tbuckley/cabot-search huggingface dataset:
A western validation of a novel gastric cancer prognostic model using American data.
Authors: Bryan S. Goldner, Ki Jun Song, Taeil Son, Hyoung-Il Kim, Laleh Melstrom, Gagandeep Singh, Sung Hoon Noh, Yuman Fong, Yanghee Woo, Woo Jin Hyung
Journal: Journal of Clinical Oncology (2016)

2 Background: A novel prediction model, the Yonsei University Gastric Cancer Prediction Tool was developed by an international collaborative group (G6+) for accurate determination of 5-year overall survival of gastric cancer patients. This prediction model was created using a prospectively maintained single institution database of 12,399 patients and included clinically relevant factors not accounted for in the TNM staging system. This prediction model was validated using external data sets from Asia; its’ applicability in the American population has yet to be determined through a validated data set. Methods: Using the SEER dataset, 2014 release, all patients with gastric adenocarcinoma diagnosed between the years 2002 –2012 who underwent resection were selected. The following characteristics were selected for analysis: age, sex, gender, depth of tumor invasion, number of positive lymph nodes, total lymph nodes retrieved, presence of distant metastasis, extent of resection, and histology. These data were processed through a recently published prognostic nomogram to obtain concordance index (C-statistic) using the bootstrap method and calibration was assessed. This was compared to the current prognostic index, the TNM staging system. Results: A total of 26,019 possible patients were identified from the SEER database, years 2002-2012. Of these, 11,765 had complete datasets. Validation of the prognostication model revealed a C-statistic of 0.762 (95% CI 0.754-0.769). This is compared to the 7 th TNM staging model, C-statistic 0.683 (95% CI 0.677-0.689). The new nomogram was found to be significantly more accurate with a p-value of &lt; 0.001. Conclusions: Our study validates a novel prediction model for gastric cancer in the American patient population. Using this model, superior accuracy in prognosticating the 5-year survival of gastric cancer patients was confirmed in the western cohort strongly supporting its global applicability. This model also allows for inclusion of those who did not undergo adequate lymphadenectomy or who underwent a non-curative resection and can be a useful prediction tool for an increasing number of gastric cancer patients world-wide.
How often does the patient repeat screening colonoscopy? A study for personalized recommendation of screening colonoscopy interval.
Authors: Eun Sun Kim, Hoon Jai Chun, Yoon Tae Jeen, Bora Keum, Hyuk Soon Choi
Journal: Journal of Clinical Oncology (2016)

527 Background: Colorectal cancer (CRC) is the third most common cancer and the second most frequent cause of cancer death of female and fourth most of male in South Korea. Most CRCs develop through the adenoma–carcinoma sequence, which allows for screening and prevention of CRCs by screening colonoscopic examination and polypectomy. However, there have been limited data on personalized optimal time interval of next surveillance colonoscopic examination. The aim of our study is to recommend personalized interval by analysis of various clinical factors obtained by health care examination. Methods: We enrolled the patients who underwent two times more voluntary, complete screening colonoscopy at health care unit of Korea University Medical Center Anam Hospital from July 1, 2004 to July 31, 2010. The clustering analysis using the partitioning around medoids algorithm and Hierarchial cluster were conducted including the 32 clinical, geographic and laboratory data. For each cluster, we then performed survival analysis that provides the probability of having polyps according to the number of days until next colonoscopy. Results: Totally 8,332 patients underwent screening colonoscopy, among them 625 patients performed repeat colonoscopy exam. 625 patients divided four clusters by clustering analysis. Adenoma detection at first screening colonoscopy was the most potent risk factor of develop of adenoma at next screening. Male gender, triglyceride (&gt;134 mg/dL), and age (&gt;56 years old) were significant factor for decision of the personalized interval of next screening colonoscopy. For example, male patient, who had adenoma at fist screening, the predicted risk of adenoma is 50% after 25 months. Conclusions: Our study can provide personalized time interval of next screening colonoscopy according to patients’ individual clinical data. Further study are necessary for validation our results.
Time to disease-related pain after sipuleucel-T in asymptomatic patients with metastatic castrate-resistant prostate cancer (mCRPC): Results from three randomized phase III trials.
Authors: E. J. Small, C. S. Higano, P. W. Kantoff, J. B. Whitmore, M. W. Frohlich, D. P. Petrylak
Journal: Journal of Clinical Oncology (2011)

