tbuckley/cabot-search huggingface dataset:
Association of androgen receptor V9 (ARV9) mRNA expression in metastatic tissue with early resistance to pre-chemotherapy abiraterone acetate/prednisone (AA/P).
Authors: Manish Kohli, David W. Hillman, Rachel Carlson, Liguo Wang, Ying Li, Winston Tan, Thai Huu Ho, Hugues Sicotte, Liewei Wang, Brian Addis Costello, Henry C. Pitot, Fernando Quevedo, Roxana Stefania Dronca, Timothy Jerome Moynihan, Thomas D Atwell, Patrick W Eiken, Brendan P McMenomy, Alan Haruo Bryce, Kevin Wu, Scott Dehm
Journal: Journal of Clinical Oncology (2016)

237 Background: AA/P is an approved treatment for mCRPC but there are no known predictive markers of response or resistance. We conducted a prospective trial to evaluate if Androgen Receptor (AR) &amp; AR-variant (ARV) expression in tissue metastases can predict resistance to AA/P. Methods: mCRPC stage patients (pts) initiating pre-chemo AA/P underwent metastatic site biopsies prior to (pre-AA/P) and after 12 weeks of treatment. Composite progression at 12 weeks, (primary endpoint) was evaluated with PSA, RECIST, bone scan and symptoms (per PCWG2). mRNA expressions of pre-AA/P ARFL, ARV3, ARV7, ARV9, ARV23, ARV45, four cell cycle division genes, Chromogranin-A (CHGA) together with PSA/testosterone levels, Gleason Score (GS) at initial diagnosis; high versus low volume disease; time from starting hormone therapy to mCRPC stage and serum CHGA levels were evaluated using a logistic regression model for predicting resistance at 12 weeks of therapy. A final multivariate model fitted only those factors thought to be clinically relevant or with an entry threshold of p ≤ 0.3 in univariate analysis. Results: Between 6/2013 &amp; 3/2015, 82 pts were enrolled of which 52 had complete mRNA expression &amp; disease assessment data at the12-week time point for analysis. Median age of the cohort was 72.5 yrs (IQR: 68.5-78); median pre-AA/P PSA was 18 ng/ml (IQR: 8.1- 46.6); GS distribution at initial diagnosis for GS 2-6; 7; 8-10 was 11; 14; 27 respectively. Progression was observed in 21/52 pts after 12 weeks. At the univariate level elevated pre-AA/P expression of ARV3 (p = 0.08), ARV7 (p = 0.26), ARV9 (p = 0.04), and cell division cycle gene CDC45 (p = 0.19) along with GS at diagnosis (p = 0.29) met the threshold for inclusion into multivariate analysis. Elevated expression of pre-therapy ARV9 in metastases alone was associated with progression at 12 weeks (OR: 3.9; CI 1.07 – 14.16; C-Index: 0.63). The 12-week biopsy of pts with progression had increased ARV9 mRNA expression compared to pts responding at 12 weeks (p = 0.14). Conclusions: Increased ARV9 mRNA expression in metastases is associated with early resistance to AA/P. This observation will need further validation in comparable datasets. Clinical trial information: NCT #0195364.
Improved survival in patients with malignant pleural mesothelioma since 2003
Authors: M. Serke, N. Schoenfeld, J. Kollmeier, D. Kaiser
Journal: Journal of Clinical Oncology (2008)

