tbuckley/cabot-search huggingface dataset:
Using information technology to power an integrated, community-based oncology palliative care model.
Authors: Dudley Gill, Andrew Allan Hertler, Lianne Matthews, RaeLynn Carr
Journal: Journal of Clinical Oncology (2016)

166 Background: There is a need to improve palliative care program access for patients with cancer. The identification of candidates for palliative care at the point of diagnose can improve care and reduce costs. This pilot program was launched in July 2015 by four stakeholders: Health plan; Regional palliative care provider; Community oncology practice; and Oncology quality management provider. Methods: Objectives are to increase patient satisfaction, reduce unnecessary utilization and costs. Data captured by information technology at the point-of-care are used to: Evaluate Diagnosis, Stage, Treatment Intent, Performance Status, and Line of Therapy criteria to identify patients with recurrent/metastatic disease who would potentially benefit from palliative care; Trigger a palliative care program referral; and Initiate the chemotherapy treatment preauthorization process. Retrospective analysis will evaluate: Patient (Concordance with goals &amp; cultural preferences, Member quality of care at end-of-life, Length of stay on hospice, Death in place of patient’s preference), Hospital (Deaths in acute/facility ICU), and Clinical (Referrals to palliative care and hospice; Use of chemotherapy 2 weeks prior to death). Results: See table below. Conclusions: There is an opportunity to inform physicians and oncology practice mid-level staff about the differences between palliative and hospice care. Community-based supportive care services can prevent avoidable hospital admissions. There have been two instances where having a palliative care nurse visit patients at their homes prevented hospital emergency department admissions. Educating patients about the benefits of palliative care can be challenging. For example, a patient with recurrent/metastatic breast cancer, an ECOG status of 2 and who had received beyond 4 th line treatment was not interested in the program. [Table: see text]
Cost-effectiveness of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for curatively resected gastric cancer
Authors: A. Hisashige, M. Sasako, T. Nakajima
Journal: Journal of Clinical Oncology (2008)

4578 Background: Evidence on the effectiveness of adjuvant therapy for gastric cancer has been limited. Recently, the ACTS- GC in Japan, a randomized controlled trial (n=1,059) of S-1 adjuvant therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery only. To evaluate value for money of adjuvant S-1 therapy, cost-effective analysis was carried out. Methods: Cost-effective analysis of adjuvant S-1 therapy, based on RCT, was carried out from a payer’s perspective, compared to surgery only. As an economic measure, cost per life-years (LYs) gained was estimated. Using patients’ data, overall survival was estimated by the Kaplan-Meier method, up to 4.7 years from randomization. Beyond this observation period, it was simulated by cure and competing risk models. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses of important factors were done. Results: For 4.7 years observation, adjuvant S-1 therapy gained 0.27 LYs and increased costs by $3,378 per person compared to surgery only (no discounting). For 10-year follow-up, it gained 0.70 LYs and increased cost by $2,762 per person. On the other hand, over lifetime, it gained 2.07 LYs and increased costs by $2,703. The incremental cost-effectiveness (ICE) ratio (95% confidence intervals) for 4.7 years observation was estimated to be $14,051 ($6,232, $81,190) using the bootstrap method (3% discount rate for both effect and costs). ICE ratios, for 10 years follow-up and over lifetime, were $4,893 and $1,996, respectively. Cost-effectiveness acceptability and net benefit analyses showed the robustness of these results. Conclusions: Adjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. Its cost-effectiveness is favorable compared with other interventions in oncology. Therefore, adjuvant S-1 therapy can be accepted for wide use. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Taiho
Do breast cancer treatment and imaging providers follow hereditary breast and ovarian cancer risk screening guidelines?
Authors: Christine B. Weldon, Julia Rachel Trosman, Melissa A Simon, Danielle Dupuy, Betty Roggenkamp, William John Gradishar, Anne Marie Murphy
Journal: Journal of Clinical Oncology (2014)

