tbuckley/cabot-search huggingface dataset:
Immunohistochemical breast cancer profile of women in the Brazilian Amazonia.
Authors: Danielle Feio da Costa, Juliana Passos Pereira, Ney PC Santos, Eliude R. Nascimento, Amanda Raquel Gomes, Eliude Rodrigues do Nascimento, Mayara FERREIRA Mota, Tayssa CL Vilhena, Williams Fernandes Barra
Journal: Journal of Clinical Oncology (2015)

e12641 Background: Advances in studies on cancer genetics allowed the perception that breast cancer is a complex group of tumors, that beyond similar topography and histologies, are molecular and genetically very different and thus, clinically heterogeneous. Understanding these singularities can provide prognostic information and assist in the discovery of more effective therapies, once the mammary carcinoma is the most common malignancy in women worldwide and its incidence is increasing. In this sense, this project aims to characterize the immunohistochemical profile of breast cancer in women in the Brazilian Amazonia. Methods: A transverse retrospective prevalence study was conducted by reviewing medical records of 316 patients with breast cancer. The included variables were age, menopausal status, disease clinical staging, histological type, profile hormone receptors (estrogen and progesterone), expression of the 2 receptor human epidermal growth factor (HER2) and Ki67 proliferative index, obtained by immunohistochemical method. Results: The immunohistochemical profile analisis showed the following distribution: Luminal A 34.8% (N 110), Luminal B 48.4% (N 153), Her-2 overexpression 4.7% (N 15), Triple negative 12% (N 38). Luminal A type tumors were related to a protective effect of 61% on advanced clinical staging (p = 0,05; OR = 0,61, CI95% = 0,38-0,9), while triple negative tumors increased three times the risk to III or IV clinical stagings (p < 0,01; OR = 3,62; CI95% = 1,75-7,49). It was found a tendency for young women to present triple negative breast cancer (p = 0,08; OR = 0,97; CI95% = 0,95-1,0). Conclusions: The luminal A tumors corresponded to beyond 80% of the sample, wich were correlated to initial clinical stagings. Triple-negative tumors were more prevalent in young women and advanced breast cancer.
Risk of Bias and Heterogeneity—Reply
Authors: Mizuki Nishino, Anita Giobbie-Hurder, F. Stephen Hodi
Journal: JAMA Oncology (2017)

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Prognostic value of serum carbohydrate 19-9 in patients receiving gemcitabine-based neoadjuvant therapy for pancreatic cancer.
Authors: Kabir Mody, Joseph J. Shatzel, Spencer L. James, Rebecca Wang, Thomas Anthony Colacchio, Richard J. Barth, Bassem I. Zaki, Michael J. Tsapakos, Arief A. Suriawinata, John E. Sutton, Stuart R. Gordon, Timothy B. Gardner, Kerrington D. Smith, Gregory H. Ripple, Kathryn Cunningham Hourdequin, Gregory J. Tsongalis, Elizabeth Boutin McGrath, J. Marc Pipas
Journal: Journal of Clinical Oncology (2014)

e15189 Background: The role of neoadjuvant therapy in pancreatic ductal adenocarcinoma (PDAC) remains unclear, but has demonstrated benefit in many studies. CA 19-9 is a commonly used tumor marker in the clinical management of PDAC, but its prognostic role in neoadjuvant therapy is not well defined. The goal of this study was to determine the relationship between CA 19-9 changes after neoadjuvant therapy and subsequent outcomes in patients with non-metastatic PDAC. Methods: We performed a retrospective review of all patients with resectable, borderline resectable, and locally advanced PDAC who received neoadjuvant therapy at our institution between 1996 and 2012. For inclusion, patients needed a serum CA 19-9 >40 U/ml and bilirubin ≤2 mg/dl at the initiation of therapy. We evaluated associations between Ca 19-9 pre- and post- neoadjuvant therapy (NT) and outcome variables including completion of surgery, overall survival, and progression-free survival. Results: Of the 145 patients included, 30 had resectable disease (20%), 56 had borderline resectable disease (39%), and 59 had locally advanced disease (41%). Post-NT CA 19-9 normalized to <40U/ml in 54 patients (37%). Seventy patients (48%) underwent resection. Patients with post-NT CA 19-9 <40U/ml had significantly higher odds of undergoing resection (OR 2.95 p = 0.02). Normalization of post-NT CA19-9 was associated with improved survival (HR=0.58 p=0.006), even after adjusting for successful resection. CA19-9 normalization was predictive of longer OS in patients with borderline disease (HR (0.320, p = 0.001). Completion of resection was also prognostic for overall survival (HR 0.30 p<0.001). Median OS in resected patients who normalized CA 19-9 was 27.3 months, and 20.9 months in those who did not (p = 0.10). Normalization of post-NT CA19-9 in those who did not complete resection was also associated with longer overall survival, with a median OS of 15.1 months, compared to 8.5 months (p=0.032). Conclusions: Normalization of CA 19-9 to <40U/ml with neoadjuvant therapy is highly prognostic for resection and overall survival in patients receiving gemcitabine-based neoadjuvant chemoradiation therapy.
The relationship between tumour response, stabilisation of disease and survival: A meta-analysis of two Phase III studies on topotecan in relapsed ovarian cancer
Authors: S. J. Gwyther, G. A. Ross, G. C. Dane, M. A. Paules, B. Dharan, T. Crofts
Journal: Journal of Clinical Oncology (2004)

