effects of E. One man died from neutropenic sepsis before completing the 1st cycle. AEs possibly related to T included lower extremity edema (n=1), priapism (n=1) and asymptomatic pulmonary embolism (n=2). No one developed new pain on T. Conclusions: T with or without E demonstrated preliminary efficacy in patients with CRPC as manifested by PSA and objective responses. This regimen is generally safe. Cyclic T-based therapies warrant further study. Clinical trial information: NCT01084759. [Table: see text]
Addition of Rituximab to BEACOPPescalated to Improve the Outcome of Early Interim PET Positive Advanced Stage Hodgkin Lymphoma Patients: Second Planned Interim Analysis of the HD18 Study.
Authors: Peter Borchmann, Heinz Haverkamp, Andreas Lohri, Stefanie Kreissl, Richard Greil, Jana Markova, Michaela Feuring-Buske, Julia Meissner, Ulrich Dührsen, Nicole Engel, Ulrich Keller, Georg Maschmeyer, Markus Dietlein, Carsten Kobe, Michael Fuchs, Volker Diehl, Andreas Engert
Journal: Blood (2014)