4661 Background: Sipuleucel-T, an FDA-approved therapy for men with asymptomatic or minimally symptomatic mCRPC, has a demonstrated survival benefit. In addition to survival data, 3 randomized trials also collected data on time to disease-related pain (TDRP). Methods: D9901 and D9902A enrolled only asymptomatic pts; TDRP was a secondary endpoint. Pain status was collected until disease-related pain or 4 weeks following disease progression, whichever came first. IMPACT originally enrolled only asymptomatic pts with a co-primary endpoint of TDRP; it was later amended to include minimally symptomatic pts and to remove the TDRP endpoint. Pain status for pts enrolled prior to the amendment was collected until disease-related pain was observed. TDRP was assessed in all studies by pain logs and adjudicated by blinded independent reviewers. TDRP was analyzed using the Kaplan-Meier (KM) method and log rank test; HR was derived from an unadjusted Cox regression model. Analyses were based on all randomized pts on D9901 (n=127) and D9902A (n=98), and on IMPACT pts randomized prior to the amendment (n=203). Results: TDRP results were: D9901 HR=0.68, D9902A HR=1.39, and IMPACT HR=0.80. Integrated results were HR=0.84 ([95% CI: 0.64, 1.12]; P=0.24). Separation in the KM curves was seen at approximately 6 months. Median TDRP was 5.6 vs 5.3 months. At 12 months 39.3% of sipuleucel-T vs 18.9% of control pts were estimated to be pain-free. Significant independent baseline predictors of earlier TDRP were higher PSA, higher alkaline phosphatase, lower age, bisphosphonate use, and prior radiation therapy. When adjusted for these clinical factors, the adjusted treatment HR=0.80 ([95% CI: 0.60, 1.08]; P=0.14). Conclusions: The trend towards a delay in TDRP beginning 6 months after randomization is consistent with the potentially delayed anti-tumor effect of immunotherapy. These data provide support for a potential effect of sipuleucel-T on a clinically relevant endpoint proximal to the demonstrated benefit in overall survival. Lack of statistical significance could be due to limited sample size, high rate of censoring, or delayed treatment effect.
Searching for circulating microRNAs in genitourinary tumors.
Authors: Vanessa Medina Villaamil, Guadalupe Aparicio Gallego, Francisco Gomez Veiga, Manuel Valladares Ayerbes, Maria Quindós Varela, Natalia Fernandez Nunez, Aurea Molina Diaz, Isabel Santamarina Cainzos, Luis Miguel Anton Aparicio
Journal: Journal of Clinical Oncology (2014)

468 Background: Detection of circulating tumor cells (CTC) may provide diagnostic and prognostic information in genitourinary tumors (GT). The aim of this work was identify aberrantly expressed miRNAs potentially useful for CTC detection in blood samples from patients with GT to assess their potential clinical significance, and to gain a greater understanding of the mechanisms driving tumor progression. Methods: We examined blood levels of 92 microRNAs in 113 metastatic patients: prostate (mP), renal cell carcinoma (mRCC), bladder tumors (mB) and healthy volunteers (HV) (N=18) using SYBR-green-based microRNA RT-qPCR arrays (Exiqon). Array design was made by literature review and bioinformatics approach using free databases. Relative Expression Software Tool (REST) and SPPS 21.0 were used to data processing and analysis. Results: microRNAs differential expressed between tumors and HV (only up-regulated miRNAs are shown in Table). Conclusions: microRNAs in the circulation are relatively stable, very accessible, low invasive and easily testable biomarkers. These results suggest that our bioinformatic approach is an useful high-throughput method to identified tumors-associated miRNAs. The selected miRNAs should be further evaluated for their potential as markers for CTC detection, prognosis and therapeutic outcome. Further studies of precision and sensitivity on these markers in this GT population will clarify its role as novel stable blood-based markers. [Table: see text]
Effect of weight history on ability to lose weight after a 6-month randomized controlled weight loss trial in overweight breast cancer survivors: The Lifestyle, Exercise and Nutrition (LEAN) study.
Authors: Tara Beth Sanft, Maura Harrigan, Brenda Cartmel, Mary Playdon, Yang Zhou, Erikka Loftfield, Melinda L Irwin
Journal: Journal of Clinical Oncology (2016)