9721 Background:Tumour response is the major surrogate by which new cancer therapies are evaluated. However, demonstrating a consistent relationship between response and survival has been problematic, and establishing the clinical benefit associated with prolonged stabilisation of disease has been particularly elusive. Methods:In order to establish a relationship, it must be shown that the measurement of response is objective and repeatable, between studies and between reviewers. In the studies described, the measurement of tumours was consistent and rigorous using WHO criteria, a specific radiology protocol and centralised radiological review which was “blinded” to the therapy received. Retrosepctive analysis (Lane et al) shows that response and stabilisation of disease (SD) by these rigorous criteria are proportional to survival. In order to enable definitive conclusions to be drawn about the relationship between response/SD and survival, two sources of potential bias have been eliminated. Firstly, lead-time bias has been eliminated by “landmark analysis” conducted at every 2nd cycle of therapy . Secondly, any source of bias pertaining to patient selection has been eliminated by an analysis of survival as a function of treatment free interval (independent of response and prognostic factors). Results: “Refractory”: TFI 6 mths or less. “Sensitive”: TFI more than 6 mths Conclusions: The results suggest that the rigorous application of WHO criteria enable tumour response and stabilisation of disease to be regarded as potential predictors or surrogates of survival. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Impact of time to surgery in locally advanced rectal cancer patients.
Authors: Madiha Naseem, Manwah Yeung, Suruthi Senthilvel, Pooya Dibajnia, Doshina Naila, Brendan Singh, Sandra De Montbrun, Marcus J. Burnstein, Nancy N. Baxter, Christine B. Brezden
Journal: Journal of Clinical Oncology (2017)

719 Background: Patients with locally advanced rectal cancer (LARC) undergo surgery at 6-8 weeks after neoadjuvant chemoradiation based on standard protocol. However, the optimal time to undergo surgery remains debatable. The goal of this study was to identify associations between time to surgery and additional variables with overall survival (OS) and recurrence rates in LARC patients. Methods: A retrospective chart review was conducted for 80 LARC patients with T3 or node positive disease, who have undergone neoadjuvant chemoradiation and surgery at St. Michael’s Hospital from January 1st 2005-December 31st 2015. Patients were divided into 4 groups based on time to surgery: 4-6 weeks (group 1), 6-8 weeks (group 2), 8-10 weeks (group 3), and &gt; 10 weeks (group 4). Cox proportional hazards model was used to find associations with recurrence and OS. Results: Of the 80 patients, 67.5% (n = 54) were male and 32.5% (n = 26) were female. Median age at diagnosis was 59 years (range, 28-80 years). Median follow-up was 4.84 years. Recurrence occurred in 29% (n = 23) of patients. Incidence of death was 11% (n = 9). Pathologic complete response (pCR) was achieved in 15% (n = 12) of patients. Statin use during chemoradiation was prevalent in 25% (n = 20) of patients. Compared to group 1, patients in group 2 had a 14% reduction in the risk of recurrence (hazard ratio (HR): 0.86, 95% CI: 0.252.91); group 3 had a 69% reduction (HR: 0.31, 95% CI: 0.081.22) and group 4 had a 55% reduction (HR: 0.45, 95% CI: 0.073.08). There was no statistically significant difference in OS between the 4 groups. Furthermore, patients who took statins during chemoradiation had improved OS (HR: 5.42, 95% CI: 39.27.48, p &lt; 0.019) with no difference in pCR rate. Conclusions: This study shows that surgery at 8-10 weeks after chemoradiation offers the best disease-free survival outcome. It also highlights a mortality benefit conferred by statin use during chemoradiation. This could be attributed to the radiosensitizing effects of statins, which allow tumor stem cells to undergo enhanced autophagy. Further prospective studies are warranted to investigate this therapeutic benefit.
Migration of mitochondrial DNA in the nuclear genome of colorectal adenocarcinoma
Authors: Vinodh Srinivasainagendra, Michael W. Sandel, Bhupendra Singh, Aishwarya Sundaresan, Ved P. Mooga, Prachi Bajpai, Hemant K. Tiwari, Keshav K. Singh
Journal: Genome Medicine (2017)

