tbuckley/cabot-search huggingface dataset:
Impact of the 92-gene assay on cost of diagnosis of tumor type in metastatic cancer of uncertain origin.
Authors: Tanya G. Bentley, Brock Schroeder, Catherine A. Schnabel, Jesse Ortendahl, Wendy C. Hsiao, Mark G. Erlander, Michael S. Broder
Journal: Journal of Clinical Oncology (2013)

e15104 Background: Molecular classification of tumors has been incorporated into clinical algorithms for patients with metastatic cancers of uncertain origin. This study is a comprehensive cost analysis—characterizing standard of care for metastatic disease, cost implications of correct vs incorrect diagnosis, and cost effectiveness of implementing molecular classification into the diagnostic paradigm. Methods: A deterministic model was developed to project the cost and effectiveness of standard care for metastatic tumors of uncertain origin, compared with incorporating use of the 92-gene assay at 3 points: before immunohistochemical (IHC) analysis, or after 1, or 2 sets of IHC stains. For each strategy, total and incremental costs, life-years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratios (ICERs) were projected, as well as the % of patients treated correctly vs incorrectly. Model inputs and costs were based on published literature, analyses of the SEER database, the Physicians’ Fee and Coding Guide 2012, and interviews with disease experts. Sensitivity analyses were performed on key inputs. Results: When standard care was compared with each 92-gene assay strategy, costs increased between $4,804 and $6,038 and QA-survival by 1.03-1.15 months. Using the 92-gene assay after 1 set of IHC stains was the most cost effective strategy ($50,273/QALY). Overall, the 92-gene assay increased the % of patients treated correctly and decreased the % of patients treated with empiric therapy compared with standard care. When compared with incorrect treatment, correct treatment provided an additional 5.4 QA-months of survival. Sensitivity analyses identified that costs of empiric treatment, the 92-gene assay, and lung cancer treatment had the greatest effect on outcomes. At a societal willingness-to-pay (WTP) threshold of $100,000, the 92-gene assay was cost effective 94% to 99% of the time. Conclusions: Use of the 92-gene assay is considered cost effective using current societal WTP thresholds, represents an efficient use of economic resources that improves patients' survival and quality of life, and could contribute to standardization of the costs of diagnosis.
Interim analysis of a phase II randomized clinical trial of samrium-153 (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer after docetaxel.
Authors: Christopher Ryan Heery, Ravi A. Madan, Marijo Bilusic, Joseph W. Kim, Nishith K. Singh, Myrna Rauckhorst, Clara Chen, William L. Dahut, Walter Michael Stadler, Robert S. DiPaola, Mark N. Stein, James W. Hodge, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2012)

2526 Background: A prior randomized, placebo-controlled, multi-center phase 2 trial of PSA-TRICOM (PROSTVAC) demonstrated an overall survival benefit. Sm-153 is a radiopharmaceutical that targets osteoblastic bone lesions. Preclinical data indicated that Sm-153 could alter tumor phenotype, causing upregulation of Fas, MHC Class I, and tumor-associated antigens, making tumor cells more amenable to immune-mediated killing. Methods: This is a phase 2 multi-center trial design intended to randomize 68 patients (pts) to Sm-153 with or without PROSTVAC. Eligibility included castrate resistant prostate cancer bone metastases, no visceral disease, prior docetaxel, ECOG ≤2, and normal organ function. Sm-153 was given at 1mCi/kg IV on day 8 and then every 12 weeks. PROSTVAC was given on days 1, 15, 29, then every 4 weeks. The 1° endpoint is a comparison of progression-free survival at 4 months (mo) utilizing PCCWG, but not PSA criteria. 68 patients will provide 80% power to detect a difference of 15% vs. 40% without progression at 4 mo with a one-tailed alpha = 0.10 assuming Fisher’s exact test comparing these fractions as the primary method of analysis. 2° endpoints are OS, ORR, PSA changes, immunologic, toxicity, and palliation. Reported here is the result of a pre-specified interim analysis, which required ≥20% conditional power to detect 15% vs. 40% without progression at 4 months for the trial to continue. Results: Of 37 enrolled pts, 3 were not evaluable for PFS. PFS and PSA findings are found below. Hematologic toxicities (anemia, thrombocytopenia, neutropenia, or lymphocytopenia) are most common, with grade 3 or 4 thrombocytopenia occurring in 22% and 26% of treatment cycles on Arms A and B, respectively. The conditional power for the comparison of fractions without progression at 4 mo is 77%. Conclusions: This interim analysis suggests the combination of PROSTVAC and Sm-153 is well tolerated with similar toxicity profile to Sm-153 alone. The early indication of improved TTP warrants continued study accrual. [Table: see text]
A pilot trial of topotecan administered orally in patients with advanced solid tumors expressing hypoxia inducible factor (HIF)- 1α
Authors: G. Melillo, M. Gutierrez, B. Holkova, A. Rapisarda, M. Raffeld, Y. Horneffer, R. Chang, A. J. Murgo, J. H. Doroshow, S. Kummar
Journal: Journal of Clinical Oncology (2007)