174 Background: Because obesity portends a higher risk of breast cancer mortality, achieving a healthy weight is recommended for breast cancer survivors. The impact of weight history on the ability to lose weight is unclear. We previously reported a 6.2 + 0.7% vs. 2.1 + 0.9% weight loss (p = .0003) in 100 breast cancer survivors randomized to a 6-month weight loss intervention vs. usual care. We examined whether weight history modified the effect of the intervention on body weight changes. Methods: Breast cancer survivors with a BMI &gt; 25 kg/m 2 were randomized to usual care or 6-month, 11-session diet and exercise-counseling intervention. Baseline and 6 month weight and height were measured; weight at ages 18 and 35, 5 years and 1 year before and at diagnosis were self-reported. We defined weight history as: 1) change in weight between each time point and baseline; and 2) duration of obesity (i.e., number of years of having a BMI &gt; 30 between age 18 and baseline). Generalized linear models were used to evaluate mean changes at 6 months between the intervention and usual care groups, adjusted and stratified by weight history variables. Results: Mean age and time since diagnosis were 59 + 7 years and 2.9 + 2.1 years, respectively. BMI increased over time (age 18 BMI = 21.8 + 2.9; baseline BMI = 32.4 + 6.5). Number of years being obese was 5.3 + 8.2 years (range 0-40 years). BMI at baseline, change in BMI from various time points to baseline, and years of obesity did not modify weight loss results. After adjusting for weight history, women randomized to intervention vs. usual care lost 6.1 + 0.7% vs. 2.0 + 0.9%, p = .0006, respectively. Conclusions: Participants reported a history of steady weight gain over time. The duration of obesity did not modify weight loss results. Weight history did not hinder survivors’ ability to lose clinically meaningful weight via a structured intervention.
Phase I trial of radiotherapy with concurrent bevacizumab, erlotinib, and capecitabine for locally advanced pancreatic cancer (LAPC).
Authors: Heath Devin Skinner, Milind M. Javle, Robert A. Wolff, Marilyn V. Clemons, Mark F. Munsell, Marc E. Delclos, Jason B Fleming, Prajnan Das, Christopher H. Crane, Sunil Krishnan
Journal: Journal of Clinical Oncology (2012)

254 Background: The addition of bevacizumab to capecitabine-based chemoradiotherapy (CRT) for LAPC has been shown to be safe. The aim of this study was to determine the safety, tolerability and maximum tolerated dose (MTD) of the addition of erlotinib to this treatment regimen. Methods: Seventeen patients with CT-staged biopsy-proven non-metastatic unresectable LAPC were enrolled between March 2008 and October 2010. Prior chemotherapy was permitted. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose was escalated using a continual reassessment method. Two patients each were enrolled at dose levels (DLs) 1-4 and 9 patients at DL 5. Bevacizumab was escalated from 5mg/Kg every two weeks (DLs 1-4) to 10mg/Kg (DL 5); erlotinib from 100 mg/day (DLs 1-2) to 150 mg/day (DLs 3-5); and capecitabine from 400mg/m 2 twice daily on days of radiation (DL 1) to 600mg/m 2 (DLs 2-3) to 825 mg/m 2 (DLs 4-5). Reassessment for potential resection was performed 6-8 weeks later. Results: With a median follow-up of 10 months (range 3-23), no grade 3 toxicities were observed in DLs 1-4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrheas and 1 rash). No grade 4 or 5 toxicities were seen. DL 4, with a posterior probability of 0.122 of dose limiting toxicity, was selected as the MTD. Median survival was 19.4 months and time to distant progression was 9.8 months. Patients treated at DLs 4 and 5 had a median survival of 24 months. Of 5 patients who underwent margin-negative resections, 4 were originally deemed unresectable and 1 was borderline; 4 were treated at DLs 4 or 5 (36% of patients treated at these DLs); 3 patients had excellent pathological responses (complete response, 5% viable tumor, and 20% viable tumor) at pancreatectomy and are alive at 13, 21 and 22 months respectively with no local or distant failures. Conclusions: The combination of erlotinib, bevacizumab and capecitabine with radiotherapy for LAPC is safe and tolerable. Both the promising survival and the high rate of resectability at the higher dose levels suggest that this strategy of dual inhibition of growth factor receptor pathways during CRT warrants continued evaluation.
Characterization of <i>KRAS, NRAS,</i> and <i>BRAF</i> testing and timing among mCRC patients treated at community cancer centers in the United States.
Authors: Kimberly Lowe, Michael Anthony Kelsh, Kevin McCarl, Gerry C. Bohac
Journal: Journal of Clinical Oncology (2016)

