tbuckley/cabot-search huggingface dataset:
Effect of cytidine deaminase (CDA)–related biomarkers on overall survival in patients with advanced pancreatic cancer receiving gemcitabine (GEM) monotherapy.
Authors: H. Ueno, N. Kaniwa, E. Sugiyama, J. Furuse, H. Ishii, Y. Satoh, T. Yoshida, N. Saijo, Y. Saito, T. Okusaka
Journal: Journal of Clinical Oncology (2011)

e14645 Background: CDA metabolizes GEM to an inactive metabolite, 2’,2’-difluorodeoxyuridine (dFdU). We have already reported the impact of CDA-related biomarkers on GEM-induced toxicities (Sugiyama, J Clin Oncol. 2007; and Ueno, Br J Cancer. 2009). This study was intended to clarify the effects of CDA-related phenotypic and genetic biomarkers on the overall survival of advanced pancreatic cancer pts treated with GEM monotherapy. Methods: Using advanced pancreatic cancer (stage IV) pts enrolled in the first study (n=73) and the second study (n=98) who received a 30-minute intravenous GEM infusion at a dose of 1,000 mg/m2, the overall survival was analyzed for associations with the pharmacokinetic parameters of GEM and dFdU, plasma CDA activity and nonsynonymous SNPs of CDA {79A>C (CDA*2) and 208G>A (CDA*3) } as well as the pts’ background factors. Results: In the first study, overall survival was significantly longer in pts with longer mean residence time (MRT) of GEM and lower plasma concentration of dFdU at 0.5hr (C0.5) than in pts with a shorter GEM MRT and higher dFdU C0.5 (p=0.0138 and p=0.0011, respectively). Low plasma CDA activity and heterozygous CDA*3 were also significantly associated with prolonged overall survival (p=0.0062 and p=0.0247, respectively). After adjusting with the pts’ background factors, CDA related biomarkers were still significantly associated with overall survival in the multivariate Cox proportional hazard models. Association of low plasma CDA activity with prolonged overall survival was also confirmed by the second study (p=0.0061). Conclusions: In GEM monotherapy, reduced CDA activity correlated well with prolonged survival of advanced pancreatic cancer pts. CDA*3 is one of the factors that reduced the CDA activity in Japanese pts. 1st study 2nd study No. of pts MST P value No. of pts MST P value Plasma CDA activity High 18 5.3 mo 0.0062 42 5.1 mo 0.0061 Low 16 8.1 mo 37 8.6 mo CDA*2 Negative 44 6.1 mo 0.2546 56 7.1 mo 0.3819 Positive 26 4.5 mo 30 7.2 mo CDA*3 Negative 65 5.4 mo 0.0247 81 6.9 mo 0.1771 Positive 5 17.3 mo 5 11.7 mo
The patients’ perspective on maintanance therapy (MT): Results of a survey applying a semistructured interview.
Authors: S. Frank, I. Meisinger, G. Marckmann, H. Kopp, L. Kanz, M. Wickert, F. Mayer
Journal: Journal of Clinical Oncology (2011)

e19653 Background: Palliative chemotherapy is frequently applied for a limited number of cycles. Afterwards, the patients (pts) are followed without treatment until a second line therapy is initiated due to progression. MT is considered a treatment option instead of therapy-free follow up. MT is approved in low grade non Hogdkin’s lymphoma, colorectal cancer and lung cancer (LC). Pts undergoing MT trade a period undisturbed by any anti-tumor treatment for a limited gain in overall survival (OS). We assessed – in a hypothetical setting - pts’ preference regarding treatment with MT versus follow-up, the side effects pts were willing to tolerate and the gain in survival that would justify MT for the indivual pt. Methods: pts suffering from lymphoma, LC or gastrointestinal cancer (GIC) were surveyed by a semi-structured interview during their 4th or a subsequent cycle of chemotherapy. The survey was purely hypothetical, individual MT was not discussed within this context. The pts’ preferred route of therapy application and their willingness to tolerate side effects were assessed. In addition, patients were asked which prolongation of life they would require to accept MT. Results: 102 pts with a median age of 64 years were included. Pts suffered from lymphomas (n=33), GIC (n=30), or LC (n=39). 91 pts (89%) would be willing to accept a MT in general. Under the assumption of intense side effects, this value dropped to 47 pts (46%). 23% preferred the oral route, 40% i.v. application, the remaining had no preference. A weekly, three-weekly, or three-monthly schedule would be preferred by 22%, 44%, and 34%. Without side effects, 17% would accept MT assuming a prolongation of OS of at least 3 months, 34% in case of 1 year and 50% in case of 2 years. Conclusions: The majority of pts are willing to accept MT with mild or absent side effects, without a clear preference for the oral route of application. Of note, the majority of pts has unrealistic expectations when it comes to prolongation of OS. We conclude that discussions about MT vs. a stop-and-go approach should include open and precise information on expected prognostic benefits and adverse effects in order to allow the patient to make an informed decision.
Evaluation of an interactive electronic patient-reported outcome (e-PRO) system in outpatient with oral chemotherapy.
Authors: Marika Anna Rasschaert, Konstantinos Papadimitriou, Marc Peeters, Jan Van den Brande
Journal: Journal of Clinical Oncology (2016)