14103 Background: HIF-1 is a transcription factor frequently over-expressed in common human cancers that mediates a transcriptional program leading to tumor angiogenesis, survival and metastases. Previous studies have demonstrated that daily administration of topotecan (TPT), a topoisomerase I poison, inhibits HIF-1a expression, angiogenesis and tumor growth in human xenograft models. The primary aim of this study is to investigate whether TPT inhibits HIF-1a expression in human cancers. Methods: TPT was administered orally at 1.6 mg/m 2 daily x 5 for 2 weeks, on a 28-day cycle, to adult patients with advanced solid tumors expressing HIF-1a in at least 10% of tumor cells, as assessed by IHC. Tumor biopsies are obtained before and at the end of treatment in cycle 2 and tested for HIF-1a protein expression by IHC and mRNA expression of HIF-1 target genes by real-time PCR. 18 FDG-PET, to assess tumor metabolism, and DCE-MRI, to assess blood flow and permeability, were obtained at baseline, at the end of 2 weeks of therapy and then at the end of treatment on cycle 2. CT scans were performed before and after 2 cycles of therapy. Serial blood samples are obtained for PK analysis. Results: Seven patients, median age 54 (range 35–70), have been treated so far, with 6 patients being evaluable for the primary endpoint with paired tumor biopsies for analyses: melanoma (1), colorectal cancer (2), bladder (1), breast (1), ovarian (1). First two patients received the planned dose of 1.6 mg/m 2 ; patient # 2 developed grade 3 neutropenia and grade 4 thrombocytopenia. As the objective was to develop a regimen for chronic dosing that was well tolerated and not directly cytotoxic, the protocol was amended to reduce the dose. Four patients have received a median of 2 cycles at 1.2 mg/m 2 , which has been well tolerated. A decrease of VEGF mRNA expression by more than 70% was observed in the 2 patients treated at 1.6 mg/m 2 after 2 cycles of treatment. However, no consistent decrease of HIF-1a protein levels was detected in the corresponding tumor tissue. Enrollment continues. Conclusion: This is the first study aimed to validate inhibition of the HIF-1 signaling pathway in cancer patients. Funded in part by NCI Contract N01- CO-12400. No significant financial relationships to disclose.
The effect of FGFR4 Gly388Arg polymorphism on treatment outcomes after chemoradiotherapy in esophageal cancer patients.
Authors: Sanghee Cho, Hyung-jung Shim, Jun-Eul Hwang, Woo Kyun Bae, Taek-Keun Nam, Min-Ho Shin, Sook-In Jung, In-Jae Oh, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2014)

