tbuckley/cabot-search huggingface dataset:
The association between statin use and outcomes in patients initiating androgen deprivation therapy.
Authors: Robert James Hamilton, Keyue Ding, Juanita M. Crook, Christopher J. O'Callaghan, Celestia S. Higano, David Dearnaley, Eric Horwitz, Larry Goldenberg, Mary K. Gospodarowicz, Laurence Klotz
Journal: Journal of Clinical Oncology (2015)

145 Background: Studies are conflicting regarding the association between statin use and biochemical recurrence after surgery or radiotherapy for localized prostate cancer. A handful of studies have observed favorable associations between statins and prostate cancer-specific (PCSM) and overall mortality (OS), however, this has not been studied in an advanced disease cohort nor has the combination of statins and androgen deprivation therapy (ADT) been specifically studied. Methods: Patients with PSA &gt;3 ng/mL after &gt;1 year following primary or salvage radiotherapy (RT) were enrolled in a randomized trial of intermittent (IAD) vs. continuous (CAD) ADT (NCT00003653). Statin use at baseline and during the study was captured and modeled as a time-dependent covariate. The primary end-point was OS. Models were adjusted for age, time from RT to ADT and PSA at baseline. As results were nearly identical between the IAD and CAD arms they are reported as aggregates unless otherwise indicated. Results: Of 1,364 patients enrolled, 585 (43%) reported statin use during the study. Statin users were younger (72.7 vs. 73.8, p=0.001) and less likely to have PSA &gt;15 (20 vs. 25%, p=0.04). Median follow-up was 6.9 years and 524 deaths occurred. Statin use was associated with a reduced risk of overall death (HR: 0.64; 95% C.I. 0.53 – 0.78, p&lt;0.001) and PCSM (HR: 0.64, 95% C.I. 0.48 – 0.86, p=0.003). Statin users had 14% longer time to castration resistance but this did not reach statistical significance (p=0.15). In the IAD arm, statin users had more off-treatment intervals (p=0.04) and longer time off-treatment (median: 0.85 vs. 0.64 years, p=0.06). Across 6 functional domains, statin users reported better quality of life scores. Conclusions: In men treated with ADT following primary or salvage RT, statin use was associated with improved overall and prostate cancer-specific survival and improved quality of life. In patients treated with IAD, statin use was associated with more off-treatment intervals and longer time off-treatment. A prospective trial of statins in men commencing ADT is warranted to confirm this observation.
Association of osteprotegerin, bone turnover, and bone loss after adjuvant chemotherapy in early-stage breast cancer.
Authors: Drew Randall Oostra, Maryam B. Lustberg, Xueliang Jeff Pan, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2013)

134 Background: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. RANK-RANK ligand (RANK-L) signaling is important in regulating osteoclast development and is essential in maintaining the balance between bone resorption and formation. Osteoprotegerin (OPG) is involved in RANK-RANKL signaling by acting as a decoy receptor for RANK and thus interrupting osteoclast activation and subsequent bone resorption. The objective of this study was to examine the relationship between OPG and bone health in women with early-stage breast cancer who develop CIOF. Methods: Premenopausal women with stage I and II breast cancers receiving adjuvant chemotherapy were evaluated, within 4 weeks of starting chemotherapy (baseline), at 6 months and at 12 months. They were evaluated with bone mineral density (BMD) at lumbar spine (LS), BMD at femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium (iCa), osteocalcin (OC) and osteoprotegerin (OPG) measurements. CIOF was defined as negative pregnancy test, 3 or more months of amenorrhea, and an FSH &gt;30 MIU/mL at the 12 month time point. Results: Forty women with stage I and II breast cancer receiving adjuvant were included in this analysis. Thirty-one (77.5%) were identified as having CIOF. In the CIOF group, there was statistically significant decreases in BMD (at the LS and FN) at both 6 months and 12 months (all P's &lt;0.001). The LS BMD decreased from 0.993 (0.935-1.123), to 0.976 (0.869-1.100) to 0.937 (0.834-1.062), at 6 and 12 months respectively (median and inter-quartile range). OPG was significantly increased at 6 months (median increase 0.30, P=0.015), and then went down at 12 months, but was still higher than baseline (although not statistically significant, median difference 0.2, p=0.70). Significant increases in OC were also noted at 6 and 12 months (both P&lt;0.001). Conclusions: In the CIOF group, OPG increases in the first 6 months in CIOF and at 12 months was slightly decreased but still remained elevated over baseline. This is likely due to a compensatory response to rapid bone loss. This compensatory response has been reported in other diseases, but not in CIOF.
Short-term outcomes of laparoscopic surgery after insertion of self-expandable metallic stent as a “bridge to surgery” for left-sided obstructive colorectal cancer.
Authors: Yuhei Waki, Kazunori Tokuda, Masayoshi Obatake, Miya Nagahashi, Masanori Hotchi, Hiroshi Kotegawa, Hirotsugu Yoshiyama, Masamitsu Harada, Hideki Kawasaki
Journal: Journal of Clinical Oncology (2014)