696 Background: Health Information Technology (HIT) is increasingly integrated in clinical cancer care. Simultaneously routine assessment of patient reported outcomes (PROs) has been shown to reliably improve symptom management, identification of psychosocial problems and patient-provider communication. Methods: This study is a single center experience of a multicenter randomized study for the development and validation of an interactive e-PRO tool (RemeCoach). After obtaining informed consent, outpatients, using oral anti-cancer treatment, recorded their medication intake and 17 clinical parameters using this E-PRO tool. The device allowed real time data collection and communication with other care providers via a central platform. The registered data were processed by an algorithm, this algorithm stratifies the data into different grades according to international standards of care (CTCAE v4.0) and clinical importance. Patient clinical and demographic information is collected from medical records and analyzed using descriptive statistics. Results: 21 Patients were included, 62% male, mean age 59,2 (range 38-79). 38% Of patients used capecitabine, 52% regorafenib, 5% pazopanib and 5% sunitinib. Most common symptoms cited were fatigue (95%), myalgia and joint pain (75%) and cough (62%). Median pain score : 3 (Brief Pain Inventory(BPI)). Treatment compliance using the e-PRO was 75%. Conclusions: This study confirms the feasibility of the program, in an outpatient setting. This e-tool provides a means to register compliance, early symptoms of disease and toxicity of treatment.The compliance to the e-PRO tool will be confirmed, with further development of this program in a multicenter, randomized design. Evaluation of quality of life PRO-measurements and further exploration of the relationship between optimal pharmacovigilance and improvement of patient’s outcome will ensue.
Identification of the gastric microbiome from endoscopic biopsy samples using whole genome sequencing.
Authors: Chao Zhang, Kyle Cleveland, Felice Schnoll-Sussman, Bridget McClure, Michelle Bigg, Prashant Thakkar, Nikolaus Schultz, Eric G. Pamer, Doron Betel, Manish A. Shah
Journal: Journal of Clinical Oncology (2015)

8 Background: H. pylori is the primary risk factor for gastric cancer (GC). However, virtually all infected patients do not develop GC, and H. pylori eradication does not reduce GC risk. We established a whole genome sequencing (WGS) pipeline to detect the gastric microbiome from small endoscopic samples directly. With it, we are not only be able to accurately detect H. pylori infection in GC, but also examine the microbiome in samples from other malignancies. Methods: Patients (pts) undergoing upper endoscopy without chronic inflammatory disease or chronic NSAID use were eligible for participation, categorized as follows: (1) active infection (H. pylori identified on biopsy, or positive CLOtest), (2) prior infection (previous H. pylori treatment, or ELISA IgG positive), and (3) gastric cancer. Endoscopic biopsies from 3 locations in the antrum/body were freshly frozen for WGS on a HiSeq2500 platform at ~10X coverage. Our customized computational pipeline successively removes human sequences, with remaining un-mapped reads aligned to 1,400 unique bacteria genomes. Results: 16 biopsy samples taken from 10 pts were sequenced. All H. pylori positive samples detected by our pipeline have been successfully validated by qPCR. Surprisingly, H. pylori was identified in previously treated pts. We also applied our pipeline to control samples to evaluate the performance of bacterial identification. Negative sample are blood samples from HapMap projects with human DNA only. In contrast, positive samples are bacteria enriched samples from Human Microbiome Project. Our identifications matched the previously reported results. Finally, we profiled 37 gastric cancer tumors and matching normal WGS samples from TCGA and found that 40% of them are H. pylori positive. This result is a novel discovery that was not reported in the TCGA GC study. Conclusions: This is the first demonstration of detailed unbiased microbiome detection performed from gastric endoscopic biopsy samples using WGS. We found that standard treatment does not always eradicate H. pylori possibly explaining why H. pylori treatment fails to reduce cancer risk. We also found that ~40% of gastric cancers have evidence of persistent H. pylori bacterial content.
Maintenance programme could help people keep weight off, research finds
Authors: Jacqui Wise
Journal: BMJ (2017)

