tbuckley/cabot-search huggingface dataset:
Use of biomakers to predict outcomes of immunotherapy for metastatic renal cell carcinoma
Authors: H. Kim, S. Yi, H. Jun, H. I. Ha, I. Hwang, C. Jung, W. Kim, H. Lim
Journal: Journal of Clinical Oncology (2008)

16015 Background: Metastatic renal cell carcinoma (RCC) is known to have poor and unpredictable course. Moreover, there are no reliable prognostic or predictive molecular markers. The aim of this study is to determine the novel biologic marker which is associated with response to immunotherapy. Methods: Between 1995 and 2006 at Samsung Medical Center, tissue specimens were obtained from 57 patients with metastatic RCC had received combination of high dose interleukin-2 and interferon-α based therapy. Paraffin- embedded RCC tumor samples were immunostained for carbonic anhydrase IX (CAIX) and cyclooxygenase-2 (COX-2) expression to determine predictive or prognostic potential. Results: With median 50 months of follow-up, 57 patients had received median 16 (4–24) weeks of immunotherapy. Forty seven specimens (82.4%) were assessed as clear cell and three (5.3%), four (7.0%), and three (5.3%) patients were classified as sarcomatoid, papillary, and undifferentiated carcinoma. Fourteen out of 17 responding patients (6 complete responses and 11 partial response) exhibited high CAIX (> 85% of tumor cells stained) compared with only 19 of 40 nonresponding patients exhibited low CAIX staining (relative risk, 5.2, 95% CI=1.3–20.8, P=0.02). CAIX immunostaining was an independent prognostic factors for progression free survival in favor of high CAIX immunostaining (adjusted HR=0.31, 95% CI=0.17–0.57, P<0.001). High COX-2 (≥ 50% overall tumor cells stained) contained 10 of 17 (58.8%) responders compared with 7 of 40 (17.5%) nonresponders (relative risk 6.7, 95% CI=1.9–23.8, P=0.004). High COX-2 staining was also an independent prognostic factors for overall survival (adjusted HR=0.23, 95% CI=0.08–0.69). Conclusions: Expression of COX-2 and CAIX seem to be important predictors of outcome in metastatic renal cell carcinoma patients receiving immunotherapy. No significant financial relationships to disclose.
Activation of MYC Pathway Is a Unifying Pathological Event in the Progression from Monoclonal Gammopathy of Undetermined Significance (MGUS) to Myeloma (MM).
Authors: Wee J. Chng, Marta Chesi, Tammy Price-Troska, Greg Ahmann, Kim Henderson, Philip Greipp, Robert Kyle, S. Vincent Rajkumar, Morie Gertz, Rafael Fonseca, P. Leif Bergsagel
Journal: Blood (2007)
Analysis of the results of implementation of a pregnancy screening policy at a comprehensive cancer center.
Authors: Gloria Trowbridge, David Cleveland, Alma Yvette DeJesus, Lee Cheng, Elizabeth Ann Wagar, Charles F. Levenback, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2016)

256 Background: Institutional implementation of a standard pregnancy screening policy for women will enhance the safe and timely delivery of treatment throughout the care continuum. In 2012, we developed and implemented an initial policy on pregnancy screening test (PST). The policy indicated that all providers should fully discuss with their female patients of child bearing potential regarding the potential risks of cancer treatment on fertility and the adverse effects on the fetus. The providers should also discuss the contraceptive options with female patients and their partners prior to diagnostic studies and/or treatment. In 2015, we revised the initial policy to further clarify timeframe for PST and clinical indicators and also developed an algorithm to support this best practice. We assessed practice changes as a result of the policy changes regarding PST at our institution. Methods: A retrospective data review was conducted to assess the number of PST over a 5 year period at The University of Texas MD Anderson Cancer Center. The timeframe includes both baseline and post-implementation policy and reflects annual changes from fiscal year (FY) 2010 to 2015. The pregnancy test was defined as measuring human chorionic gonadotropin (hCG) level in a urine sample. Results: We observed a significant increase in PSTs over time among female patients between ages 10 to 55 years. Over 5 years, there were 23,793 urine pregnancy tests performed. The number of urine pregnancy tests performed per FY were as shown on table below (trend test, p&lt; 0.01). The percentage of PST performed among age groups (years): 1.8% of 10 to 15, 11.6% of 16 to 25, 22.3% of 26 to 35, 34.7% of 36 to 45, and 29.5% of 46-55 years old. Conclusions: Wedemonstrated that developing a standard institutional policy on pregnancy screening tests with further enhancements contributed to a significant increase in the number of PSTs performed over 5 years at our comprehensive cancer center. The majority of PSTs were conducted among female patient between the ages of 26 and 55. [Table: see text]
The role of specific KRAS mutation types in response to treatment by EGFR inhibitors.
Authors: O. Fiala, M. Pesek, L. Benesova, B. Belsanova, M. Minarik
Journal: Journal of Clinical Oncology (2011)