643 Background: Safety and validity of performing laparoscopic surgery after preoperative lavege using the self-expandable metallic stent (SEMS) for left-sided obstructive colorectal cancer were examined. We evaluated the short-term outcome of SEMS insertion compared with laparoscopic surgery without SEMS. Methods: Patients with left-sided colorectal cancer treated by either laparoscopic surgery with stent placement (n = 8) or laparoscopic surgery only (n = 42) in our hospital between April, 2012 and January, 2013 were registered. Short-term outcomes were compared with the two groups about patient characteristics (sex, age, American Society of Anesthesiologists Physical Status, body mass index, prior abdominal surgery), pathological data of patients (tumor location, size of tumor , tumor differentiation, number of harvested lymph nodes, pTNM classification, UICC pathological stage), and operative and post operative results (procedures, conversion, operative time, blood loss, morbidity, solid food intake, postoperative hospital stay, total hospital stay). Results: Except for tumor size in the patient characteristic parameters, there were no statistically significant difference between the two groups. Conversion rate to laparotomy was higher in the stent group (2 versus 1, p = 0.013). There was no difference in operation time, blood loss and postoperative complications between the two groups. Conclusions: Although the long-term oncological result requires further investigation, laparoscopic surgery after self-expandable metallic stent is a safe and feasible treatment as a “brige to surgery” for left-sided obstructive colorectal cancer.
Tumor contact length: A novel multiparametric MRI predictor of prostate cancer outcomes.
Authors: Michael Kongnyuy, Arvin Koruthu George, Amogh Iyer, Thomas P Frye, Amichai Kilchevsky, Abhinav Sidana, Spencer Krane, Meet Kadakia, Akhil Muthigi, Francesca Mertan, Raju Chelluri, Richard Ho, Daniel Su, Maria J Merino, Baris Turkbey, Peter L. Choyke, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2016)

61 Background: Multiparametric MRI (MP-MRI) can visualize prostate tumors. MP-MRI characteristics (extraprostatic extension (ECE), tumor volume, etc.) can be predictive of final pathologic findings such as lymph node (LN) involvement, pathological ECE (pECE), and biochemical recurrence (BCR). These are pivotal in the decision-making process regarding treatment. Tumor contact length (TCL) is defined as the length of cancer in contact with the prostatic capsule. We evaluated the ability of MP-MRI determined TCL in predicting pECE, BCR and LN in patients undergoing radical prostatectomy. Methods: All patients who underwent a 3T MP-MRI at the NCI from 2007 to 2015 were retrospectively classed into no ECE, suspicious ECE (sECE) and frank ECE (fECE) based on MP-MRI findings. sECE was defined as tumor with capsular bulge on MRI while fECE was clear capsular obliteration and tumor extension beyond the prostatic capsule. Demographic data was obtained on patients with fECE and sECE on MP-MRI with the presence of pECE, LN, and BCR status following radical prostatectomy from a single surgeon (PP) experience. Chi-Square and Wilcoxon rank sum test were used to compare proportions and continuous variables respectively. Logistic regression was used to determine the predictive ability of TCL. Statistical significance was defined as p-value ≤0.05. Results: Of all 1,260 patients who underwent MP-MRI, we focused on 146 who had sECE (68) or fECE (78) on MP-MRI. Mean age was 60 years and median prostate specific antigen was 11.7 ng/ml. Logistic regression analysis showed that MP-MRI determined TCL was predictive of ECE (p=0.01), LN status (p=0.0001) on final pathology and BCR (p=0.05) during follow up. Patients with pECE had a longer median MP-MRI TCL (2.8 cm) compared to those without pECE (2.4 cm), p=0.04. When analyzed individually, fECE correlated with pECE (p=0.05) while s ECE did not correlate with pECE (p=0.11). Although, not statistically significant, the median MP-MRI TCL for sECE with pECE was still longer than in sECE with no pECE in the sub-group analysis. Conclusions: Longer TCL on MP-MRI can indicate presence of ECE, LN involvement at final pathology as well as predict BCR on follow up.
Perspectives on palliative care in a multisite oncology practice.
Authors: Kenneth D. Bishop, Angela Marie Taber
Journal: Journal of Clinical Oncology (2014)