4040 Background: Fibroblast growth factor receptor 4 (FGFR4) has been associated with increased risk, staging, and metastasis in several type of cancer. The purpose of this study was to evaluate the prognostic role of FGFR4 Gly388Arg polymorphism in esophageal cancer after chemoradiotherapy. Methods: Peripheral blood samples from 250 patients who were treated with chemoradiotherapy were used for this study. Patients were diagnosed as a stage of I in 12 (5%), II in 54 (21%), III in 115 (46%) and IV in 69 (28) patients. All of the patients were received chemotherapy using cisplatin and fluorouracil or cisplatin and docetaxel. Results: The overall response was 85%, with 21% complete response and 64% partial response. The overall survival (stage II, 34 months; stage III, 23.3 months; stage IV, 19.3 months, p=0.005) and progression survival (stage II, 23.8 months; stage III, 12.8 months; stage IV, 9 months, p=0.001) was significantly improved according to stage. In FGFR4 genotypic analysis, 96 patients (38.6%) were homozygous for Gly388 allele, with 113 heterozygous (45.4%) and 40 (16.0) homozygous for Arg388 allele. There was no significant association between FGFR4 genotype and stage. However, Gly388 allele patients show better overall response rate (90.6%) than Arg388 carriers (82.4%, p=0.050). In early stage (stage I and II, n=66), Gly388 allele patients tended to have a better OS or PFS (not available until this analysis) than Arg388 carriers (PFS: 38 months, 95% CI 7.7-68.1; OS: 49 months, 95% CI 24.8-73.5). However, in advanced stage (III, IV), the survival outcomes was similar between genotypes. Conclusions: Present study shows that FGFR4 Gly388 allele has a prognostic role in response after chemoradiotherapy in esophageal cancer. Especially in early stage of esophageal cancer, FGFR4 might have an important role in disease progression and survival outcomes. It suggests that the possibility of new therapeutic target for esophageal cancer treatment.
Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma
Authors: Fauzia Shaikh, Marjorie G. Zauderer, Donata von Reibnitz, Abraham J. Wu, Ellen D. Yorke, Amanda Foster, Weiji Shi, Zhigang Zhang, Prasad S. Adusumilli, Kenneth E. Rosenzweig, Lee M. Krug, Valerie W. Rusch, Andreas Rimner
Journal: Journal of Thoracic Oncology (2017)
Five-year trajectories of financial recovery in low-income breast cancer survivors.
Authors: Victoria Susana Blinder, Sujata Patil, Francesca Gany, Rose C. Maly
Journal: Journal of Clinical Oncology (2013)

9597 Background: Breast cancer may have devastating consequences on the financial stability of low-income families due to its impact on employment and limited duration of emergency Medicaid coverage. Methods: A consecutive sample of 921 low-income, uninsured/underinsured, English/Spanish-speaking women diagnosed with breast cancer through the California Breast and Cervical Cancer Treatment Program was surveyed 6 months after diagnosis. Previously uninsured women were enrolled in MediCal. Follow-up surveys were administered at 18, 36, and 60 months. Our primary outcome was self-reported adequacy of financial resources. Trajectories of financial adequacy were compared by ethnicity and by trajectories of employment and insurance status. Results: 6 months after diagnosis, 38% said they had adequate financial resources to meet their needs, compared to 39%, 49%, and 55% at 18, 36, and 60 months, respectively. Trajectories of financial adequacy varied by ethnicity and by trajectories of employment and insurance status (Table). Of 549 who reported on financial resources in all 4 surveys the most common trajectory was inadequate resources in all surveys (n=120) followed by adequate resources in all surveys (n=83). Of 208 who had adequate resources at 6 months, 60% reported inadequate resources in ≥1 subsequent survey. Of 341 who had inadequate resources at 6 months, 87% reported inadequate resources in ≥1 subsequent survey. Conclusions: Low-income breast cancer survivors are at risk of long-term financial instability. Latinas and survivors who are not working and/or are uninsured are at highest risk. Additional research is needed to better understand the factors that impact financial recovery after treatment. [Table: see text]
ADHERENCE to regorafenib therapy in patients with metastatic colorectal cancerpreviously treated metastatic colorectal cancer: STI observational multicenter study.
Authors: Salvatore Del Prete, Raffaele Addeo, Vincenzo Montesarchio, Luigi Leo, Antonio Febbraro, Guido Giordano, Clementina Savastano, Roberto Mabilia, Gregorio Cennamo
Journal: Journal of Clinical Oncology (2015)