e18006 Background: KRAS mutations can be found in 15 to 25% of lung cancers, frequently in adenocarcinomas and their presence is associated with smoking. The role of KRAS mutations in biological targeted therapy by EGFR inhibitors is ambiguous. While some reports clearly assigned mutated KRAS as negative prognostic factor and negative predictor, others did not confirm such notion. In our work we aimed to elucidate the role of specific type of KRAS mutation in outcome of patients with advanced NSCLC threated with EGFR-TKI therapy. Methods: 443 patients with NSCLC were examined. 38 patients, threated with erlotinib or gefitinib in maintenance setting, were further evaluated. 30 patients were suffering from adenocarcinoma, 7 patients had squamous cell carcinoma including 1 patient with poorly diferentiated carcinoma. 37 patients were smokers and only 1 patient was never smoker. Statistical significance was scrutinized by a Log rank test at a 95% confidence level. Results: KRAS mutation was detected in 66 patients. Glycine to cystein substitution at codon 12 [G12C] was the most frequent type of KRAS mutation, detected in 24 patients. Outcome of patients with G12C [n=24] and patients with other specific type of mutation [nonG12C] [n=14] was compared. Median of TTP in the G12C group was 4,3 weeks in comparison with 9,0 weeks in the nonG12C group [p 0.009]. Median of TTP among patients with adenocarcinoma in the G12C group was 4,1 weeks in comparison with 9,0 weeks in the nonG12C group [p 0.007]. Median of OS in the G12C group was 9,3 weeks in comparison with 12,1 weeks in the nonG12C group [p 0.068], median of OS among patients with adenocarcinoma in the G12C group was 9,3 weeks in comparison with 10,6 weeks in the nonG12C group [p 0.095]. Analysis of OS was influenced by different oncological threatment after EGFR-TKI, different quality of basic supportive care and higher incidence of brain matestasis in the nonG12C group. Conclusions: G12C KRAS mutation is a strong negative predictor for EGFR-TKI threatment. Other specific types of KRAS mutation didn’t prove such a negative predictive value and TTP was comparable to patients bearing wild type KRAS gene.
A multicenter phase II study of docetaxel (D) or docetaxel/gemcitabine (G) weekly in advanced non-small cell lung cancer (NSCLC) in elderly and/or poor performance status (PS) patients (pts).(GFPC 0202)
Authors: H. Le Caer, C. Gimenez, P. Fournel, C. Chouaid, G. Robinet, H. Jullian, A. Vergnenegre, S. Bayle, F. Barlesi, J. R. Barriere
Journal: Journal of Clinical Oncology (2005)

7150 Background: Weekly G and D are both active and well tolerated in elderly pts with NSCLC. However age over 60 and impaired PS measures in oncology are subjective and incomplete. We conducted a non randomized phase II study of weekly D or D/G in elderly and/or poor PS pts in advanced NSCLC; the choice of regimen was determined by age, PS, co-morbidity, 50 pts per arm. Methods: Chemonaive pts with stage IIIB(pleural effusion)/IV, according to table, received D 30mg/m2weekly (arm A) or D 30mg/m2 plus G 900 mg/m2(G only on days 1,8,22,29) (arm B) for 6 consecutive weeks (w), followed by 2 w off, responding and stable pts continued for a maximum of 24 w or until progression. Anaemic pts (haemoglobin<11,5g/dl)received epoietine α 40000 UI weekly. Endpoints were response, time to progression(TTP), safety, quality of life. Results: From Jun 2003 to Nov 2004, 50 pts were enrolled in arm A (47 in arm B). To date 50 pts are avaible in arm A (27 arm B). Patients characteristics: male/female 44/6 arm A, 23/4 arm B; median age 76,6(70–84)arm A, 72,7 (66–82)arm B; median co-morbidity 1,9 (0–5)arm A, 1 (0–4)arm B; PS 2, 32% arm A, 4% arm B;stage IV, 88% arm A, 89% arm B. 39/50 pts evaluable for response rate in arm A; 5 PR (12,8%), 14 SD (35,9%), 20 PD (51,3%); 25/27 in arm B, 11 PR (44%), 10 SD (40%), 4 PD (16%); median TTP and survival 9,2 w/3,8 months (arm A),15 /5,4 (arm B).A total of 68 cycles with a median number of cycles of 1 were administered in arm A, 50 and 1,7 in arm B.The main WHO Grade 3/4 toxicity was fatigue 50% in arm A, fatigue 25,6% and neutropenia 20,5% in arm B.Conclusions: Preliminary analysis suggests that the combination of D and G weekly appears to be promising in elderly pts with mild co-morbidity and good PS . The activity of the D weekly regimen is acceptable, but the high level of early chemotherapy discontinuation confirm the necessary use of comprehensive geriatric assessment in this population. No significant financial relationships to disclose.
Effect of a genomic classifier on adjuvant radiation recommendations after prostate cancer surgery.
Authors: Ketan K. Badani, Darby J. S. Thompson, Christine Buerki, Amar Singh
Journal: Journal of Clinical Oncology (2014)