e17626 Background: Women with personal or family history suggestive of susceptibility to hereditary breast or ovarian cancer (HBOC) should be referred to genetic assessment (USPSTF, Ann Intern Med. 2005). Women with HBOC have a 50-85% lifetime risk of breast cancer, 30-50% of breast cancer before 50 years old,15-50% lifetime risk of ovarian cancer, and 40-60% chance of developing a second breast cancer (ASCO Cancer.net HBOC 8/2013). Our goal is to examine if this almost decade old guideline is followed in breast cancer treatment and breast cancer imaging centers in a large metropolitan area. Methods: We conducted an IRB approved web survey of all 35 breast cancer treatment sites (5 academic, 21 community, 9 public or safety net) and 58 breast imaging sites (5 academic, 27 community, 26 public or safety net) in Chicago. Results were analyzed using simple frequencies and Fisher's exact test. Results: We achieved a response rate of 91% (32/35 treatment sites, 53/58 imaging sites). We found that 56% (18/32) of treatment sites have a hereditary cancer syndrome (HBOC) screening process for newly diagnosed breast cancer patients. Most of these sites, 83% (15/18), always use genetic test results in surgical decisions, as compared to 21% (3/14) of sites that do not have an HBOC screening process, p=0.0009. Only 8% (4/53) of breast imaging sites have an HBOC screening process and provide indicated patients genetic assessment information and/or referrals. While 38% (20/53) of imaging sites conduct daily internal staff discussions of hereditary risk, only 15% of them (3/20) provide genetic assessment information to indicated patients. We found no statistically significant difference between practices of academic, community, public and safety net sites. Conclusions: Breast cancer treatment sites have partial adherence to HBOC risk screening guidelines; while breast imaging sites rarely adhere to HBOC risk assessment guidelines. Consistent HBOC risk screening protocols are needed in breast cancer treatment and breast cancer imaging sites that include providing indicated patients information about, and access to, genetic assessment.
Intensity-modulated radiation therapy (IMRT) for advanced oropharyngeal carcinoma: The MSKCC experience
Authors: F. F. de Arruda, J. Zhung, A. Narayana, S. Wolden, D. G. Pfister, V. Serrano, D. H. Kraus, A. Shaha, J. Shah, N. Y. Lee
Journal: Journal of Clinical Oncology (2005)

5513 Background: Retrospective review of an institution’s experience using IMRT for advanced oropharyngeal carcinoma. Methods: Between 9/98 and 6/04, 43 patients with oropharyngeal cancer underwent definitive IMRT at our institution. The disease was stage III in 7 (16%), and stage IV in 36 (84%) patients. Concurrent chemotherapy (CT) was used in 95% and consisted of planned 2–3 cycles every 3–4 weeks of cisplatin (100 mg/m2 IV in 71%), or carboplatin/5-fluorouracil (70 mg/m2/day IV and 600 mg/m2/day continuous infusion, both for 4 days, in 29%). Patients were treated using 2 different IMRT approaches: 74% Dose Painting and 26% Concomitant Boost (CB). The prescription dose to the gross tumor was 70 Gy. Feeding tubes (PEGs) were placed before treatment in 91% of the patients. Acute toxicity and late xerostomia were graded according to the RTOG radiation morbidity scoring criteria. Other complications were evaluated using subjective criteria such as the presence of esophageal stricture and the need for PEG usage. The local (LPF), regional progression-free (RPF), distant metastases-free (DMF) rates, and overall survival (OS) were calculated using Kaplan-Meier method. Median follow-up was 15.2 months (range 5.8–74). Results: The 2-year estimates of LPF, RPF, DMF and OS were 97.2%, 85%, 72.4% and 100% respectively. Two patients required a RT treatment break. The worst acute mucositis experienced were Grade 1 in 2 (5%), Grade 2 in 22 (51%), and Grade 3 in 19 (44%) patients. Xerostomia decreased with time and among the patients (22) with at least 9 months of follow up there were 68% of Grade 0–1 and 32% of Grade 2 toxicity. Of the 39 patients who required upfront PEG placement, 6 were still using PEGs for nutrition at the time of this analysis. Two patients had cervical esophageal strictures: one was still PEG dependent 1 year post treatment, and the other required routine esophageal dilatations. Both were treated using CB. There was no difference in the time to end PEG nutrition between both IMRT groups (p=0.9). Conclusions: In these preliminary results, IMRT achieved encouraging local control rates in patients with advanced oropharyngeal carcinoma. Treatment toxicity was acceptable in the setting of concomitant CT. No significant financial relationships to disclose.
A phase II study of capecitabine, carboplatin, and bevacizumab for metastatic or unresectable gastroesophageal junction and gastric adenocarcinoma.
Authors: Pamela L. Kunz, Prachi Nandoskar, Michael Zach Koontz, Hanlee Ji, James M. Ford, Raymond R. Balise, Aya Kamaya, Daniel Rubin, George A. Fisher
Journal: Journal of Clinical Oncology (2014)

