tbuckley/cabot-search huggingface dataset:
Outcomes with Radium-223 therapy in clinical practice of metastatic castration resistant prostate cancer (mCRPC).
Authors: Ajjai Shivaram Alva, Luke T. Nordquist, Stephanie Daignault, Saby George, Jorge Ramos, Sudhir Isharwal, Matthew McDonald, Gregory Campbell, Pongwut Danchaivijitr, Costantine Albany, Evan Y. Yu
Journal: Journal of Clinical Oncology (2015)

e16073 Background: Radium-223 use in clinical practice is challenged by paucity of data on biomarkers and optimal sequencing of radium-223 with other therapies. We sought to identify potential variables associated with outcomes after radium-223. Methods: Consecutive non-trial mCRPC patients (pts) who received ≥ 1 dose of radium dichloride-223 at 4 academic and 1 community urology specific cancer centers from May 2013-June 2014 were included. Association of clinical variables (including demographics, ECOG PS, prior therapy, pain scores, PSA, alkaline phosphatase) with number of doses of radium and outcomes (including PSA, alkaline phosphatase, survival) were analyzed using chi-square statistics, cox proportional hazards, and Kaplan Meier methods. Results: In the 145 eligible pts ( 89% Caucasian, mean age 71.4 years, BMI 29.4 kg/m2,ECOG PS 0-1 in 79%),prior therapy included abiraterone (66%), enzalutamide (49%), chemotherapy (60%) and bisphosphonate/denosumab (39%). At baseline, 67% were on opiates and median pain on the visual analog scale was 2 (IQR: 0-4). Radium-223 was administered for 6 cycles in 51%. In patients with baseline pain (n = 72), pain declined in 51% and increased in 7% after 1 dose; overall, pain declined in 81% with radium. In pts with no baseline pain (n = 43), 9 (21%) reported pain after 1 dose and of these, 5 reported decline with subsequent doses. PSA declined ≥ 50% in 16% (18/110). Alkaline phosphatase declined ≥ 25% in 48% (33/69). One-year survival was 64% (95%CI: 54-73%). Grade ≥ 3 neutropenia, anemia and thrombocytopenia occurred in 4% (n = 114), 4% (n = 125) and 5% (n = 123) respectively & did not vary by prior chemotherapy. Ability to receive all 6 doses was associated with ECOG PS 0-1, low baseline PSA & pain, no prior abiraterone/enzalutamide, and normal alkaline phosphatase. In univariate & multivariate analysis, survival was highly associated with receiving 6 doses of Radium-223. Conclusions: Radium-223 therapy is well tolerated with pain score declines. Pts receiving 6 doses show the best survival. Pts with good ECOG PS earlier in the disease course may be optimal candidates. Association with imaging assessed tumor burden in bone will be presented.
The use of routine surveillance imaging scans in women with early breast cancer (EBC) treated in Ontario, Canada.
Authors: Katherine Enright, Mohammed Ghannam, Lingsong Yun, Nathan Taback, Christopher M. Booth, Maureen E. Trudeau, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

6628 Background: Over use of routine surveillance imaging to detect recurrence in women with EBC was recently identified as one of the top five opportunities to improve the quality of cancer care by the American Society of Clinical Oncology. We undertook a population level assessment of the current practice of surveillance imaging in EBC women treated in Ontario Canada. Methods: Incident early breast cancer patients diagnosed 01/07 – 12/09 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. Basic (chest x-ray, abdominal x-ray and abdominal ultrasound) and advanced (computed tomography [CT] or bone scans) surveillance imaging scans completed during the first and second year of follow-up care (starting 6 months after surgery or upon completion of adjuvant chemotherapy) were identified. Logistic regression models were used to identify covariates associated with advanced surveillance imaging. Results: 16,981 EBC patients were included in the analysis of which 7,907(46.6%) received chemotherapy. In the first year of follow up care, 8,311 (48.9%) had at least 1 basic imaging test, while 4,916 (29.0%) had advanced imaging. This fell to 45.7% (basic) and 25.1% (advanced) in the second year of follow-up. Bone scans were the most common advanced imaging test (14.5%), followed by CT thorax (10.8%). On multivariable analysis age, stage, the use of chemotherapy and comorbidity were associated with increased use of advanced surveillance imaging (Table). Significant geographic variation was also demonstrated. Conclusions: Surveillance imaging was common in the first two years of follow-up for EBC patients. While appropriate for symptom driven investigation, attention should be paid to the routine use of surveillance imaging in EBC women during follow-up care. [Table: see text]
Pharmacodynamic effect of ipilimumab on absolute lymphocyte count (ALC) and association with overall survival in patients with advanced melanoma.
Authors: Michael Andrew Postow, Scott D. Chasalow, Jianda Yuan, Deborah Kuk, Katherine S. Panageas, Michael Cheng, Vafa Shahabi, David Mark Berman, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2013)