52 Background: The Institute of Medicine reported that many cancer patients do not receive palliative care to manage symptoms. It is possible that practitioners do not identify palliative care as an important component of high-quality cancer care, or do not know how to most efficiently utilize available palliative care consultative services. Methods: An anonymous electronic survey was sent to physicians, nurses, nurse practitioners, physician assistants, and social workers (n=99) in our multi-site, single-institution Cancer Center. Results: Sixty-five responses were received (66% response rate). Eighty-three percent of respondents reported working primarily in the outpatient setting. Fifty-nine percent reported their patients ‘rarely use the ER for pain management’ while 16% reported their patients ‘frequently require ER visits for pain management’. Ninety-two percent considered palliative care ‘an integral part of a multidisciplinary team’ while 6% reported palliative care consultation to be ‘cumbersome to consult and coordinate with’. The most common reason for consultation was end-of-life discussions (38%) followed by chronic pain management (33%). Seventy-seven percent reported consulting between 1 and 5 times per month, 14% between 6-10 times per month, and 5% greater than 11 times per month. Thirteen percent reported that they were able to manage patient symptoms adequately themselves. The average rating for convenience of consulting palliative care was 3.8/5. Fifty-eight percent reported the most effective means of communication with palliative care consultants was through the medical record, whereas 42% reported that most effective communication took place in person. Sixty percent reported a preference for palliative care practitioners from within the division of hematology/oncology. Conclusions: Our survey suggests that the majority of oncology practitioners value palliative care consultation and are willing to incorporate palliative care services into patient management. It is possible that practitioners overestimate their utilization of palliative care services and that optimizing the convenience of consultation and communication would result in better integration of palliative care for cancer patients.
The use of bevacizumab and concurrent radiation for recurrent gynecologic cancers.
Authors: A. N. Viswanathan, J. Szymonifka, C. Tanaka, S. T. Berlin, S. M. Campos, N. S. Horowitz, J. Lee, C. Whalen, U. Matulonis
Journal: Journal of Clinical Oncology (2011)

5101 Background: To determine the feasibility and preliminary efficacy in a pilot trial of concurrent bevacizumab (Bev) and external beam radiation (EB) for patients with recurrent (rec) gynecologic (gyn) malignancies. Methods: Twenty women were enrolled on a prospective IRB-approved pilot protocol between 2008 and 2010 at BWH/Dana-Farber Cancer Institute. Eligible patients (pts) had rec gyn cancer deemed amenable to EB to a confined area and had no or well-controlled hypertension and no recent vascular events. Standard protocol for these pts would have been EB alone. All pts received Bev 10mg/kg IV q2 weeks for 3 doses (days 1, 15 and 29 during radiation). EB was given daily in 1.8 Gy fractions to a dose of 45 Gy +/- nodal boost +/- brachytherapy. Toxicity (CTCAE version 3.0) was assessed at baseline, weekly during treatment and every 3 months for 1 year after treatment. Study-limiting toxicities (SLT) were defined as any grade 4 thrombotic/embolic/hemorrhagic or hypertensive event, bowel perforation or death; if 3 pts developed an SLT, the treatment would be deemed intolerable. Results: Sixteen women had rec uterine cancer and 4 had rec ovarian cancer. Recurrence sites included vaginal cuff (9), pelvic nodes (3) and supra-pelvic nodes (8). Median follow-up was 13.3 months (range 1.7-26.7).Median time from original diagnosis to relapse was 19 months. All 20 pts completed Bev and EB on schedule. One-year OS was 94% and RFS was 84%. To date, 3 of 20 pts have relapsed, all at distant sites. One pt had a high grade uterine carcinosarcoma and relapsed in the lung; 2 pts had ovarian cancer and relapsed in the lung and small bowel. No other relapses or persistent disease have been noted. Grade 4 lymphopenia was noted in 4 pts. No grade 4 toxicities and no gastrointestinal perforations were observed. Other grade 1 or 2 toxicities included fatigue, diarrhea or low white counts (total n=17). One ovarian cancer pt that relapsed developed a pulmonary embolus > 6 months after completing Bev. Conclusions: Delivering Bev for 3 doses with concurrent EB is safe, tolerable, and provides excellent local tumor control for women with recurrent gyn malignancies. Bev with EB should be considered for gyn malignancies in future trials.
Sarcopenia with modified Glasgow prognostic score as a predictor of long-term survival in patients with gastric cancer.
Authors: Masaaki Nishi, Mitsuo Shimada, Kozo Yoshikawa, Jun Higashijima, Toshihiro Nakao, Hideya Kashihara, Chie Takasu
Journal: Journal of Clinical Oncology (2016)