115 Background: Gastroesophageal junction (GEJ) and gastric adenocarcinomas constitute a major health problem worldwide. In the United States, the incidence of adenocarcinoma of the esophagus, GEJ and gastric cardia is rising rapidly. Chemotherapy for metastatic disease improves survival and quality of life when compared to best supportive care. The addition of bevacizumab to chemotherapy in a large, randomized, multinational study showed conflicting results. Methods: Patients (pts) with biopsy proven metastatic or unresectable GEJ and gastric adenocarcinomas received bevacizumab 15 mg/kg IV and carboplatin AUC 6 IV on day 1 and capecitabine 850 mg/m 2 twice daily by mouth on days 1-14 on a 21-day cycle. Pts with stable disease (SD) or partial response (PR) were allowed to continue therapy with bevacizumab with or without capecitabine. Primary endpoints were progression free survival (PFS) and toxicity; secondary endpoints were overall survival (OS) and response rate by RECIST. Results: Between April 2009 and April 2013, a total of 35 pts were enrolled. At present, 29 patients are off treatment and 6 are still actively receiving treatment. 29 pts are available for response assessment, 6 patients came off study prior to their first tumor assessment. Baseline characteristics are: M:F = 25:10; median age = 58 years (range 25-81); primary site = GEJ (17) and gastric (18); degree of differentiation = well (3), moderate (12), poor/signet ring (18), and unknown (2); race = White Non-Hispanic (24), White Hispanic (6), and Asian (5). The 1-year PFS is 21% and median PFS is 8.5 months. Median OS is 14.3 months. Best response by RECIST is as follows: PR in 17 pts (49%), SD in 6 pts (17%), and progressive disease (PD) in 6 pts (17%). The treatment was well-tolerated with toxicities as expected. Conclusions: The combination of capecitabine, carboplatin and bevacizumab in metastatic or unresectable unresectable GEJ and gastric adenocarcinomas is well tolerated and shows promising response rates, though did not meet the primary endpoint of PFS. Clinical trial information: NCT00780494.
Surgery of residual disease following imatinib mesylate in advanced gastrointestinal stromal tumors (GIST)
Authors: A. Gronchi, M. Fiore, R. Bertulli, M. Colecchia, E. Tamborini, S. Pilotti, A. Messina, P. Coco, S. Stacchiotti, P. G. Casali
Journal: Journal of Clinical Oncology (2005)

9038 Background: To retrospectively analyze the outcome of advanced GIST patients undergoing surgery of residual disease after a period of Imatinib mesylate therapy. Methods: We reviewed patients with advanced GIST who received Imatinib mesylate within a EORTC-STBSG led intergroup trial, or within a Southern European Phase II study, or as a standard of care, and were subsequently operated on at the Istituto Nazionale Tumori, Milano, Italy, between July 2002 and September 2004. Group A patients were operated on while in response; Group B patients after primary or secondary progression. A total of 25 patients were identified, with a median follow-up of 18 months. Median duration of Imatinib therapy before surgery was 17 months. Mutational status is presently available for 14 patients (48%). Results: In Group A patients (n = 19), all were found to have remnants in the abdominal cavity/liver, with a variable proportion of viable cells at pathologic examination, irrespective of radiologic PR or CR. All biomolecularly assessed patients carried an exon 11 mutation (1 patient along with a coexisting acquired exon 13 mutation), except one wild-type. After a median follow up of 19.9 months, all patients are alive, 16 patients (84%) with no evidence of progression (all continued Imatinib after surgery), while 3 patients failed at 16–18 months (2 of them had discontinuated Imatinib). In Group B (n = 6), all patients had viable disease at pathologic examination. Amongst assessed patients, 25% showed an exon 9 mutation, and 75% an exon 11 mutation (1 patient with an acquired concomitant exon 14 mutation). All patients failed after a median of 6 months, 4 are alive and 2 died of disease at 3 and 10 months after surgery. Conclusions: Also this series suggests not to discontinuate Imatinib therapy after surgery of residual disease, even if complete. The prognostic advantage from surgery of residual disease in response is left to elucidate by combining available series. On the other hand, patients with progressive disease are candidates for second-line molecular-targeted therapies, surgery being likely of minimal benefit. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Adjuvant sequential chemo-radiation therapy in high-risk endometrial cancer: Results of a prospective, multicenter phase II study of the NOGGO.
Authors: D. Koensgen, A. Belau, J. Sehouli, H. L. Sommer, K. Bartz, S. Markmann, L. Schneidewind, J. P. Scharf, M. Ehmke, D. Stengel, P. Ledwon, H. Guba, M. Zygmunt, G. Koehler, A. Mustea
Journal: Journal of Clinical Oncology (2011)