9052 Background: Ipilimumab (Ipi) is a fully human monoclonal antibody that augments antitumor T-cell responses. Ipi has been shown to improve overall survival (OS) in 2 phase (ph) III trials of advanced melanoma, as monotherapy at 3 mg/kg in previously treated patients (pts) (MDX010-20) or at 10 mg/kg with dacarbazine in previously untreated pts (CA184-024). In preclinical and clinical studies, inhibition of CTLA-4 by Ipi resulted in increases in activation and proliferation of peripheral T cells and increases in ALC. Baseline ALC may be a prognostic biomarker in several cancer types. The current analyses aim to increase understanding of changes in ALC with Ipi treatment and association of these changes with OS. Methods: Data were from 6 studies of Ipi with chemotherapy (CT) (ph I 078; N=59) or without CT (ph III MDX010-20; ph II trials 004, 007, 008, and 022; N=1203), and Ipi monotherapy in an Expanded Access Program (N=117) or with commercially available Ipi (N=71) or BRAF inhibitors (N=39). ALC was measured at baseline, prior to each dose during induction (weeks 1, 4, 7, and 10) and at the end of induction (week 13). Cox proportional hazards models were used to estimate and test associations between ALC measures and OS. Results: In all studies, mean ALC increased significantly over time in pts who received Ipi, with or without CT (P&lt;.0001 to P=.03). There was no significant mean increase in ALC in pts who received gp100 or BRAF-inhibitor monotherapy. In study MDX010-20, pts with a greater rate of change in ALC from baseline to week 7 tended to have longer OS (P=.0003). A similar association was found between OS and ALC ≥1000/µL after 2 Ipi doses. However, pts in MDX010-20 had an OS benefit from Ipi relative to gp100, regardless of rate of change in ALC (P=.14). Conclusions: In these analyses, consistent with inhibition of CTLA-4, Ipi induced an increase in mean ALC, even with the addition of CT. A positive association between rate of ALC increase and OS was observed, but this was not specifically predictive of OS benefit from Ipi. Therefore, ALC cannot currently be used to guide clinical management with Ipi. However, further prospective investigation may be warranted.
Health behaviors among testicular cancer survivors.
Authors: Steven C Palmer, Linda A. Jacobs, James C. Coyne, David J. Vaughn
Journal: Journal of Clinical Oncology (2012)

9145 Background: Testicular cancer survivors (TCS) experience elevated risk for cardiovascular issues including coronary artery disease that present a greater threat to their long-term health than recurrence of cancer. These risks may be moderated by health behaviors (HBs), yet little is known about HBs or their barriers in this population. This is unfortunate, as these barriers may serve as intervention targets. This study examined HBs and their barriers in a population-based sample of TCS. Methods: TCS were recruited through the PA Cancer Registry. Eligible individuals were diagnosed with testicular cancer between 1990 - 2007 and provided informed consent. Participants completed measures of tobacco use, alcohol use, dietary habits, physical activity, BMI, quality of life (QOL), and barriers to performing HBs, as well as self-reported disease and treatment information. Results: 189 participants provided data. Participants were middle-aged (M=44 yrs. R=19-59), predominately white (95%), married (72%), parents (69%), 6.8 years post-diagnosis (R=1-19), and at normative levels for physical and psychosocial QOL. A substantial minority (31%) was unaware of their disease stage or histopathological type (27%), although 89% reported surgery, 32% chemotherapy, and 53% XRT. Almost 25% reported current tobacco use, and 35% reported “risky” alcohol use. Adequate aerobic activity was reported by half, but only 28% reported adequate strength and flexibility activities. 84% reported above normal BMI, with 35% in the obese range. Barriers to HBs included cancer-related problems (e.g., neuropathy, pain, hernia risk) and competing demands (e.g., work responsibility, time constraints). Cancer-related barriers were related to worse physical QOL and higher BMI. Competing demands predicted worse psychosocial QOL, unhealthy eating, and inadequate physical activities. Conclusions: Given the negative HBs in this sample and their potential cardiovascular risk, interventions aimed at reducing tobacco and risky alcohol use, as well as improving dietary and physical activity levels are needed. These interventions will likely need to overcome perceived barriers to adoption of HBs in order to be successful.
Comprehensive analyses of rectal cancer genomes to reveal copy number variations as potential predictor of induction therapy efficacy.
Authors: Julia Beck, Jochen Gaedcke, Howard B. Urnovitz, Kirsten Bornemann-Kolatzki, Marian Grade, William Marvin Mitchell, Michael Ghadimi, Ekkehard Schütz
Journal: Journal of Clinical Oncology (2014)

