tbuckley/cabot-search huggingface dataset:
Multidisciplinary high-risk program: A community hospital’s experience.
Authors: H. Lowry, N. Dekhne, D. Fend, R. Lerman, N. Gregory, J. Boura
Journal: Journal of Clinical Oncology (2011)

1562 Background: Women are seldom offered breast cancer risk assessment and information regarding risk reducing interventions at the time of their annual physical examination. Routinely assessing risk during mammography could identify women at high risk (HR) of breast cancer (BC). The Beaumont Risk Assessment Questionnaire (BRAQ) was implemented in 2009 as a way of improving identification of HR individuals. This study evaluates our overall experience with this process. Methods: Upon IRB approval, women ages 35-85 presenting for their annual screening mammogram were offered the BRAQ by a mammography tech. This questionnaire included the Modified Gail Risk Model (GM) and yes/no questions regarding family history and prior chest wall radiation. Women with a GM lifetime risk ≥ 20% or the presence of any noted risk factors were determined to be HR. These individuals were offered referral to our High Risk Program (HRP) for close surveillance and risk management. The primary care physician was noted of the risk assessment by the radiologists as part of the mammogram results. The HRP was designed to provide a multidisciplinary approach for management and long term follow up of these HR women. A retrospective data review was conducted on 5,878 women (males were excluded) from three imaging locations from September 2009 to August 2010. Results: A total of 5,878 women agreed to complete the BRAQ. There were 5353 women completing enough information to determine lifetime GM. 17.2% (922) were found to be HR. At two of our three locations, a significant number declined participation (up to 34.2%). Mean age of participants was 55+/-11, 84.9% (4990) were Caucasian, 6.8% (400) were African American and 8.2% (487) were of other ethnicities. Of all 5878, 0.9% (53) women had undergone prior chest radiation. 46% (2678) had at least one first degree relative with BC. 4% (217) had a male relative with BC, 22%(1271) had 3 or more BC on one side of their family, 33% (1960) had a BC and ovarian cancer on one side, and 11% (677) noted 2 BC’s on the same side with onset under age 50. Conclusions: Identification of women at risk for BC is an integral component of comprehensive breast care. Our experience proves that this identification can be easily incorporated into a screening mammography visit.
Reversion of <i>BRCA1/2</i> Germline Mutations Detected in Circulating Tumor DNA From Patients With High-Grade Serous Ovarian Cancer
Authors: Elizabeth L. Christie, Sian Fereday, Ken Doig, Swetansu Pattnaik, Sarah-Jane Dawson, David D.L. Bowtell
Journal: Journal of Clinical Oncology (2017)

Purpose Germline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC. Patients and Methods Plasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were ascertained: patients with a malignancy before undergoing primary HGSC debulking surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and plasma samples were available for most patients (24 of 30). Targeted amplicon, next-generation sequencing was performed using primers that flanked germline mutations, whose design did not rely on prior knowledge of reversion sequences. Results Five patients were identified with intragenic mutations predicted to restore BRCA1/2 open reading frames, including two patients with multiple independent reversion alleles. Reversion mutations were only detected in tumor samples from patients with recurrent disease (five of 16) and only in cfDNA from patients with a tumor-detected reversion (three of five). Findings from a rapid autopsy of a patient with multiple independent reversions indicated that reversion-allele frequency in metastatic sites is an important determinant of assay sensitivity. Abundance of tumor-derived DNA in total cell-free DNA, as measured by TP53 mutant allele frequency, also affected assay sensitivity. All patients with reversions detected in tumor-derived DNA were resistant to platin- or poly ADP ribose polymerase inhibitor-based chemotherapy. Conclusion Reversion mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical utility for predicting chemotherapy response in recurrent HGSC.
Experience with IL-2 in metastatic renal cell carcinoma after treatment with one or more targeted therapies.
Authors: Hanh P. Mai, Peter Vu, Arjune Patel, Joseph Clark, Elizabeth Henry
Journal: Journal of Clinical Oncology (2016)