Colorectal adenocarcinomas are characterized by abnormal mitochondrial DNA (mtDNA) copy number and genomic instability, but a molecular interaction between mitochondrial and nuclear genome remains unknown. Here we report the discovery of increased copies of nuclear mtDNA (NUMT) in colorectal adenocarcinomas, which supports link between mtDNA and genomic instability in the nucleus. We name this phenomenon of nuclear occurrence of mitochondrial component as numtogenesis. We provide a description of NUMT abundance and distribution in tumor versus matched blood-derived normal genomes.Whole-genome sequence data were obtained for colon adenocarcinoma and rectum adenocarcinoma patients participating in The Cancer Genome Atlas, via the Cancer Genomics Hub, using the GeneTorrent file acquisition tool. Data were analyzed to determine NUMT proportion and distribution on a genome-wide scale. A NUMT suppressor gene was identified by comparing numtogenesis in other organisms.Our study reveals that colorectal adenocarcinoma genomes, on average, contains up to 4.2-fold more somatic NUMTs than matched normal genomes. Women colorectal tumors contained more NUMT than men. NUMT abundance in tumor predicted parallel abundance in blood. NUMT abundance positively correlated with GC content and gene density. Increased numtogenesis was observed with higher mortality. We identified YME1L1, a human homolog of yeast YME1 (yeast mitochondrial DNA escape 1) to be frequently mutated in colorectal tumors. YME1L1 was also mutated in tumors derived from other tissues. We show that inactivation of YME1L1 results in increased transfer of mtDNA in the nuclear genome.Our study demonstrates increased somatic transfer of mtDNA in colorectal tumors. Our study also reveals sex-based differences in frequency of NUMT occurrence and that NUMT in blood reflects NUMT in tumors, suggesting NUMT may be used as a biomarker for tumorigenesis. We identify YME1L1 as the first NUMT suppressor gene in human and demonstrate that inactivation of YME1L1 induces migration of mtDNA to the nuclear genome. Our study reveals that numtogenesis plays an important role in the development of cancer.
Potential predictive value of hepatocyte growth factor (HGF) in advanced non-small cell lung cancer (NSCLC) treated with a platinum doublet and bevacizumab.
Authors: Jeffrey Allen Borgia, Ravi Pithadia, Zahraa Ibrahem, Cristina Fhied, Sanjib Basu, Wen-rong Lie, Mary J. Fidler, Marta Batus, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2014)