19022 Background: In our chest hospital patients with malignant pleural mesothelioma (MPM) were treated since decades. We compare patients survival before and after the introduction of a new chemotherapy regimen (platinum/pemetrexed) 2003. Methods: Between 1990 and December 2007 we diagnosed and treated 338 patients with MPM, 278 males and 60 females. All patients were retrospectively analyzed. Standard treatment in our institution for patients with good performance status is palliative surgery with pleurectomy and decortication, followed by chemotherapy. Only few patients had extra pleural pleuropneumonectomy (EPP), followed by chemotherapy. Our therapeutic strategy has not changed in the last years. We divided our patients in 2 treatment groups: those with diagnosis before 2003 (group I: 250 patients) or a diagnosis of MPM since 2003 (group II: 88 patients). Since 2003 all patients were treated with the platinum/pemetrexed combination. Results: Median survival (Kaplan-Meier-method) of all patients, diagnosed between 1990 and 2007 was 462 days with a 1- year-survival of 60% and a 2-year-survial of 37%. Median survival of group I (250 patients, 16% censored) was 352 days, compared to 652 days in group II (72% censored) and has nearly doubled. 1-year surval increased from 58% (group I) to 90% (group II), as well as the 2-year- survival, which increased from 28% (group I) to 48% (group II). Median survival of the patients with combined surgery and chemotherapy group I (104 pat., 25% censored) increased from 522 days to 1,046 days in group II (46 pat., 82% censored). In the patient group treated only with chemotherapy, 1-year survival improved from 60% to 85% and the 2-year survival from 20% to 40%. Conclusions: The introduction of an effective chemotherapy regimen 2003 with platinum/pemetrexed prolonged survival in patients with malignant pleural mesothelioma. This survival benefit was seen in multimodal treatment regiments as well in patients under chemotherapy alone. No significant financial relationships to disclose.
The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis
Authors: Viviana Palazzo, Aldesia Provenzano, Francesca Becherucci, Giulia Sansavini, Benedetta Mazzinghi, Valerio Orlandini, Laura Giunti, Rosa Maria Roperto, Marilena Pantaleo, Rosangela Artuso, Elena Andreucci, Sara Bargiacchi, Giovanna Traficante, Stefano Stagi, Luisa Murer, Elisa Benetti, Francesco Emma, Mario Giordano, Francesca Rivieri, Giacomo Colussi, Silvana Penco, Emanuela Manfredini, Maria Rosa Caruso, Livia Garavelli, Simeone Andrulli, Gianluca Vergine, Nunzia Miglietti, Elena Mancini, Cristina Malaventura, Antonio Percesepe, Enrico Grosso, Marco Materassi, Paola Romagnani, Sabrina Giglio
Journal: Kidney International (2017)
Survival benefit associated with the number of chemotherapy/biologic treatment lines in 5,129 elderly metastatic colon cancer patients.
Authors: Nader Hanna, Zhiyuan Zheng, Corinne Woods, Ebere Onukwugha, Kaloyan A. Bikov, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2013)

e14524 Background: Metastatic colon cancer (mCC) patients often receive multiple lines of chemotherapy/biologics treatment to improve survival, yet the "real world" benefits and risks of multiple treatment lines have not been fully examined. Methods: The National Cancer Institute’s SEER-Medicare data was analyzed to determine the association between the number of treatment lines and 5-year survival in mCC patients. Patients were at least 66 years old, diagnosed with mCC in 2003-2007 and followed until death or 12/31/09. Only patients who survived at least 3 months from diagnosis were included. Cox proportional hazards regression was used along with inverse probability weighting method to adjust for the probability of receiving treatment. Results: Of 5,129 elderly Medicare mCC patients, the 5-year survival rate was 12.9% (n=664). Each incremental treatment was significantly associated with an increase in the average five-year survival by 5.4 months, 7.2 months and 2.7 months for 1 st -line, 2 nd -line and subsequent treatments, respectively. Significant variables associated with increased mean survival times were receipt of 1 st -line, 2 nd -line or subsequent treatment compared to no treatment (hazard ratio HR=0.58, 0.36 and 0.32, respectively, p&lt;.01); resection/ablation of liver metastases (HR=0.80, p&lt;.01) and primary site surgery (HR=0.52, p&lt;.01). Significant variables associated with lower survival times were poorly-graded tumor (HR=1.53, p&lt;.01), Charlson Comorbidity Index score of at least 3 compared to 0 (HR=1.15, p=.016), female (HR=1.07, p=.043) and age (in 10-year increments, HR=1.06, p=.011). Conclusions: Among elderly Medicare mCC patients who survived at least 3 months from diagnosis, receipt of 1 st -line, 2 nd -line and subsequent treatments was associated with incremental increases in the average survival time. However, this may reflect physician treatment patterns in healthier patients who are more likely to receive treatment. Additional factors that significantly increased survival time were primary site surgery (by 5.5 months), resection/ablation of liver metastases (by 1.9 months) and a tumor not poorly-graded (by 3.6 months).
The development of a value-based pricing index for new drugs in metastatic colorectal cancer.
Authors: G. Dranitsaris, I. Truter, M. Lubbe
Journal: Journal of Clinical Oncology (2011)