622 Background: Over half of patients (pts) diagnosed with Renal Cell Carcinoma require systemic therapy for metastatic disease (mRCC). Approved first line treatment includes immunotherapy and targeted therapy (TT). TT is commonly used given its efficacy, favorable side effect profile, and convenience of oral administration. High dose IL-2 (HD-IL2) can induce durable long term remissions in a subset of pts. There is limited data on the efficacy of HD-IL2 after disease progression on TT. Methods: All pts treated with HD-IL2 for mRCC from 2008-2014 were reviewed. A focused analysis was performed on pts who received HD-IL2 after first-line TT. Three pts were excluded from analysis. Data regarding pt demographics, health status, disease related characteristics, prognostic factors, treatment history and toxicity were captured. Response to HD-IL2 was also classified using RECIST definition. Utilizing descriptive statistics, we examined response rates, toxicities, and outcomes in this subset of pts. Results: Eighteen pts received HD-IL2 after TT. Median age was 60 (range 48-72). Six pts had primary mRCC and 12 had recurrent mRCC. Twelve pts received HD-IL2 as a 2nd line of treatment. Six pts received HD-IL2 as a 3rd or higher line of treatment. Among pts treated with HD-IL2 as 2nd line, 8 pts (67%) had partial response and 1 (8%) had complete response; duration of response ranged from 5-20+ months and 3 pts remain in remission. All 6 pts treated as 3rd line or higher did not show objective response to HD-IL2. The 2nd line group received significantly more doses than pts treated as 3rd line or higher (mean doses, 37 vs. 18, p=0.01). Overall, adverse events were expected, with the exception of grade 4 cardiac toxicity in 2 pts who received HD-IL2 as 3rd line. Conclusions: The administration of HD-IL2 as 2nd line is tolerated without excess toxicity and can induce clinical response. In our sample, there was no response to HD-IL2 among pts who received two or more prior TT. More investigation is warranted to determine if 3rd line HD-IL2 is safe and retains clinical benefit.
Identification of the androgen-induced transcriptional program of human prostate cancer revealed by causal analysis
Authors: K. O. Elliston, D. Pratt, W. Hahn, P. Febbo
Journal: Journal of Clinical Oncology (2005)

4637 Background: The transcriptional program induced by androgen stimulation in prostate cancer leads to increased cell proliferation. A better understanding the signaling pathways that are stimulated by androgen may identify new intervention points that can delay or prevent the progression of prostate cancer into an androgen resistant mode. Methods: Gene expression profiling was used to identify gene expression state changes between androgen stimulated and control LNCaP cells. Causal analysis of these state changes using a detailed, LNCaP specific biological network model containing 56,893 nodes and 154,440 connections was performed, and used to identify the signaling pathways that link androgen receptor to cell proliferation in this system. Results: Causal analysis of the gene expression state changes induced by androgen stimulation (R1881) of LNCaP cells implicated RB1 phosphorylation as the key proximal regulator of cell proliferation through a decrease in its transcriptional repressor activity, and through the stimulation of the E2F family of transcription factors. In addition, the stimulation of genes involved in fatty acid synthesis were observed, and could be explained by the activation of the SREBF family of factors through the activity of SCAP. Through extensive bottom-up modeling, it was possible to identify a network of signaling pathways that could control both SCAP activation of SREBF and phosphorylation of RB1 through the activation of androgen receptor (AR). These putative signaling pathways are being interrogated through RNAi to determine which pathways are predominately used to control cell proliferation in the LNCaP system. Conclusions: Causal analysis and modeling provides a valuable tool for the analysis of molecular profiling data, and when combined with experimental perturbations, can identify distinct mechanisms of action and can be used to design downstream experiments to probe these mechanisms. This study demonstrates the utility of detailed causal modeling and biological network analysis in the study of cellular models of prostate cancer, and portends the broad application of this systems approach to identifying the molecular mechanisms of cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genstruct Genstruct Genstruct
Pediatric and young adult (&lt;21) non-metastatic nasopharyngeal carcinoma (NPC) patients treated with neoadjuvant cisplatin and docetaxel (CD) chemoradiotherapy with plasma EBV DNA quantification
Authors: A. Varan, E. Özyar, M. Gültekin, F. Çorapçıoğlu, Y. Köksal, B. Aydın, C. Akyüz, M. Büyükpamukçu
Journal: Journal of Clinical Oncology (2008)