e17529 Background: Oral agents for anticancer therapy provide an attractive approach for patient acceptance and use of oral treatments is increasing. Adherence can be defined as the extent to which a patient’s behavior coincides with medical advice. Patient Adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure acceptance and adherence among patients with metastatic colorectal cancer previously treated with chemotherapy and other target therapy agents. Methods: Overall 64 patients with histologically proven metastatic colorectal cancer treated with oral regorafenib 160 mg once dailywere enrolled. The level of acceptance was evaluated using a questionnaire with ten questions administered every 2 months thereafter during the treatment. Patients scored each item on a 5-point ordinal scale range ranging from 0 to 4 during the previous 7 days. The adherence to the treatment was measured using the patient-completed medication diaries, the physician interview and pill count requiring patients to return unused pills at each visit. These evaluations were achieved every month during the treatment Results: Sixty-four patients treated with Regorafenib were enrolled between January 2014 and november 2014 and were included in the study analysis. The median age was 62 years and the median performance status was 1. We found a statistically significant improvement of therapy sharing measured by the acceptance questionnaire Average adherence was 86% across six months of treatment for all patients with complete data for any month. Interestingly, we found that the occupation is not crucial for the adherence, instead of the marital status, married patients were more adherent to the treatment probably related to the fundamental support offered by the family. The level of acceptance of therapy was significantly related to the adherence. Conclusions: Despite the advanced disease, most patients accept the therapy without any difficulties. Final results will be presented at 2015 ASCO Meeting.
Unproven Technologies in Maternal-Fetal Medicine and the High Cost of US Health Care
Authors: Steven L. Bloom, Kenneth J. Leveno
Journal: JAMA (2017)

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Prospects for combining targeted and conventional cancer therapy with immunotherapy
Authors: Philip Gotwals, Scott Cameron, Daniela Cipolletta, Viviana Cremasco, Adam Crystal, Becker Hewes, Britta Mueller, Sonia Quaratino, Catherine Sabatos-Peyton, Lilli Petruzzelli, Jeffrey A. Engelman, Glenn Dranoff
Journal: Nature reviews. Cancer (2017)
Cetuximab biweekly plus mFOLFOX6 as first-line therapy in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC): An interim analysis of the CEBIFOX trial.
Authors: Stefan Kasper, Johannes Meiler, Heike Knipp, Thomas Hoehler, Peter Reimer, Tilman Steinmetz, Winfried Berger, Gabriele Linden, Saskia Ting, Peter Markus, Andreas Paul, Martin H. Schuler, Tanja Trarbach
Journal: Journal of Clinical Oncology (2013)

e14502 Background: Combination of mFOLFOX6 with weekly cetuximab is a standard first line regimen in pts with KRAS wt mCRC. Weekly application of cetuximab increases the in-hospital time of pts with negative impact on quality of life. This multicentric phase II trial evaluates the efficacy of mFOLFOX6 + biweekly cetuximab as first line therapy in KRAS wt mCRC. Methods: Pts with KRAS wt mCRC who were not candidates for primary metastasectomy received cetuximab (500 mg/m 2 every 2 weeks) in combination with mFOLFOX6 (oxaliplatin 85 mg/m 2 , folinic acid 400 mg/m 2 , 5-FU 400 mg/m 2 bolus and 2,400mg/m 2 over 46 h q14d). Primary endpoint was objective response rate (ORR) per RECIST 1.0, secondary endpoints were safety, secondary resection rate, quality of life (QoL), progression-free survival (PFS) and overall survival. Data of a pre-specified interim analysis are presented in which 13 responders were needed in the first 37 pts (Simon stage I). Results: As of Dec 2012, 46 pts were registered. Fourty three pts received ≥1 course of treatment, and 34 pts were evaluable for response. Baseline characteristics of the ITT population and efficacy data are listed in the Table. Median follow-up was 14.6 months. Grade 3/4 adverse events occurred in 39% of pts, including leukocytopenia (11%), gastrointestinal toxicity (11%), and rash (9%). Median PFS was 9.6 months (95% CI: 5.0 to 14.1). QoL data will be presented. Conclusions: This pre-specified interim analysis supports efficacy and safety of biweekly cetuximab given in combination with mFOLFOX6 in pts with mCRC. A high rate of objective responses and secondary hepatic resections was achieved. Based on these results enrolment in CEBIFOX is continued. Clinical trial information: NCT01051167. [Table: see text]
Evaluation of variables that may impact chemotherapy (CT) administration after determination of <i>Onco</i>type DX (ODX) recurrence score (RS).
Authors: Kristina E. Bowen, James W. Gilmore, Stephen Szabo, Sally Haislip, Robert Hassell, Joseph Cooper, Steve Richardson, Meghan Fitzgerald, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2012)