27 Background: Recent reports suggested that the Glasgow prognostic score (GPS), which is a preoperatively determined inflammation-based score, correlated with long -term survival in several types of cancers. The aim of this study is to create new prognostic index which is superior to modified GPS (mGPS) in gastric cancer. Methods: Seventy five patients with gastric cancer who underwent gastrectomy were enrolled in this study. Prognostic factors were searched for among clinocopathological factors and nutritional- or immune- parameters, including mGPS (J Gastoenterol 2011), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), or sarcopenia. Cut of value were 3.0: NLR, 40: PNI, respectively. Sarcopenia was assessed by the following CT-based methods (Lancet 2011). Sarcopenia with mGPS (SarcoGPS) were defined as CRP was changed to sarcopenia. Results: The overall survival (OS) rate was significantly lower in mGPS:0 group than in mGPS:1,2 group (p &lt; 0.05). The disease-free survival (DFS) rate didn’t differ in mGPS (N.S). The OS and DFS rate of high NLR group or sarcopenia group were significantly lower than those of low NLR group or non- sarcopenia group (p &lt; 0.05). PNI did not differ significantly both in OS and DFS. SarcoGPS was the poor prognostic factor both in OS and DFS (p &lt; 0.01) Conclusions: SarcoGPS is the new prognostic index, which is superior to mGPS, in gastric cancer.
Long-term efficacy and pharmacodynamic parameter analysis in pretreated KRAS-mutant metastatic colorectal carcinoma (mCRC) patients treated with RG7160 (GA201), an antibody-dependent cellular cytotoxicity (ADCC)-enhanced monoclonal anti-EGFR antibody.
Authors: Jean-Pierre Delord, Josep Tabernero, Rocio Garcia-Carbonero, Andres Cervantes-Ruiperez, Carlos Alberto Gomez-Roca, Yann Berge, Jaume Capdevila, Jesus Corral Jaime, Desamparados Roda Perez, Sophie Golding, David Oppenheim, Sophia Soehrman Brossard, Christoph Mancao, Farzin Farzaneh, Alexandre Passioukov, Luigi Manenti, Marion Gabriele Ott, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2013)

379 Background: EGFR-positive, KRAS-mutant mCRC patients (pts) do not benefit from anti-EGFR treatment. In this pt population we investigated the efficacy of single-agent GA201, a novel dual acting, anti-EGFR antibody which was glycoengineered to enhance ADCC on top of signaling blockage. This stimulation of immune effector cells may improve long term clinical outcomes. Methods: In an open-label, multicenter, non-randomized study, KRAS-mutant mCRC pts (1-2 prior chemotherapy lines) were treated with GA201 (1400 mg on day 1 and 8 then by 1400 mg q2W). The primary endpoint was to investigate tumor response. Here we report response rates, overall survival (OS) and pharmacodynamics analyses from archival, pre- and on-treatment biopsies and blood samples. Results: 25 pts received a median of 5 GA201 infusions (range 2–24), for up to 414 days. Median overall survival was 9.3 months (range 1.2 – 21.2). Best overall response was stable disease (40% of patients at 8 weeks), which was maintained in 24% of pts at 16 weeks, in 2 patients (8%) at 24 weeks and 1 pt (4%) at 42 weeks. Treatment-related adverse events were all manageable with rash (20% grade3), hypomagnesaemia (20% g3/4) and infusion-related reactions (4% g3) being the most common adverse events; none led to discontinuation or dose reduction. Comparison of pre- and post-treatment tumor biopsies evaluable for 11 pts revealed that tumor-infiltrating cell counts increased notably after one cycle of therapy (median composite immune reactive score of 1491 vs 898 cells/mm 3 at baseline). In addition, it was noted that EGFR H-score in baseline tumor biopsies was notably higher than in archival tumors (median [range] 52 [13–161] vs 3 [1–81], respectively). High tumor immune cell infiltration at baseline might be associated with better treatment outcome and long-term survival. Conclusions: Encouraging OS is achieved with GA201 monotherapy in patients with KRAS-mutant tumors. The pharmacodynamics analyses support the hypothesis of triggering an enhanced long term immune response in this pretreated patient population. Clinical trial information: NCT00721266.
The efficacy and safety outcomes of bevacizumab and systemic therapy in metastatic colorectal cancer patients with peritoneal disease in the AGITG MAX clinical trial and in nontrial patients in two cancer centers.
Authors: Aflah Roohullah, Katrin Marie Sjoquist, Val Gebski, Weng Ng, Wei Chua, Timothy Jay Price, Niall C. Tebbutt, Lorraine A. Chantrill
Journal: Journal of Clinical Oncology (2014)