21003 Background: Evaluate treatment results of the pediatric and young adult (< 21 year of age) patients with non-metastatic nasopharyngeal carcinoma (NPC) who were treated with neoadjuvant cisplatin + docetaxel (CD) and radiotherapy. Patients and Methods: Ten patients with NPC diagnosed between 2004–2007 have been treated with four cycles of CDDP 100 mgr/m2 + docetaxel 75 mg/m2 on day 1 with premedication every three weeks. Radiotherapy doses were 60 Gy to the primary tumor and positive lymph node regions and 40 Gy supraclavicular field by shielding the clavicules. Five children was monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy and at follow-up. Results: Median age of the patients was 14 (9–20) with a male/female ratio of 6/4. Stage distribution was as follows: 2 with stage IIb, 2 with stage III, 4 pts with stage IVa, and 2 with stage IVb. One patient had a near complete response, 5 had partial response, and 3 had stable disease after CD chemotherapy and 1 progressed during CD chemotherapy. Over all survival rate in our protocol was 90%, whereas event free survival rate was 80%. No major chemotherapy toxicity was observed. EBV DNA titers were higher levels in two out of five patients at the time of diagnosis. Conclusion: Cisplatin+docetaxel combination was safe and effective in childhood nasopharyngeal carcinoma. There were no major toxicity during the chemotherapy. Plasma EBV DNA is useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment. No significant financial relationships to disclose.
Compliance to adjuvant hormone therapy for black and white women with breast cancer.
Authors: S. Bhatta, N. Hou, D. Huo, B. N. Polite, G. F. Fleming, O. I. Olopade, S. Hong
Journal: Journal of Clinical Oncology (2011)

1555 Background: The use of adjuvant hormone therapy for estrogen receptor positive (ER+) breast cancer significantly decreases breast cancer recurrence and mortality. For reasons that are poorly understood, black women have lower risk but higher mortality from breast cancer. To better understand factors contributing to the disparate outcomes, we examined differences in compliance to adjuvant hormone therapy by race/ethnicity in women treated for ER+ breast cancer at a private University medical center. Methods: 381 women with ER+ breast cancer 2 to 10 years from their initial diagnosis identified from a University cancer center registry were asked to complete a mailed survey. Compliance to therapy was self-reported (see table). A proportional odds model was used to evaluate possible predictors of compliance including ethnicity, perceived risk for breast cancer recurrence, and perception of adjuvant hormone therapy importance on risk reduction. Multivariate models were used to adjust for age of diagnosis, education completed, income, and out of pocket expenses for prescription medications. Results: Among the 208 (55%) responses, black women had lower levels of therapy compliance compared to white women (adjusted odds ratio (OR) = 0.40, 95% CI: 0.19-0.83). Regardless of race, the most significant determinant of compliance was perception of hormone therapy importance in risk reduction (adjusted OR=1.58, 95% CI: 1.06-2.36). Other variables including age or fear of recurrence did not affect compliance. Conclusions: For both black and white women compliance to therapy is affected by perceived importance of treatment. This study underscores the need for more effective doctor-patient communication to improve adherence to adjuvant hormone therapy, especially among ethnic minorities. Study sample. n (%) White n=141 Black n=67 P value Age (mean; range) 57.9; 39-72 58.6; 42-73 0.4 > some college education 113 (80.4) 45 (67.7) 0.04 Income ≥60K 95 (67.3) 17 (25.3) <0.001 Reported therapy compliance Never took 4 (2.8) 5 (7.8) 0.005 Missed > 1/week 0 (0) 3 (4.7) Missed < 2x/month 11 (7.8) 4 (6.3) Missed ≤1 month 29 (20.6) 22 (32.8) Never missed dose 97 (68.8) 32 (48.4)
A phase II study of BAY 43–9006 in patients with androgen-independent prostate cancer (AIPC) with proteomic profiling
Authors: E. M. Posadas, J. Gulley, P. M. Arlen, N. Harold, S. Fioravanti, P. Meltzer, C. D. Scripture, W. D. Figg, E. C. Kohn, W. L. Dahut
Journal: Journal of Clinical Oncology (2005)