e22000 Background: Angiogenesis is implicated in disease progression/poor clinical outcome in multiple carcinomas, including lung cancer. Predictive biomarkers for bevacizumab and other anti-angiogenic agents have not been identified to aid in directing Tx decisions for frontline NSCLC patients. We evaluated a panel of serum biomarkers in non-squamous NSCLC patients immediately preceding treatment with chemotherapy with or without bevacizumab, at the discretion of the treating physician. Methods: Pretreatment (pre-Tx) serum from 68 Pts with frontline stage IV NSCLC were evaluated with the Human Angiogenesis Growth Factor Panel (EMD Millipore) containing angiopoietin-2, BMP-9, EGF, endoglin, endothelin-1, FGF-1, FGF-2, follistatin, G-CSF, HB-EGF, HGF, IL-8, leptin, PLGF, VEGF-A, VEGF-C, and VEGF-D on a FlexMAP 3D system (Luminex Corp.). Pts were treated with either standard platinum doublets (CTx; n=42) or CTx with bevacizumab (CTx+bev; n=26) according to physician choice. Disease responses were defined by RECIST criteria. Each analyte was assessed for rapid progression (threshold of 90 days) using Fisher exact test and associated with progression free survival (PFS) and overall survival (OS); results were compared between Tx regimens. Multivariate Cox PH analysis was used to identify interaction of markers with CTX/CTX+bev on PFS and OS. Results: High pre-Tx levels of endothelin-1, follistatin, and VEGF-C were significantly associated (p≤0.05) with a high risk of disease progression within 90 days of Tx initiation - regardless of Tx type. High HGF levels were differentially associated with poor OS (interaction HR=0.44; p=0.03) and PFS (interaction HR=0.56; p=0.012) in Pts receiving CTx+bev, relative to CTX alone. Similarly, high levels of endoglin was differentially associated with an inferior PFS (HR=0.48; p<0.01) in the CTx+bev cohort, relative to those receiving CTx alone. Conclusions: Results from this small series of non-randomized patients suggest that the relevance of serum HGF levels warrants additional study in patients treated with bevacizumab and other anti-angiogenic agents.
Cardiovascular screening in long-term Hodgkin lymphoma survivors.
Authors: Benjamin Reed Griffin, Carrie A. Thompson, Thomas Matthew Habermann, Thomas E. Witzig, Kay Ristow, Joerg Herrmann
Journal: Journal of Clinical Oncology (2014)

e20592 Background: Hodgkin Lymphoma (HL) is highly curable, with an 85% 5-year survival rate. HL survivors have higher mortality rates than their peers, in part due to increased rates of cardiovascular (CV) disease. Therefore, consensus and expert recommendations include aggressive management of CV risk factors and consideration of screening for CV disease, depending on exposure to chemotherapy and radiotherapy. However, the frequency of compliance with these recommendations is not known. Methods: Patients treated for HL at Mayo Clinic Rochester from 1998-2008 were identified. Those who received radiation therapy >25 Gy and/or anthracycline chemotherapy >240 mg/m2 and had follow-up medical records after 2010 were reviewed to determine provider specialty and if CV screening or counseling regarding CV risk factors was documented. P-values were calculated using Chi squared method. Results: 96 patients were identified who were a mean of 9.3 years (range 5-15) from HL diagnosis. 32 (33%) patients had documented counseling about CV risk factors, but “history of HL treatment” was stated as the rationale for counseling in only the minority (16%) of cases. All patients had BP measured, 85 (89%) had glucose testing, and 44 (46%) had lipid testing. 19 (20%) received a CV screening test (most commonly echocardiogram (19%), followed by stress test (4%) and coronary CT (3%)). Among patients seen by a hematologist, 29% (23/79) had documented counseling on CV risks, compared to 53% (9/17) with primary care follow-up alone (p=.059). However, 18% (15/79) seen by a hematologist were counseled specifically referencing HL, compared to 0% (0/17) with primary care follow-up alone (p = .047). Among patients seen by a hematologist, 20% (16/79) received cardiac tests, compared to 18% (3/17) with primary care follow-up alone (p=.80). 11% (9/79) received testing due to their HL history when seen by a hematologist, compared to 0% (0/17) with primary care follow-up alone (p = 0.14). Conclusions: Despite the CV risk related to HL therapy, in this retrospective review few survivors had documented counseling or screening for CV disease. Rates were low among both primary care and hematology physicians. Integrated survivorship care and education of providers should remain a high priority.
Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF–IRF4 transcription factor complex
Authors: Arifumi Iwata, Vivek Durai, Roxane Tussiwand, Carlos G Briseño, Xiaodi Wu, Gary E Grajales-Reyes, Takeshi Egawa, Theresa L Murphy, Kenneth M Murphy
Journal: Nature Immunology (2017)
Electronic prompt to improve outpatient code status documentation for advanced lung cancer.
Authors: Jennifer S. Temel, Joseph A. Greer, Emily R. Gallagher, Vicki A. Jackson, Inga Tolin Lennes, Elyse R. Park, William F. Pirl
Journal: Journal of Clinical Oncology (2012)