e14549 Background: Genetic aberrations such as SNPs and structural aberrations are associated with malignancies and cancer is regarded as a disease of the genome. Genome profiling of individual tumors is provided by high-throughput sequencing and is about to enter routine clinical practice with impact on treatment decisions and tumor classification (NIH [2014] The Cancer Genome Atlas). Rectal tumors show a great variation in response to preoperative chemoradiotherapy and, therefore, robust and easy to obtain individual biomarkers are needed in order to adjust treatment strategies for each patient. Methods: Copy-number profiles were generated for 13 rectal tumors (pre CRT; Stage II or higher) using shotgun sequencing (HiSeq). For a subset of the tumors (n=10) the 20 genes most commonly mutated in colon cancer were screened for mutations using the commercially available GeneRead DNAseq Colon Cancer Gene Panel (QIAGEN) with subsequent sequencing using an Illumina MySeq. Results: The copy-number profiles of the 13 tumors revealed frequent gains of chromosomes 8q(54%), 13q(69%) and 20q(62%) and frequent losses of 1p(62%), 8p(77%), 14q(54%), 17p(62%) and 18(77%). Exon sequencing of only 20 genes most commonly mutated in colon cancer revealed at least one SNP with high or moderate clinical impact for each tumor (median=3.5 (range: 1-7)). Six of the ten tumors carried mutations in TP53 and APC, respectively, and five tumors have KRASmutations. The number of somatic amplifications in the individual tumor genome correlated significantly with the regression in tumor mass by CRT (r=0.7, p=0.008). Conclusions: The detected copy-number aberrations of these rectal carcinomas are in agreement with former studies of colorectal tumors (Xie T, G DA, Lamb JR, et al. 2012. A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations. PLoS One 7: e42001.) and all of the analyzed tumors carry several regions of abnormal copy-number state. The detected number of amplification may serve as predictor for a successful preoperative CRT.
Evaluation of the feasibility of expression microarray analysis in endoscopically obtained biopsies of gastric carcinoma and their clinical applicability
Authors: M. P. Jhawer, L. Qin, H. Gerdes, D. Klimstra, M. Schattner, A. Viale, M. Gonen, G. Schwartz, D. Kelsen, M. Shah
Journal: Journal of Clinical Oncology (2007)