6038 Background: Worldwide, prices for cancer drugs have been under downward pressure where several governments have mandated price cuts of branded and generic products. A better alternative to mandated price cuts would be the estimation of a launch price based on drug performance, cost effectiveness and a county’s ability to pay. In this study, the development of a global pricing index for new drugs that encompasses all of these attributes in patients with metastatic colorectal cancer (mCRC) is described. Methods: A pharmacoeconomic model was developed to simulate clinical outcomes in mCRC patients receiving standard chemotherapy with the addition of a “new drug” that improves survival by 1.4, 3 and 6 months respectively. Cost and health state utility data were obtained from cancer centers and oncology nurses (n=112) in Canada, Spain, India, South Africa and Malaysia. A price per dose was estimated for each survival increment using a target value threshold of three times the per capita GDP for each country, as recommended by the World Health Organization (WHO). Multivariable analysis was then used to develop the pricing index, which considers survival benefit, per capita GDP and income dispersion as measured by the Gini coefficient as predictor variables. Results: Higher survival benefits were associated with elevated drug prices, especially in wealthier countries such as Canada and Spain. For a nation like Argentina with a per capita GDP of $15,000 and a Gini coefficient of 51, the pricing index estimated that for a drug which provides a 4 month survival benefit in mCRC, the value based price would be $U.S.630 per dose. In contrast, the same drug in a wealthier country like Norway could command a price of $U.S.2,775 and still be considered cost effective according to the WHO criteria. Conclusions: We present a global pricing index that can be used to estimate a value based price in different countries for new drugs in mCRC. The application of this index to estimate a price based on cost effectiveness would be a good starting point for opening dialogue between the key stakeholders and a better alternative to governments’ mandated price cuts.
The prognostic implication of phosphoinositide 3-kinase/Akt pathway in gastric carcinomas.
Authors: Maria D. Begnami, Paula Chiappini, Wilson L. Costa Jr., José Humberto Fregnani, Felipe José Fernandez Coimbra, Alessandro Landskron Diniz, Clovis Pinto
Journal: Journal of Clinical Oncology (2012)

49 Background: The phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B, PKB) signaling pathway plays a critical role in cell growth and survival. Dysregulation of this pathway has been found in a variety of cancer cells. Recently, constitutively active PI3K/Akt signaling has been firmly established as a major determinant for cell growth and survival in an array of cancers. Blocking the constitutively active PI3K/AKT signaling pathway provides a new strategy for targeted cancer therapy. The purpose of our present study was to investigate the expression of activated mTOR (p-mTOR), PTEN, and pAKT in non-neoplastic gastric tissue and in gastric cancer patients to determine their pattern of expression in gastric tumors and their prognostic significance. Methods: The expression of p-mTOR, pAKT, and PTEN was detected in specimens of 239 gastric cancers who underwent radical resection (R0) and in 200 non-neoplastic gastric tissues by immunohistochemistry. Slides were scanned and analyzed with an automated cellular imaging system (ACIS III, Dako). The correlation of p-mTOR, pAKT, and PTEN expression to clinicopathologic features and survival of gastric cancer was studied. Results: Overexpression of pMTOR in the cytoplasmic pattern, nuclear pAKT, and nuclear PTEN was observed in the non-neoplastic tissues when compared with gastric tumor tissues (all, p&lt;0.001). Overexpression of pmTOR, pAKT, and PTEN in gastric tumors was closely correlated with pTNM stage (p&lt;0.001, p=0.008, p=0,036, respectively). Patients with p-AKT positive showed significantly longer disease-free survival (DFS) and overall survival (OS) rates than those with pAKT-negative tumors in univariable analyses. In multivariable analyses, higher expression rates of pMTOR and losses of PTEN were significantly associated with worse overall survival. Conclusions: Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the gastric carcinogenesis. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway for selected patients.
Establishing a system to monitor and evaluate the quality of cancer care in Japan.
Authors: Momoko Iwamoto, Fumiaki Nakamura, Takahiro Higashi
Journal: Journal of Clinical Oncology (2014)