People tend to regain 1-2 kg a year after successfully losing weight, but new research published in the Annals of Internal Medicine shows that incorporating a maintenance intervention into clinical or commercial weight loss programmes could help prevent or slow down this weight gain.1

The randomised trial included 222 obese patients (body mass index …
Presenting features of colorectal cancerin the Sulaimaniya province of Iraqi Kurdistan.
Authors: S. Y. Sheet, A. K. Sheikha, A. M. Saaed, H. A. M. Ameen, S. S. Mohammed, M. Khasraw
Journal: Journal of Clinical Oncology (2011)

e14148 Background: Colorectal cancer is the third commonest cancer in both developed and developing world. Early detection of colorectal cancer is essential for successful management. Little is known about the patterns of presentations and characteristics of colon cancer in Iraq in general and specifically in Kurdistan. Methods: After appropriate institutional approvals were obtained, a retrospective review of 100 consecutive patients from Hiwa Hospital with histopathologically proven colorectal cancer were analyzed for baseline characteristics, clinical presentation, pathological tumor subtype and stage at diagnosis. Subsequently, each patient was interviewed in person or by telephone to complete any the missing data. The results were compared to international figures from elsewhere. Results: All required data were obtained. The median age was 52 years (range 20-90). There were 54 men and 46 women. One third of patients (n=29) were younger than 40 years. Ten patients (10%) presented with early colon cancer and 90 patient (90%) presented with more advanced disease (stage III and IV). Sites of disease were right colon (n=18; 18%), left colon (n=45; 45%), rectum (n=37; 37%). Eighty-two patients (82%) had left colonic and rectal tumors; 37 (37%) had rectal cancer, and 45 (45%) had left colonic cancer. Conclusions: One third of colorectal cancer patients are in young patients, which is much higher than comparable international figures in this age group (< 40 years). Tumors were more often located in the distal colon and rectum. This highlights the need for future research to explore potential explanations. Most patients are diagnosed late, mostly with stage III and IV.
Extranodal NK/T-Cell Lymphoma: A Comparative Clinicopathological Study According to Survival Outcome.
Authors: Yong Won Choi, Jung Il Park, Jae Ho Jung, Sung Heun Jeong, Hyun Woo Lee, Jae Ho Han, Seon Yong Jeong, Seok Yun Kang, Joon Seong Park, Jin Hyuk Choi, Hugh C. Kim
Journal: Blood (2007)
MicroRNA analysis of fine-needle aspirates from pancreatic cancer.
Authors: Philip Agop Philip, Husain Saleh, Shadan Ali, Wei Chen, Paulette Palazzolo, Seema Sethi, Fazlul H. Sarkar
Journal: Journal of Clinical Oncology (2012)