21164 Background: The feasibility of extracting high quality RNA for expression microarray analysis from endoscopic biopsy in gastric carcinoma has not been previously established. Methods: Patients with histologically confirmed locally advanced gastric or gastroesophageal junction adenocarcinoma were screened for enrollment in an NCI-sponsored trial of neoadjuvant irinotecan and cisplatin chemotherapy (NC1–5917). All patients underwent a repeat endoscopic biopsy for the procurement of fresh tumor tissue. Gross microdissection was performed to enrich the sample to at least 80% malignancy. RNA was isolated from the tumor specimens using RNeasy columns (Qiagen) and its quality verified by RNA 6000 NanoAssay and Bioanalyzer 2100 (Agilent). Gene expression profiling was performed on Human Genome U133A GeneChip (Affymetrix) which contained 22,215 oligonucleotide-base probe-sets. Differential gene expression profiles for Lauren's classification were assessed using empirical Bayes t test, a threshold p &lt; 0.001 was considered statistically significant. Results: Of 36 patients with previous biopsy confirmed gastric cancer, repeat endoscopic biopsy identified carcinoma in 28 patients (78%, 95%CI 61–90%). Adequate RNA for microarray analysis was obtained from 21 patients-representing 58% of those who presented for the procedure and 75% in whom endoscopic biopsies confirmed malignancy. This yield improved with increasing number of samples taken. Lauren's classification was available on 26 patients who underwent resection. From the total 54,613 gene probe-sets on the arrays, comparison of the expression profiles of diffuse-type and intestinal-type identified 167 genes that were differentially expressed. Diffuse gastric cancer demonstrated altered expression of genes related to cell-matrix interaction whereas intestinal gastric cancer expression analysis showed enhancement of cell growth. Conclusions: Endoscopic biopsy for expression analysis of gastric cancer is feasible with increasing yield with each core taken. Expression analysis at the time of endoscopic biopsy can differentiate Lauren's histology, a characteristic not routinely evaluable by pathologic review. No significant financial relationships to disclose.
Performance in a Scottish cancer network (SCAN) against ASCO/NCCN clinical quality measures for breast and colorectal cancers
Authors: C. Dodds, U. Chetty, G. Wilson, P. Muir, A. Gregor
Journal: Journal of Clinical Oncology (2007)

17001 Performance in a Scottish cancer network (SCAN) against ASCO/NCCN Clinical Quality Measures for breast and colorectal cancer. Background: South East Scotland Cancer Network (SCAN) aims to improve care, treatment, and equity for all cancer patients in the 1.4m population under its care ( www.scan.scot.nhs.uk ). Clinical care is delivered by multidisciplinary teams in 7 hospitals and one regional cancer centre. Key function of the network is prospective audit collecting externally validated information on evidence-based performance indicators. Method: Cohorts of 624 breast and 359 colorectal cancer patients diagnosed over a 12-month period in Lothian have been analysed against the ASCO/NCCN measures. Conclusions: SE Scotland Breast and Colorectal services compare favourably with the ASCO/NCCN standards of care on most measures. Use of radiotherapy in rectal cancer conforms to Scottish guidelines. [Table: see text] No significant financial relationships to disclose.
Prescribing preferences of U.S. oncologists for patients (Pts) with metastatic urothelial carcinoma (mUC) at first recurrence: Impact of novel agents.
Authors: Maria L. Lankford, Joanne P. Willey, Arden Buettner, Susan Lynne Britton, Mitch Scharf, Robert Dreicer
Journal: Journal of Clinical Oncology (2017)

365 Background: In May 2016 atezolizumab (A) was approved for the treatment of pts with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy (PCCT), or within 12 months (mos) of neoadjuvant or adjuvant treatment with PCCT. We evaluated prescribing preferences (PPrefs) of 248 U.S-based oncologists for 1 st recurrence treatment across a range of clinical scenarios prior to and following A approval. Methods: PPrefs were assessed through a validated, case-based market research tool (Challenging Cases). Assessment dates were 3/5 and 4/30 (PRE-) and 8/6 (POST-approval). Data were acquired using blinded, audience-response technology. A core scenario (CS) and 5 variant scenarios (V1, 2, 3, 4, 5) were utilized. CS: 69-year-old pt with muscle invasive bladder cancer, with a CrCl 62 ml/min, Hgb 12.5, and PS 1, recurs in the liver and bone 18 months after receiving neoadjuvant gemcitabine/cisplatin and a radical cystectomy. V1: Same as CS but with reduced CrCl 48 ml/min. V2: Same as CS but recurrence at 6 months. V3: Same as V2 but multiple comorbidities and PS 2. V4: Same as CS but age 79. V5: Same as V4 but multiple comorbidities. The same query was posed in each setting: What therapy would you choose? Results: See Table. Conclusions: Following the approval of A, overall PPref of most regimens offered decreased across nearly all 1 st recurrence scenarios in favor of A. This is particularly stark in platinum unfit (older, comorbid, poor PS) pts. This highlights the previously unmet medical need in the PCCT pre-treated mUC pts. [Table: see text]
Bone metastases in patients with relapsed/refractory germ cell tumors (GCT) undergoing first salvage chemotherapy: A retrospective analysis of a large international database.
Authors: Karin Oechsle, Christoph Oing, Friedemann Honecker, Lars Arne Berger, Carsten Bokemeyer, Joerg Beyer, Anja Lorch
Journal: Journal of Clinical Oncology (2012)