287 Background: To ensure equitable access to high-quality cancer care, efforts to routinely measure key performance indicators of cancer policy began in Japan in 2014. Although assessing the quality of cancer care is a vital component of this initiative, a system for evaluating process of care across a large number of hospitals has not yet been established. We aimed to establish this system by creating a database of health claims data linked to hospital-based cancer registry (HBCR) and measuring quality indicators (QIs) for cancer care. Methods: We created a database of 28 months (Sept10-Dec12) of health claims data linked to HBCR for 100,825 breast, prostate, colorectal, stomach, lung, liver, and cervical cancer patients who were newly diagnosed in 2011 from 178 designated cancer care hospitals in Japan. Among 206 QIs that were previously developed by a panel of experts, we measured 13 that were measureable from claims data: 1) seven QIs on adherence to guidelines on adjuvant therapy, 2) four QIs on lab tests, procedures, and medication, and 3) two QIs on supportive care. Results: QIs investigating adherence to clinical guidelines on adjuvant therapy tended to be lower compared to QIs for supportive care. For example, 48.0% [46.4, 49.6] of stage III colorectal cancer patients (n=3,638) received adjuvant chemotherapy (5FU+LV, UFT+LV, Cape, FOLFOX, or CapeOX) within 8 postoperative weeks, whereas 68.1% [67.2, 69.0] of patients (n=10,104) received three-drug combination (5HT 3 -r antagonist, dexamethasone, and aprepitant) before receiving highly emetogenic chemotherapy. QIs on appropriate testing and procedures were higher overall, such that 83.3% [82.6, 84.0] of invasive breast cancer patients (n=12,447) received HER2 testing. In all QIs, there was large variability in performance across hospitals. Feedback was given to hospitals through interactive webpages. Conclusions: This is the first attempt at measuring the quality of cancer care across such a large number of hospitals in Japan. Our research showed that in all QIs, there was ample room for improvement. Continuous monitoring, improving feedback methods, expansion of QIs, and application of electronic health records, will be our next challenge as we move forward in this initiative.
Correlates of poor surgical margins following initial surgery for ductal carcinoma in situ and receipt of additional surgery.
Authors: M. E. Sorbero, J. J. Griggs, G. M. Ahrendt, L. M. Schiffhauer, A. Stark, A. W. Dick
Journal: Journal of Clinical Oncology (2011)

6087 Background: Poor margin status (positive or close margins) decreases 10-year event-free survival by up to 40% in women with ductal carcinoma in situ (DCIS). Nevertheless, poor surgical margins are common following initial breast conserving surgery (BCS), and not all women with poor margins have additional surgery to obtain negative margins. We identified factors associated with additional surgery in women who had BCS with close or positive margins and the type of surgery performed. Methods: Retrospective analysis of sociodemographic, clinical and surgical treatment data for women treated for DCIS from 1985 through 2000 who had poor surgical margins (close, i.e. 2 mm, or positive margins) after initial BCS (n=620, representing 684 surgeries). Patients were identified through two tumor registries and demographic, clinical, and treatment information were obtained through medical chart review. Detailed treatment and pathology information were obtained for each surgical procedure. Logistic regression models with physician fixed effects were performed to assess 1) which patients went on to have additional surgical treatments, and 2) among those women having additional surgery, what type of surgery was received (mastectomy or BCS). Results: 66.5% of women with poor surgical margins had additional surgery. While most had one additional procedure, 11.8% had more than one. The likelihood of additional surgery declined over time.Extent of DCIS was significantly associated with additional surgery when margins were poor. There was significant variation among surgeons in who had additional surgery for poor margins. 45% of the subsequent surgeries were re-excisions; the remaining mastectomies. A family history of breast cancer, extensive DCIS and unfavorable prognostic indicators were significant and positive predictors of mastectomy as the subsequent surgery. Surgeons did not have a significant effect on surgical treatment choice. Conclusions: Rather than focusing on surgical quality as determined by final margin status, these findings suggest that the decision to undergo additional surgery is influenced by other prognostic indicators and is driven, at least in part, by surgeons.
Germ line predictors of response to androgen deprivation therapy in men with advanced prostate cancer.
Authors: Neeraj Agarwal, Tyler Howard Buckley, Jim M. Farnham, Shiven B. Patel, Anitha Alex, Craig Teerlink, Frederick S. Albright, Robert A Stephenson, Lisa A Cannon-Albright
Journal: Journal of Clinical Oncology (2015)