4762 Background: BAY 43–9006 (Sorafenib) is a bis-aryl urea with potent anticancer properties. It is a potent inhibitor VEGFR-2, Raf kinase and BRAFV599E. Accumulating evidence suggests that the Ras-Raf-MAPK-ERK signaling pathway is dysregulated in the setting of AIPC. Furthermore, published studies have shown a role for anti-angiogenic therapy for AIPC. We have launched a phase II study to determine the clinical and biological activity of BAY 43–9006 in patients with AIPC. Methods: Patients are enrolled in an open-label, single arm phase II study. They must have good performance status and normal end-organ function. Patients with uncontrolled hypertension and those requiring therapeutic anticoagulation are excluded. All patients are treated with orally administered BAY 43–9006 at a dose of 400 mg bid given continuously on 28-day cycles. Clinical assessment occurs every 28 days with radiographic measurements of disease every 2 cycles. Treatment continues until progression. Tissue and bone marrow biopsies are being collected for proteomic analysis using tissue lysate microarrays. The arrays will be used to quantitatively analyze alterations in molecular signaling in response to therapy and to correlate proteomic information (e.g. phosphorylation) with BRAF mutational status. Results: This study opened in September 2004 and 7 patients have been enrolled thus far. Six have completed at least 1 cycle of therapy. No grade 3–4 toxicities have been observed. Hypertension (grade 2) has been noted in 2/6 patients. Drug-related rash has been seen in 6/6 patients and has responded to temporary withdrawal of therapy. No hand-foot syndrome has been reported. Other grade 1 toxicities noted include fatigue, flatulence, weight loss, anorexia, body aches, bradycardia, and diarrhea. Four patients have been treated for at least 8 weeks; one has exhibited stable disease by both PSA and radiographic criteria. Conclusions: BAY 43–9006 appears to be well-tolerated in patients with AIPC with a reversible skin rash and hypertension as the most prevalent toxicities. Accrual continues to better assess the activity and the toxicity profile of this agent. No significant financial relationships to disclose.
Hematopoietic Cell Transplant Versus Chemotherapy As Consolidation Treatment for Pediatric AML with Poor-Risk Cytogenetics
Authors: Michael J. Kelly, John T. Horan, Todd A. Alonzo, Mary Eapen, Robert B. Gerbing, Wensheng He, Beverly J. Lange, Susan K. Parsons, William G. Woods
Journal: Blood (2012)
The role of ACOs in accelerating high-quality care: Implications for prostate cancer.
Authors: Grant Picarillo, Natasha Jivani, Colin Nash, Kristi Mitchell
Journal: Journal of Clinical Oncology (2012)

151 Background: Accountable Care Organizations (ACOs) seek to promote high quality, coordinated care by eliminating unnecessary procedures, sharing clinical information, and meeting quality targets. Of the 65 proposed quality measures outlined in the Medicare Shared Savings Program (MSSP), only two relate specifically to cancer care, calling into question how such models will accelerate high quality care in oncology. Prostate cancer offers an insightful case study as it is characterized by a lack of consensus around diagnosis and treatment and the involvement of several providers throughout the care continuum. Methods: As part of a multi-layered analysis to evaluate the impact of the ACO model on quality improvement and the management and treatment of prostate cancer, Avalere examined recent legislation (e.g., the Affordable Care Act, MSSP) to identify key characteristics of the model. Avalere then reviewed the potential impact of these characteristics in oncology by examining clinical guidelines and reviewing public statements by key opinion leaders. After identifying gaps specifically related to prostate cancer, Avalere categorized the characteristics into three groups based on their potential impact on prostate cancer care: high, moderate, and low. Results: Our analysis yielded the following categorization of the ACO characteristics: High Impact: Streamlined coordination of care between facilities and providers Focus on high-risk, high-cost populations Moderate Impact: Emphasis on preventative health Standardized use of outcomes-based quality measures Low Impact: Improved medication continuity Chronic disease management Shared savings incentives Conclusions: As providers involved in prostate cancer care explore the ACO concept, it will be critical to identify the characteristics with the greatest potential to improve the quality and coordination of care, and to incorporate these characteristics into the guideline recommendations influencing the standard of care. Our research indicates that prostate cancer guidelines should emphasize the low quality and high cost of fragmented care in this patient population and develop recommendations on proven methods of care coordination and quality improvement.
Global profiling of fecal and tissue mirnas in Asian Chinese colorectal cancer patients.
Authors: Lee Cheng Phua, Poh Koon Koh, Peh Yean Cheah, Eric Chun Yong Chan, Han Kiat Ho
Journal: Journal of Clinical Oncology (2013)