e15086 Background: The requirement to establish RAS status prior to administration of an EGFR inhibitor has increased the need to understand which patients are tested for RAS and the length of time it takes for the treating oncologist to receive the RAS test result. Our objective was to evaluate factors that may influence RAS testing among metastatic colorectal cancer (mCRC) patients and the turn-around time for RAS testing among patients who are treated at community cancer centers in the United States (U.S.) Methods: The sample includes 1550 patients in the Oncology Services Comprehensive Electronic Records (OSCER) database who were diagnosed with mCRC between 1/1/2011 and 8/31/2015. Patient demographics and clinical characteristics were evaluated at the time of mCRC diagnosis. The median number of days and interquartile range (IQR) between the following dates was summarized: diagnosis for mCRC, tissue collection for biomarker testing, tissue was received by the lab for biomarker testing, and biomarker results returned to the oncologist. Results: The frequency of RAS testing was as follows: KRAS (n = 964; 62%), NRAS (n = 116; 7%), BRAF (n = 231; 15%), all three simultaneously (n = 94, 6%). There were significant differences in KRAS testing by age and type of insurance, with young (p < 0.001) and commercially-insured (p = 0.01) patients more likely to receive testing. The median number of days and IQR between specimen collection and diagnosis of mCRC was as follows: KRAS (0; 0 to 443), NRAS (0; -18.5 to 362), and BRAF (-3; -474 to 0). The median number of calendar days between the date the specimen was collected and the date it was received by the lab was as follows: KRAS (19; 1 to 303), NRAS (34.5, 8 to 518), and BRAF (29; 2 to 428). The median number of days between the date the specimen was received by the lab and the date the result was returned to the oncologist was as follows: KRAS (7; 5 to 13), NRAS (10; 7 to 15), and BRAF (8; 6 to 14). Conclusions: Many patients had a specimen collected for biomarker testing at the time of mCRC diagnosis and the results were generally returned to the treating oncologist within one week of it arriving at the lab.
Four questions: Daily assessment of pain, anxiety, problems or concerns, and need to see physician during a course of radiation therapy.
Authors: David D. Howell
Journal: Journal of Clinical Oncology (2012)

62 Background: Patients (Pts) undergoing radiation therapy (RT) as part of their treatment (Rx) for a malignancy may have pain, distress, anxiety or other problems at the time of initiation of RT. Pts may also develop or have an exacerbation one or more of the above during RT. During RT, pts are seen weekly by the treating physician (MD), and are seen daily by the treating radiation therapy technologists (RTT) as they undergo Rx. Pts may develop problems between weekly MD visits which may benefit from interventions. A system was developed where pts would be asked four questions each treatment day by the RTT: 1) Are you having pain, and if so, how would you rate it on a scale of zero to 10? (PainQ) 2) Are you having anxiety today? (AQ) 3) Are you having new problems or concerns? (ProConQ) 4) Do you want to see the physician today? (CMDQ) This information was used in pt’s management. Methods: 100 pt charts were reviewed for demographics including gender, age, primary malignancy, region treated, number of Rx and radiation dose. The information from the four question instrument was also reviewed for each pt’s course of RT. Results: Of the 100 pts, 56 were male. Disease distribution: Breast-22; Prostate-20; Head and Neck-20; Lung-13; Brain-7; Other-18. For the AQ, 83 did not report anxiety; 17 reported anxiety on one or two occasions. For the ProConQ, 35 reported none, 34 reported yes on 1 or 2 occasions, 22 reported yes on 3 to 5 occasions, and 9 reported yes on greater than five occasions. 29 reported yes on 2 days in a row, and 15 reported yes to problems or concerns on 3 days in a row. For the PainQ, 31 reported no pain throughout their course of RT, with 22, 23, and 25 reporting pain of any magnitude for 1 to 5, 6 to10, and greater than ten days, respectively. 22 reported pain greater than 6 on at least one occasion. For CMDQ, 26 of pts did not request to see the MD, 71 and 3 requested to see the MD an additional 1 to 5, and 6 to 10 times. Conclusions: A simple instrument prompting a four question query to pts undergoing a course of RT may prompt the need for further evaluation and interventions between scheduled MD visits. This may facilitate more expeditious interventions for Rx related toxicity and treatment dependent or independent symptoms or needs.
Homodimerization of Retinoic Acid Receptor alpha through its Fusion Partners Underlies Pathogenesis of Acute Promyelocytic Leukemia.
Authors: Scott C. Kogan, Vernon T. Phan, Thomas Sternsdorf, Mei Lin Maunakea, Jastinder Sohal, Angela Silletto, Francesco Galimi, Ronald M. Evans
Journal: Blood (2004)
Integrated analysis of metastatic disease in clear cell renal cell carcinoma: A collaborative TCGA analysis.
Authors: A. Ari Hakimi, Anders Jacobsen, Roy Mano, Mithat Gonen, Martin Henner Voss, Victor E. Reuter, Kimryn Rathmell, Jodi Kathleen Maranchie, Leonard Joseph Appleman, Pheroze Tamboli, Sabina Signoretti, Toni K. Choueiri, Paul Russo, Robert John Motzer, James Hsieh
Journal: Journal of Clinical Oncology (2014)