200 Background: Tissue-based research is a major challenge in localized pancreatic cancer (PC) especially those with locally advanced unresectable or borderline resectable disease. Approximately half of the patients are diagnosed by a fine needle aspirate (FNA) /biopsy of the pancreatic primary tumor with limited tissue available for correlative assays. Micro-RNAs (miRNAs) are biomarkers with the potential to be developed for prognostic and predictive purposes. Moreover, these molecules can facilitate the development of targeted therapies in PC. Methods: miRNA expression profiling and quantitative real-time PCR (qRT-PCR) were performed from RNA (25-100 ng per patient) extracted from formalin-embedded cell blocks (FFPE) obtained from diagnostic FNA of the pancreas. Expression profiles of miRNAs were compared to those from patients undergoing pancreatic biopsy for non-malignant conditions. Results: Cell blocks from FNAs from twenty-nine and 15 patients with pancreatic adenocarcinoma and non-malignant conditions were studied, respectively. miRNA profiling demonstrated deregulation of over 228 miRNA. The top 7 were validated by qRT-PCR. The expression of let-7c, let-7f, and miR-200c were significantly reduced in most patients. Conversely, the expression levels of miR-486-5p and miR-451 were significantly elevated. Significant interindividual variations were also noted in expression of certain miRNAs. Conclusions: FFPE obtained from diagnostic FNA of pancreatic tumor can be a valuable resource to study miRNA expression profiles of multiple miRNAs and undertake qRT-PCR in patients with localized PC and further supports the use of diagnostic FNA in RNA-based translational research. miRNA expression can be developed for use as prognostic and predictive biomarkers in future clinical trials in patients with PC.
Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for stage III colon cancer patients who underwent curative resection (KSCC1303).
Authors: Nobutomo Miyanari, Yasunori Emi, Akihito Tsuji, Kenji Sakai, Hideaki Anai, Hiroaki Takeshita, Hiroshi Imamura, Shinichiro Mori, Takayuki Shimose, Eiji Oki, Hiroshi Saeki, Yoshihiro Kakeji, Yoshito Akagi, Hideo Baba, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2016)

739 Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.
Quality of bone marrow biopsy as compared to the 2008 WHO guidelines.
Authors: A. M. Padurean
Journal: Journal of Clinical Oncology (2010)

e17005 Background: There is an abundance of articles dealing with new cellular markers, subcellular pathways or sophisticated DNA analysis; nevertheless, morphology continues to be the main criterion for diagnosing hematological malignancies. Also, the accuracy of morphological evaluation and even special testing (flow cytometry, cytogenetics, etc.) depends significantly on the quality of specimen collected. The 2008 WHO blue book stippulates, for the first time, that the bone marrow core biopsy should be at least 1.5 cm in length. Methods: From April 2005 to December 2009, 1,041 consecutive bone marrow biopsies and aspirates were recorded. 760 specimens were obtained by oncologists, 247 by pathologists and 34 by others. The bone marrow aspirates only and the biopsies obtained by personnel other than oncologists or pathologists were excluded. 966 cores were measured grossly and their length adjusted at microscopic examination by subtracting the portion involved by artifacts (aspiration, crush, etc). Results: The cores obtained by oncologists measured an average length of 1.56 cm and the cores obtained by pathologists 1.77 cm. 347 cores (48%) obtained by oncologists and 76 (31%) obtained by pathologists were less than 1.5 cm in length. The “readable” length (core without artifacts) was further decreased at microscopic examination to 1.17 cm for oncologists and 1.59 cm for pathologists, thus increasing the number of cores less than 1.5 cm in length to 475 (66%) for oncologists and 98 (40%) for pathologists. Conclusions: Based on the data presented, both oncologists and pathologists need to obtain longer cores and avoid introducing artifacts that affect the readable portion of the biopsy. Also, the pathologists seem to fare better than the oncologists at obtaining more adequate biopsies. The 2008 WHO guidelines recommend a bone marrow core biopsy of at least 1.5 cm in length. This is much necessary but not sufficient a condition for an accurate morphological evaluation. Additional guidelines for obtaining optimal bone marrow aspirations would be welcome. No significant financial relationships to disclose.
The prognostic role of the epidermal growth factor receptor (EGFR) in patients with metastatic gastric cancer receiving first-line chemotherapy: Results from the FLO versus FLP gastric cancer phase III trial of the AIO
Authors: C. Pauligk, R. M. Wirtz, K. Steinmetz, S. Probst, J. T. Hartmann, R. Hofheinz, N. Homann, H. M. Altmannsberger, C. Petry, E. Jäger, S. Al-Batran
Journal: Journal of Clinical Oncology (2008)