571 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed lower than expected use of CT in patients (pts) with estrogen receptor-positive early-stage breast cancer (ESBC) at high-risk for recurrence by ODX RS. To better understand physician behavior, CHSS examined patterns of care in a large private practice oncology group with a robust EMR, Georgia Cancer Specialists (GCS). Pt characteristics and physician-prescribing patterns were analyzed to determine variables that most impacted the physician’s decision to treat high-risk pts with CT. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified pts with ESBC (stage I-II, node-negative, estrogen receptor-positive, HER2-negative) who underwent ODX testing. We determined the number of pts with a RS value in the low- (RS &lt;18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received CT in each category. The use of CT in high-risk pts was analyzed by pt age, tumor size, tumor grade, and physician prescribing patterns. Results: Of the 1908 pts identified with ESBC, 788 were eligible for ODX testing and 288 (37%) underwent testing. Fifty percent of pts were in the low-, 34% in intermediate-, and 16% in the high-risk groups. Six percent of low-, 41% of intermediate-, and 83% of high-risk pts received CT. In high-risk pts analyzed by age, CT was used in 100% of pts ≤ 45 years (y), 86% in pts 46-55 y, 86% in pts 56-65 y, and 25% in pts &gt;66 y. CT use in high-risk pts was 82% and 86% in pts with tumor sizes &lt;2 cm and 2-5 cm, respectively; and, 100%, 60%, and 91% in pts with grade 1, 2, or 3 tumors, respectively. Of the 41 physicians who were evaluated, 10 (24%) used ODX &lt;15% of the time, 13 (32%) used ODX 15-40%, 10 used (24%) used ODX 41-60%, and 8 (20%) used ODX &gt; 60% of the time. There were no significant differences in patterns of CT use. Conclusions: The less than expected use of CT in high-risk patients appears to be related to physician preference and pt age. Tumor size and grade did not appear to influence choice of therapy.
Association of prior pelvic radiation with long-term oncologic outcomes following radical cystectomy.
Authors: Harras B. Zaid, Matthew K. Tollefson, Igor Frank, William P. Parker, Robert Houston Thompson, Robert F. Tarrell, Prabin Thapa, John C. Cheville, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2017)

308 Background: Receipt of pelvic radiotherapy (PRT) prior to radical cystectomy (RC) has unclear association on oncologic outcomes. Methods: The Mayo Clinic Cystectomy Registry was queried to review 2139 patients undergoing RC for M0 bladder cancer between 1990 and 2010. We then identified patients receiving PRT prior to RC, and matched these cases to non-radiated controls (~1:2) on the basis of age, sex, receipt of neoadjuvant chemotherapy, and pathologic T and N stages. Cancer-specific survival (CSS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Of 2139 patients undergoing RC, 104 (4.9%) had received PRT prior to surgery. These patients were matched to 191 non-radiated control patients (no PRT). Overall, patients were well-matched on disease and patient characteristics. Median follow-up was 9.6 years (IQR 6.0, 14.8). During this time, 108 patients experienced disease recurrence and 218 died, including 122 who died from bladder cancer. Five-year CSS among patients who did versus did not receive PRT was 55% versus 63% (p=0.10), while the 5-year PFS was 55% versus 61% (p=0.32). Furthermore, the pattern of disease recurrence (abdominal/visceral, urothelial, local/pelvic, thoracic, soft tissue/other) did not differ between the no PRT and PRT groups (all p&gt;0.05). Conclusions: Receipt of PRT prior to RC is not associated with worse oncologic outcomes. While prior PRT may increase surgical complexity, CSS, PFS, and patterns of recurrence are similar to patients who have not received PRT.