4597 Background: Bone metastases (mets) are rare events in GCT patients (pts) and data on characteristics, risk factors, treatment and outcome in these pts are largely missing. Methods: A subgroup of 104 ptswith bone metsfrom the IPFSG database was analyzed. All patients experienced unequivocal relapse/progression after &gt; 3 cycles of cisplatin-based chemotherapy and received conventional-dose (CDCT) or high-dose salvage chemotherapy (HDCT). Results: 104 / 1594 pts presented with bone mets (6,5%) at first relapse. Histology was pure seminoma in 26%, and non-seminoma in 74%. At initial diagnosis, 54% of pts had presented with "poor risk" according to IGCCCG. Overall response rate (ORR; CR+PR) to 1 st -line chemotherapy was 89%. Median PFS after primary treatment was 3 months (range 0 - 140). Bone mets at first relapse were accompanied by abdominal, lung, mediastinal, liver and brain mets in 54%, 48%, 28%, 36%, and 14%, respectively. Tumor marker profiles were heterogeneous (elevation of AFP / ß-HCG: 51% / 37%). Salvage treatment was CDCT in 34%, and HDCT in 66% of pts. ORR to salvage chemotherapy was 68% for the total cohort, and 43% vs. 81% for CDCT vs. HDCT (p&lt;.01). For the total cohort, 2y-PFS and 5y-OS were 24% and 16%, respectively. 2y-PFS and 5y-OS were significantly higher in pts after HDCT compared to CDCT (2y-PFS 29% vs. 14%, p=.01; 5y-OS 19% vs. 9%, p=.04). Conclusions: Pts relapsing with bone mets after platinum-based CTX were characterized by "poor risk" disease at initial diagnosis, but characteristics at first relapse were heterogeneous. Treatment response and outcome was improved in pts with HDCT compared to CDCT. Further prospective evaluation of characteristics and treatment approaches in GCT pts with bone mets is warranted.
Long-term psychological reactions among lymphoma survivors.
Authors: Donna M. Posluszny, Mary Amanda Dew, Ellen Ingalls Beckjord, Dana H. Bovbjerg, John E. Schmidt, Carissa A. Low, Amy Lowery, Stephanie Nutt, Sarah R. Arvey, Ruth Rechis
Journal: Journal of Clinical Oncology (2014)

e20585 Background: Adult-onset lymphoma can carry a generally favorable prognosis, reflected in the growing population of lymphoma survivors. Little is known about lymphoma survivors’ existential concerns (perceptions of a lost sense of security in the future, lost sense of identity, grief and guilt about seeing other cancer patients die, and worries about their own cancer). We examined these concerns with data from the 2010 LIVESTRONGSurvey. Methods: Lymphoma survivors (n=429; mean age=45, mean=7.0 years post-diagnosis) responded to an online survey between 6/2010 and 3/2011 that asked whether they had experienced the following due to their cancer experience: a lost sense of security in their future and a lost sense of identity, grief and guilt over other cancer patients’ deaths, and worry about their cancer prognosis and outcomes. Patient characteristics assessed included gender, age and medical characteristics (Hodgkin v. non-Hodgkin lymphoma, time since diagnosis, and type of treatment received: a stem cell transplant (SCT), and radiation or chemotherapy as a solo treatment or combined). Multivariate logistic and linear regressions were used to identify characteristics most likely to be associated with psychological sequelae. Results: Over one half (52%) of survivors felt a lost sense of security in their future, and 26% felt they had lost a sense of their identity due to their cancer experience. Regression analyses showed that patients with these concerns were more likely to have undergone SCT. A majority of the sample (70%) felt grief and 38% felt guilt over the death of other cancer patients. Both grief and guilt were more commonly endorsed by women, and individuals with a more recent diagnosis were more likely to report guilt. The majority (84%) endorsed at least some cancer worry, and 32% of this group reported that their activities had been limited by this cancer concern in the past week. Higher levels of cancer worry were reported by younger patients and by those who were diagnosed more recently. Conclusions: Many lymphoma survivors continue to experience psychological sequelae of cancer diagnosis, even years post treatment completion. Cancer worry is a main concern for survivors, and those who undergo SCT may be most at risk for existential concerns.