162 Background: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict time to response to androgen deprivation therapy (ADT) in advanced prostate cancer, serve as prognostic and predictive biomarkers, and guide towards more individualized upfront therapy. Methods: 47 polymorphisms (PMs) in 22 genes involved in the androgen metabolic pathway were investigated using tagging SNPs for association with time to onset of castration resistance in 144 Caucasian men diagnosed with advanced prostate cancer undergoing ADT. Linear regression was employed using Gleason score as a covariate and assessing each SNP under one of three genetic models: 1) an additive model in which the number of minor alleles contributes increasing risk (or protection), 2) a dominant model in which the presence of 1 or 2 minor alleles have the same effect, and 3) a recessive model in which the presence of 2 minor alleles are necessary. Results: PMs in 3 genes (CYP1A1, HSD17B3, and HSD17B12) were significantly associated with time to prostate cancer recurrence after medical castration while controlling for Gleason Score. Table summarizes the genes found to be significantly associated with time to recurrence and the modes of inheritance considered. (Only SNPs found to be nominally significant (p &lt; .05) either with or without controlling for Gleason score in at least one model are shown.) Conclusions: In this preliminary report of ongoing work, germ line variations in multiple genes in the sex steroid hormone metabolic pathway predicted time to response to ADT, and warrant further validation to define their role as prognostic and predictive markers in this setting. [Table: see text]
Psychosocial distress screening in community oncology: A feasibility study.
Authors: Magdolna Solti, Tracy Webb, Joyce Koerber, Rosemary Mcdermott, Virginia Hill
Journal: Journal of Clinical Oncology (2016)

194 Background: Screening for psychosocial distress is an unmet need for cancer survivors. The oncology team has a critical role caring for the whole patient. We designed a comprehensive screening for newly referred patients in a community oncology setting. The purpose of our screening is early detection of moderate to severe distress and early intervention through social workers. Methods: This feasibility study included 292 newly diagnosed cancer and hematology patients entering our center between May 1 and July 31, 2015. Each participant completed the NCCN Distress Thermometer with checklist and PHQ-2 survey as part of the New Patient Questionnaire. The psychosocial team designed the triage process and contacted each patient if either the distress score or the PHQ-2 scores were ≥ 4. The screened patients underwent counseling by social work and were provided educational materials by nurse navigators and referred to community counselors as needed. Results: 67 % of the 292 newly diagnosed patients completed the screening tool. The average distress score was 4.31, and the average PHQ-2 score was 1.48. Based on the predefined criteria, 63% of all new patients reported significant distress. One-third of these patients had a distress score of 4, and were managed by nurse navigators. 63 patients with higher score were seen by social worker, 23 (37%) were referred to community counseling and 16 (25%) received ongoing follow-up. The documented need of psychosocial counseling increased by 28% during the program. By the end of the project period the early detection rate of severe depression (PHQ-2 ≥ 4) increased from 33% to 80%. The majority of the patients appreciated the distress screening, and the suggested coping strategies and support. Conclusions: Distress screening for newly diagnosed hematology and oncology patients is feasible in the community oncology setting. A large number of previously undetected patients with distress and depression were identified. The distress tool aided in early intervention and providing follow-up. The screening was also effective in identifying patients with high distress and in need to mitigate a crisis. Providing appropriate resources and referrals is essential to manage the extra workload on the psychosocial team.