5109 Background: To determine the toxicity, tolerability and quality of life (QoL) of adjuvant CT with sequential RT in patients (pts) with high-risk endometrial cancer (hrec). Methods: Pts with hrec from 8 institutions were enrolled. All pts underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic (100%) and paraaortic (77%) lymphadenectomy and surgical staging. Pts received four cycles of Paclitaxel 175 mg/m² (P) and Carboplatin AUC5 (C) (d1, q21d), subsequent external pelvic radiation therapy (45 Gy: 1.8 Gy/d) and vaginal brachytherapy (15 Gy: 3x 5 Gy). QoL was assessed using the EORTC-QLQ-C30 questionnaire. Primary endpoints: tolerability, toxicity and QoL. Secondary endpoint: progression-free survival (PFS). Results: Thirty-five pts were enrolled from December 2004 through May 2008. Median follow-up was 21 months (range, 3-24 months). Most of the pts (n=30) had an endometroid histology. Distribution of tumor stage (FIGO 2006) was: Ic:9, IIa:2, IIb:5, IIIa:3 and IIIc:16. All pts received 4 cycles of P and C. All pts completed RT. Grade 3/4 hematologic toxicities (in % of all cycles) were mild: leucopenia 6.6%, granulocytopenia 5.9%. Three cycles were delayed because of leucopenia. Darbepoetin alfa was given in 5.1%, G-CSF in 2.9%, blood transfusions in 2.9%. Grade 3/4 non-hematologic toxicities were seldom (< 3%). Only, alopecia occurred in 44.8%. No overall change in QoL occurred during treatment. Median Global Health Score was 50%. 2-year progression-free survival was 77.1%. Conclusions: Adjuvant combination CT with P+C and sequential RT is well tolerated and a feasible regimen in pts with hrec.
Use of insulin-like growth factor (IGF) pathway polymorphism IGF1R_rs2016347 to predict tumor recurrence in estrogen receptor–positive breast cancer patients.
Authors: T. Winder, G. Giamas, W. Zhang, D. Yang, P. O. Bohanes, Y. Ning, A. Gerger, M. J. Labonte, J. Stebbing, H. Lenz
Journal: Journal of Clinical Oncology (2011)

538 Background: Accumulating evidence suggests that insulin-like growth factor (IGF) signaling is an important pathway for breast cancer pathogenesis which regulates both cellular proliferation and apoptosis. Recently, IGF1 receptor (IGF1R) expression has been correlated and functionally linked with estrogen receptor (ER) signaling in breast cancer. We tested whether functional germline variations in the IGF-pathway are associated with clinical outcome in ER positive primary invasive breast cancer patients, who were treated with surgery and adjuvant hormone treatment. Methods: Tissue samples of 222 patients with ER positive primary invasive breast cancer, who had undergone surgery at Charing Cross Hospital, London, UK between 1981 and 2003, were analyzed. gDNA was extracted from formalin fixed paraffin embedded (FFPE) tissue samples and six (IGF1_rs6214, IGF1_rs2946834, IGF1_rs7136446, IGF1R_rs2016347, IGFBP3_rs2854744, IRS1_rs1801123) functional IGF1-pathway polymorphisms were analyzed using direct DNA-sequencing and PCR-RFLP. Results: In univariate analysis patients with primary invasive breast cancer carrying at least one T allele (GT or TT) of IGF1R_rs2016347 polymorphism had a significant better disease free survival (DFS) than patients with GG genotype (DFS 5.3 years versus 7.6 years; p=0.02). This association remained significant in multivariate analysis adjusting for tumor size, lymph node involvement, and c-erbB2 status [HR=0.57 (CI 95%; 0.36-0.9); adjusted p=0.01). The other tested IGF-pathway polymorphisms did not show significant associations for DFS. Conclusions: These results indicate functional IGF1R_rs2016347 polymorphism as independent prognostic marker for tumor recurrence suggesting that co-targeting both ER and IGF1R holds promise for the treatment of patients with ER positive breast cancer.
Evaluation of the association between tagging polymorphisms of the MACC1 locus and overall survival in patients with colorectal cancer.
Authors: A. Lang, S. Geller-Rhomberg, T. Winder, B. L. Hartmann, K. Gasser, B. Kohler, I. Grizelj, N. Stark, P. Tschann, H. Drexel, A. Muendlein
Journal: Journal of Clinical Oncology (2011)