432 Background: We sought to identify molecular and genetic features that were associated with metastatic disease at presentation in a cohort of patients derived from the Cancer Genome Atlas (TCGA) ccRCC dataset though our collaborative Clinical TCGA (cTCGA) consortium. Methods: Three hundred forty two patients comprising the cTCGA dataset were further evaluated for additional clinical information including the presence and timing of metastatic disease. Patients with clinical stage I or II disease were excluded. Clinical, molecular and genetic data were obtained and evaluated for their association with metastatic disease at presentation. Using somatic mutations (Exome-seq), DNA copy number (aCGH), mRNA expression (RNA-seq), and miRNA expression (miRNA-seq) data, we inferred molecular and genetic features associated with metastasis. We used random forest and elastic-net statistical learning methods to infer sparse feature combinations associated with metastatic disease at presentation. Results: The study cohort consisted of 147 patients, 81 (55%) of which had metastatic disease at presentation. Median follow was 26 months (Interquartile Range 10, 60) from the time of RCC diagnosis No significant difference in patient gender and age as well as tumor necrosis was found between patients with or without metastatic disease. However, patients with metastatic disease had larger tumors (median diameter 9.2cm vs. 6.8cm, p&lt;0.001), and a higher percent of Fuhrman nuclear grade 3 or 4 disease (85% vs. 71%, p=0.04). Using both statistical learning methods we found that lower expression levels of GARNL3, C1orf172, NEK6 and SLC12A7 and higher expression levels of CEBPD, PITX2 and COMMD5 were associated with metastatic disease at presentation. Conclusions: When evaluating for various clinical, molecular and genetic features, alterations in specific gene expression are associated with metastatic disease in ccRCC patients. External validation in additional data sets is currently underway and further functional studies are required to better understand the therapeutic potential of these genes.
Twenty years of chemotherapy for colorectal cancer (CRC): Progress made, insights gleaned.
Authors: Irfan Jawed, Julia Wilkerson, Austin G. Duffy, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2012)

596 Background: The past 20 years have seen progress in CRC therapy with more effective agents and better medical, surgical and supportive care. Methods: We conducted a systematic review of 101 phase III and large phase II trials in CRC to quantify benefit over time with first-line and subsequent therapies. Outcomes examined in the experimental (EA) and control arms (CA) included progression-free survival (PFS), overall response rate (ORR), stable disease (SD), overall survival (OS) and post-treatment survival (PTS). Data were analyzed according to dates of publication and median enrollment. Results: Significant outcomes are reported; most had R 2 values &gt; 0.6. OS of EA improved 0.83 mos/yr. Importantly the OS of CA improved 0.58 mos/yr likely reflecting use of experimental therapies in CA in subsequent studies and improvement in CRC care over time as suggested by: (1) modest improvements of PFS: 0.33 [EA] and 0.26 [CA] mos/yr; (2) PTS gains of 0.48 [EA] and 0.29 [CA] mos/yr, accounting for majority of OS gains; and (3) lack of OS improvement in 14 second/subsequent line trials. Using logistic regression to examine all drugs as class predictors of increasing OS, oxaliplatin [OX], bevacizumab [BEV], and irinotecan [IRI] were significant in the EA, but only OX and BEV were significant in the CA. Capecitabine [CAP] and cetuximab/panitumumab [CET/PAN] were not significant in EA or CA, with CAP odds ratio towards null and CET/PAN odds ratio away from null. The lack of IRI effect in CA concurs with observation that only IRI regimens had worse OS in CA compared with EA. The CET/PAN results likely reflect lack of efficacy/harm in patients with WT KRAS tumors. As expected PFS and PTS correlate highly with OS, but importantly ORR had very high correlations with both PFS and OS. SD emerged as an “adverse” outcome, OS decreasing as SD rates increase. Conclusions: OS of CRC patients has improved gradually over past two decades, with gains from chemotherapy but also other factors, such as lead-time bias, more loco-regional approaches and improved supportive care. IRI performed better in EA than in CA. CET/PAN had negative effects in the entire population. In CRC, ORR correlates highly with OS, while SD portends a poor outcome.