6048 Background: Rates of documentation of end-of-life care preferences in the medical record remain low, even among patients with incurable malignancies. The goal of this study was to assess the impact of electronic prompts to encourage oncology clinicians to document code status in the outpatient electronic health record (EHR) of patients with advanced lung cancers. Methods: We conducted two clinician focus groups (n=15) at an affiliated academic medical center to determine the appropriate content and timing of the electronic reminders. Based on the focus groups, we developed email reminders that were timed to the start of each new chemotherapy regimen. Between 6/09 and 1/11, 102 eligible patients with advanced lung cancer were approached, and 100 (98%) agreed to participate in the prospective study. Email reminders were sent to oncology clinicians at the patient's next outpatient visit and with each new chemotherapy regimen. Using a pre-post design, we compared study participants to a retrospective cohort of 100 consecutive historical controls who began chemotherapy for advanced lung cancer at least one year prior to the start of this study. The primary outcome measure was the documentation of code status in the EHR. Results: Study participants were similar to historical controls, with no significant differences in age, gender, performance status, histology or initial cancer therapy received. At one year follow-up, 33/98 (34%) of participants had a code status documented in the outpatient EHR compared with 12/83 (15%) of historical controls, p=0.003. Mean time to code status documentation was significantly shorter in study participants (8.6 months [95% CI 7.6-9.5]) compared with controls (10.5 months [95% CI 9.8-11.3]), p=0.004. Conclusions: Email prompts triggered by changes in chemotherapy improved the rate and timing of code status documentation in the EHR.
Is universal <i>HLA-B*15:02</i> screening a cost-effective option in an ethnically diverse population? A case study of Malaysia
Authors: H.Y. Chong, Z. Mohamed, L.L. Tan, D.B.C. Wu, F.H. Shabaruddin, M. Dahlui, Y.D. Apalasamy, S.R. Snyder, M.S. Williams, J. Hao, L.H. Cavallari, N. Chaiyakunapruk
Journal: British Journal of Dermatology (2017)

A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs.
ONC-2012-001: A single-arm phase II study of tivantinib (ARQ 197) plus cetuximab in EGFR inhibitor-resistant MET high patients (pts) with locally advanced or metastatic colorectal cancer (CRC) with wild-type KRAS.
Authors: Lorenza Rimassa, Silvia Bozzarelli, Alberto Zaniboni, Paolo Foa, Carlo Carnaghi, Rodolfo Passalacqua, Monica Ramello, Luca Di Tommaso, Laura Giordano, Armando Santoro
Journal: Journal of Clinical Oncology (2014)

TPS3661 Background: MET overexpression has been identified in 30-70% colorectal cancer (CRC) and activation of this pathway can be associated to resistance to cetuximab (Krumbach R et al, Eur J Cancer 41:1231-43, 2011). Tivantinib (ARQ 197) is a non-adenosine triphosphate (ATP)-competitive, oral inhibitor of the MET receptor tyrosine kinase. The ARQ 197-A-U252 phase I/II trial in wild-type KRAS metastatic CRC (mCRC) demonstrated that tivantinib in combination with irinotecan and cetuximab is well tolerated and showed encouraging antitumor activity, particularly in MET-high patients (pts) (Eng C et al, J Clin Oncol 31, 2013; suppl, abstr 3508). Additionally in the last years, the potential role of epidermal growth factor receptor inhibitors beyond progression in mCRC has been evaluated. Adding tivantinib to cetuximab is based on a strong rationale to improve outcome in cetuximab resistant MET-high mCRC pts. Methods: Enrollment in this single-arm, Simon 2-stage, phase II study (ONC-2012-001) has begun. Eligible pts have: MET-high (at immunohistochemistry), surgically unresectable, locally advanced or metastatic CRC; received >1 prior systemic therapy for advanced or metastatic disease; progressed on or after a cetuximab or panitumumab containing regimen after a best response of at least stable disease and within three months before enrollment; Eastern Cooperative Oncology Group performance score < 2; adequate bone marrow, liver and kidney functions. Pts receive tivantinib 240 mg p.o. twice daily plus cetuximab 500 mg i.v. every two weeks and are evaluated by CT or MRI scan at eight-week intervals. The primary endpoint is objective response rate. Secondary endpoints include progression-free survival, overall survival and safety. Treatment continues until disease progression or unacceptable toxicity. Pts discontinued from study treatment will be followed for survival. As of January 28, 2014, four of the planned first-stage 21 pts have been enrolled. This trial is expected to complete enrollment by the end of 2014. Clinical trial information: NCT01892527.