22033 Background: This study was conducted to assess the prognostic role of EGFR in metastatic gastric cancer (MGC), with a view towards the future introduction of anti-EGFR therapy for MGC. Methods: Tumor samples from pts who received first-line 5- fluorouracil, leucovorin and platinum for MGC within a phase III trial of the AIO were prospectively analyzed. The expression of EGFR was assessed by immunohistochemistry (IHC) and by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, pAKT, pMAPK, HER2/neu, Ki-67, T-cells and VEGF-A were evaluated (by qRT-PCR and/or immunohistochemistry). Results: 288 samples from 168 out of 220 patients (pts) enrolled were analysed. EGFR was expressed in 47% of pts (1+, 24%; 2+, 39%; 3+, 37%). The expression was highest in intestinal type histology (48%) and surgically resected tissues (50%) and lowest in diffuse type histology (29%) and biopsy tissues (34%). There was no difference in EGFR expression between primary tumors and metastases (40%, each). HER2/neu over-expression (3+) was detected in 20.7% of pts. EGFR expression (any grade) correlated with prolonged median overall survival (10.8 months in EGFR+ and 8.2 months in EGFR- pts; log rank p=.026), but not with Response rate (RR) or progression-free survival. This correlation was maintained in the multivariate analysis (p=.028) and was independent from age, sex, ECOG, type of histology, treatment, liver and peritoneal involvement. Interestingly, within the group of EGFR+ tumors, the intensity of EGFR expression correlated inversely with response to chemotherapy and survival (RR: 53% v 32% v 19% in EGFR 1+ v 2+ v 3+ tumors, respectively; 2-sided p=.032). EGFR protein expression did not correlate with EGFR mRNA. Further correlative results (e.g. VEGF/pMAPK) will be presented. Conclusions: The pattern of the prognostic impact of EGFR in MGC was complex. EGFR expression (any grade) was a positive prognostic factor. However, once EGFR is expressed, over-expression represented a negative predictive factor. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Siemens Medical Solutions
Evaluation of a cancer gene sequencing panel in a hereditary risk assessment clinic.
Authors: Allison W. Kurian, Emily E. Hare, Meredith Mills, Lisa McPherson, Kerry Kingham, Alice S. Whittemore, Valerie McGuire, Gail Gong, Uri Ladabaum, Michele Cargill, James M. Ford
Journal: Journal of Clinical Oncology (2013)

7 Background: Multiple-gene sequencing panels are entering clinical practice. We report on research testing with a custom sequencing panel comprising 43 genes and 32 cancer-associated variants among patients referred for assessment of hereditary breast and ovarian cancer risk. Methods: Patients referred to the Stanford Cancer Genetics Program for clinical BRCA1 and BRCA2 (BRCA1/2) mutation testing from 2002-2012 were invited to donate a blood sample for research on an Institutional Review Board-approved protocol. Blood samples were frozen at -80 degrees, and DNA extracted after &lt;1-10 years. The entire coding region, exon-intron boundaries (+/- 10bp) and all known pathogenic variants in other regions were sequenced for 43 genes that have published associations with risk of breast, ovarian and other cancers. An additional 32 cancer-associated variants were also sequenced. Clinically significant results were disclosed to patients. Results: Germline DNA samples were sequenced from 199 women: 141 had breast cancer, and 57 carried known BRCA1/2 mutations. Analytic results for BRCA1/2 sequencing and pathogenicity interpretations were concordant with prior clinical testing for all patients. Twenty variants designated as pathogenic, either based on published literature or due to a novel truncating or splice donor/acceptor effect, were observed in genes other than BRCA1/2, including ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4. Thirteen patients had pathogenic variants warranting a change in cancer screening or risk reduction based on practice guidelines; they were invited for confirmatory clinical testing and counseling. One 53-year old patient with a personal history of breast and endometrial cancers was found to carry a pathogenic MLH1 mutation; she underwent risk-reducing salpingo-oophorectomy and colonoscopy, with removal of a tubular adenoma. Conclusions: Among patients referred for BRCA1/2 mutation testing, a comprehensive sequencing assay identified 20 [10.1%, 95% confidence interval (CI) 6.5%-15.1%] pathogenic mutations in other genes, of which 13 (6.5%, CI 3.8%-11%) prompted a change in care. Disclosure of research results to participants was feasible and well-tolerated.