3594 Background: The newly discovered metastasis-associated in colon cancer-1 (MACC1) gene is a key regulator of the HGH/met pathway. Deregulation of HGH/met signalling is reported as prognostic marker for early stage invasion, tumorigenesis, and metastasis. High expression levels of MACC1 have been associated with colon cancer metastasis and reduced 5-year survival. Potential links between the genetic diversity of the MACC1 locus and overall survival are unknown. We therefore investigated the association between MACC1 tagging single nucleotide polymorphisms (SNPs) and overall survival in a large cohort of colorectal cancer patients. Methods: The study included 319 subjects with histopathologically proven colorectal cancer at the Academic Teaching Hospital Feldkirch, Austria. Survival data were provided by the federal agency for statistics in Austria. Genomic DNA was isolated from formalin-fixed paraffin-embedded specimens; six tagging SNPs (rs1990172, rs3114446, rs10275612, rs3095007, rs3095009, and rs7780032) capturing the common variants of the MACC1 locus were genotyped by SNaPshot assays. Results: Over a mean follow up period of 4.3 (± 1.0) years, 73 deaths were recorded. Carriers of the rare allele of SNP rs1990172 showed a significantly decreased overall survival (HR = 1.73 [1.08 –2.77]; p = 0.023). Multivariate analysis adjusted for age, gender, and UICC tumor stage confirmed this result (HR = 1.82 [1.13 –2.94]; p = 0.013). Other investigated genetic variants of the MACC1 gene were not significantly associated with overall survival (p-values > 0.05). Conclusions: For the first time, our study investigates the influence of MACC1 tagging polymorphisms on overall survival suggesting SNP rs1990172 as a predictor for reduced overall survival in colorectal cancer patients. Further studies will be required to validate our findings.
Can skin/eye toxicity be used as a biomarker for dose selection of FDA approved Anti-EGFR agents?
Authors: Y. A. Men, P. Mummaneni, H. Zhao, S. Amur, J. Lee, L. Kenna, F. Frueh, N. A. Rahman, S. Huang
Journal: Journal of Clinical Oncology (2008)

14696 Background: Epidermal growth factor receptor (EGFR) is an attractive target for anti-cancer agents, which have shown activity against various types of tumors. Skin/eye toxicity is a class adverse effect associated with anti-EGFR therapy. This project aims to determine whether skin/eye toxicity can be used as a biomarker for dose selection of anti-EGFR agents. Methods: Extract information on dose and skin/eye toxicity from datasets of FDA approved anti-EGFR agents; Tabulate the percentage of subjects with skin/eye toxicity and perform sigmoidal Emax modeling to estimate the dose associated with maximum skin/eye toxicity; Compare the model estimated dose and the label recommended dose; Determine the capability using skin/eye toxicity as a measure for dose selection for anti-EGFR agents. Results: Skin/eye toxicity data were obtained from all six FDA approved anti-EGFR agents. The sigmoidal Emax model fit the data from trials of Drug A, Drug B and Drug C well, and the predicted dose matched the label recommended dose. Although the model fit the data for Drug D, the dose derived from the model was greater than the label recommended dose. The sponsor selected a lower dose to avoid toxicity related to pulmonary function for Drug D. Analysis of data on Drug E and Drug F did not predict the dose approved in the label. Drug A, Drug B and Drug C are specific inhibitors of the EGFR target, suggesting a mechanistic basis for the ability to predict their dose via sigmoidal Emax modeling of skin/eye toxicity data. Likewise, Drug D, Drug E and Drug F are known to interact with multiple tyrosine kinase pathways, and may explain why a simple sigmoidal Emax model did not predict their dose. Conclusions: Skin/eye toxicity may be used as a biomarker for dose selection for pivotal trials of anti-EGFR agents with high specificity for EGFR. More sophisticated modeling and additional data may be needed to determine how to predict the dose for less specific anti-EGFR agents. No significant financial relationships to disclose.