439 Background: Fecal miRNAs are increasingly explored as non-invasive diagnostic markers of colorectal cancer (CRC). However, a holistic understanding of the global fecal miRNA profile in CRC patients is lacking, particularly in Asian patients. Also, it remains to be determined if the fecal miRNA profile mirrors the tumor profile. Here, we assayed the global human fecal miRNAs in Asian Chinese CRC patients to elucidate relevant diagnostic fecal markers. The disease-related profiles between feces and resected tumor of matched patients were also compared. Methods: MiRNAs were extracted from the feces of sporadic CRC patients (stage B – C, n=8) and healthy subjects (n=8) recruited into the study from September 2011 – July 2012. MiRNA expression profile was analyzed on Agilent miRNA array (miRBase Release 16.0). Biopsied tumor tissue (n=8) and matched normal mucosae (n=8) from the same CRC patients were also analyzed. Results: Univariate tests uncovered novel fecal markers (p&lt;0.05) characterizing CRC (e.g. elevated miR-3619-5p and miR-4269; decreased miR-3164 and miR-3917), even though global fecal miRNA profiles did not differentiate CRC patients from healthy subjects. Fecal miR-223 was appreciably higher in CRC patients, corroborating with Caucasian studies. Tumor miRNA signature was clearly distinct from matched normal mucosa (PLS-DA Q 2 =0.883). Discriminating tumor miRNAs (p&lt;0.05) included previously unreported (e.g. miR-874 and miR-4290) and known oncogenic miRNAs (e.g. miR-17-92 cluster and miR-135b) in the context of CRC. Notably, the global fecal miRNA profile was markedly different from that of tissue, suggesting that miRNA aberrations within CRC tumor did not significantly influence the fecal miRNA profile. Conclusions: A global profiling approach identified novel sets of differentially expressed miRNAs at the fecal and tissue level that may complement existing diagnostic markers and provide new insights into CRC pathogenesis. Interestingly, dysregulated miRNAs in the feces were different from the tumor, suggesting the presence of other contributors to the fecal miRNA profile. There is a need to reconsider using tissue biomarkers indiscriminately in different biological matrices.
The Singapore liver cancer recurrence (SLICER) score for relapse prediction in patients with resected hepatocellular carcinoma.
Authors: E. Ng, S. Ang, H. Li, K. Lim, S. Choo, J. Y. Ngeow, H. Toh, P. K. Chow, M. Tan
Journal: Journal of Clinical Oncology (2011)

169 Background: Hepatocellular carcinoma (HCC) is a common worldwide cancer associated with extremely poor survival, with surgery the only option for cure in patients with localized disease. Current prognostic models for HCC are algorithms developed on datasets of mainly patients with metastatic or unresectable cancer, and may be less relevant to resectable HCC. Nomograms provide individualized outcome estimates. We constructed a postoperative nomogram, the Singapore liver cancer recurrence (SLICER) score, to predict outcomes of HCC patients who have undergone surgical resection. Methods: Records for Singaporean patients undergoing first-line curative surgery for localized HCC in one institution between 1992 and 2007 were retrospectively reviewed (n=405). Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation, was used. Calibration was tested with bootstrapping (n=200). We compared the performance of this model with other alternative models including CLIP, CUPI, BCLC, and Okuda scores using c-indices and likelihood analysis. Results: A nomogram (SLICER score) predicting FFR was designed, incorporating vascular invasion, tumor size, multifocality, ECOG status, pre-operative AFP, Childs-Pugh score and cirrhosis. Bootstrap estimates show good calibration at 1, 2, 3, and 5 years postsurgery Comparison of the SLICER score with alternative prognostic models shows superior performance (Table). Conclusions: The SLICER score enables individualized relapse predictions for patients following curative resection of localized HCC. It permits optimal patient selection for adjuvant therapy trials, biomarker development, and individual counseling. [Table: see text] No significant financial relationships to disclose.