595 Background: Metastatic colorectal cancer with peritoneal disease (PmCRC) represents a phenotype that may derive a greater clinical benefit from bevacizumab (BEV) due to the effect of VEGF on peritoneal spread and ascites production. However, there is concern of greater adverse events, in particular GI perforations. We investigated the clinical benefit and safety of adding BEV to chemotherapy in PmCRC in clinical trial and nontrial populations. Methods: We compared PFS and OS in PmCRC patients receiving first-line chemotherapy with and without BEV in: (1) the AGITG MAX trial (capecitabine [CAP] vs CAP/BEV +/- mitomycin C) and (2) two cancer centers in New South Wales between Jan 2005 and Dec 2012 (any regimen +/- BEV). Secondary endpoints included chemotherapy duration and GI adverse events. Time to event outcomes were estimated using the method of Kaplan-Meier and comparisons made using the logrank test. Proportional hazards models were used to obtain hazard ratios for regression analysis. Results: See Table. 84 MAX and 69 nontrial pts had PmCRC and there was a 37% reduction in the risk of progression in those receiving BEV, which is similar when compared to the nonperitoneal disease pts (HR= 0.63 95% CI 0.52-0.79 p value &lt; 0.001). OS in the PmCRC group was significantly worse than the nonperitoneal group (14.3 months vs 18.8 months p value = 0.02). Chemotherapy duration was similar across the groups. The rate of notable GI adverse events, including GI perforation was not increased in the PmCRC group receiving BEV in either cohort. One pt had a GI perforation after receiving CAP+BEV. Conclusions: Pts with mCRC and peritoneal disease receiving first-line therapy in trial and nontrial populations appear to derive a similar proportional benefit when BEV is added to systemic therapy without an increase in GI adverse events. However, this subgroup of patients continues to have a worse prognosis. [Table: see text]
Review of cost-effectiveness studies on aromatase inhibitors for the treatment of early-stage breast cancer.
Authors: O. Topaloglu, A. Unalp
Journal: Journal of Clinical Oncology (2010)

e11030 Background: With the recent updates of clinical guidelines of the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), aromatase inhibitors have been included in the management of early-stage breast cancer. There has been a great interest to understand the cost-effectiveness of this new alternative therapy which is becoming an optimal therapy for breast cancer. The objective of this study is to review the cost-utility studies on aromatase inhibitors for the treatment of early-stage breast cancer and compare reported incremental cost- effectiveness ratios (ICERs). Methods: We conducted a literature for cost-utility studies on anastrazole, letrozole and exemestane. We reviewed the papers to extract the information on intervention, comparator, ICER, country, perspective, time horizon and clinical data used. For the comparison of reported ICERs, we converted all currencies to U.S. dollars by exchange rate for the cost-year used, then inflated the values to 2008. Results: A total of 20 papers were identified (8 on anastrazole, 8 on letrozole and 4 on exemestane). All studies were from health care perspective and sponsored by manufacturers. The time horizon modeled ranged from 7.5 years to lifetime, however majority of the studies modeled lifetime. The studies were from EU countries and North America such as U.S., Canada, Belgium, Italy, Sweden and U.K. The mean ICER values were $24,932 for anastrazole, $21,113 for letrozole and $21,428 for exemestane. Conclusions: The mean ICERs for all three aromatase inhibitors are below $25,000; hence they appear to be cost-effective compared to tamoxifen therapy for the treatment of early-stage breast cancer. No significant financial relationships to disclose.