151 Background: Clinical guidelines recommend adjuvant radiation therapy (ART) after radical prostatectomy in men with adverse pathological features. Practice patterns vary on use of ART. This prospective, multi-center study examines the effect of a genomic classifier (GC) on ART recommendations post-prostatectomy. Methods: A prospective, pre-post tumor-board–like survey was conducted to assess urologists’ treatment recommendations for ART as part of a clinical utility study; results are from a pre-specified interim analysis of 11 unique de-identified cases with adverse pathology. All case histories were based on patients treated by at least one of the urologists participating in the study. Patient age, pathological features, and preoperative prostate-specific antigen were presented to the respondents. Presentation of cases was randomized to minimize recall bias. For each case history, physician respondents first were asked to render an ART recommendation without knowledge of the GC findings (pre-GC); they were then asked to render an ART recommendation after GC findings were provided for the same cases (post-GC). Recommendations were made without knowledge of others’ responses. Results: Twelve urologists at 11 US institutions provided 132 adjuvant therapy recommendations. Pre-GC, ART was recommended in 56 (42%) cases. Thirty three percent (95% CI: 25-41%) of recommendations changed following review of GC results. Among pre-GC recommendations for ART, 39% (95% CI: 27-53%; n=22) changed to observation and among pre-GC recommendations for observation, 8% (95% CI: 3%-17%; n=5) changed to ART. Compared to observation, ART was 11.8 times (odds ratio 95% CI: 2.9 - 46.3) more likely to be recommended for cases with high risk GC scores. Adjuvant therapy recommendations were more strongly influenced by GC score (p=0.0006) than any clinical variable (all p&gt;0.33) when both informed recommendations. Conclusions: Additional knowledge of the tumor’s genomic characteristics, as assessed by GC, results in a statistically significant and clinically meaningful change in treatment recommendations in patients indicated for adjuvant radiation therapy by current clinical guidelines.
Number and location of examined lymph nodes (LN) and survival after resection of node negative non-small cell lung cancer (NSCLC).
Authors: L. E. Miller, R. A. Ramirez, C. Wang, T. O'Brien, A. B. Weir, H. Cole, R. U. Osarogiagbon
Journal: Journal of Clinical Oncology (2011)

e17516 Background: LN metastasis profoundly affects prognosis of patients with resectable NSCLC. Variation in LN examination practice may impact staging accuracy. Evidence from other cancers suggests that patients with fewer examined LN have worse outcome. There is no established threshold number of LN to accurately determine node negativity in NSCLC. The AJCC 7 staging system suggests examination of at least 6 LN, others have suggested 11 to 16. Furthermore, we previously found inferior survival in N1 disease patients without mediastinal LN examination. We examined the impact of varying levels of LN examination in a surgical resection cohort. Methods: Review of all resections for NSCLC in Memphis, TN from 1/1/04 – 12/31/09. Preoperatively treated, pNx, LN-positive, margin positive patients were excluded. Patients were grouped according to AJCC 7 T-stage and sorted by number of examined LN and also by the presence of mediastinal LN in the pathology specimen. Survival was estimated by the Kaplan-Meier method and survival curves were compared by the log-rank test. Results: Majority of resections did not meet the AJCC LN minimum, fewer achieved the 11 lymph node standard (Table). T1 resections with <4 LN had inferior survival (p<0.04). There was a trend towards improvement with examination of greater than 6 and 10 lymph nodes (p>0.05 for all analyses). About 30% of patients of all T-stages had no mediastinal LN examined (Table 1). Patients with T2 and no mediastinal LN examination had significantly worse 5-year survival than those who had mediastinal LN examination (p<0.04). Conclusions: We found no clear association between number of examined LN and survival in this LN-negative resection cohort. The low number of resections attaining high numbers of examined LN may have limited our dataset. In patients with T2N0 disease, resection without mediastinal LN examination significantly impairs survival. N (%) Median # LN (range) > 5 LN (%) > 10 LN (%) N2 LN sampled (%) 5-yr survival with N2 (%) N2 LN not sampled (%) 5-yr survival without N2 (%) T1 391 (51) 5 (1-36) 38 12 66 67 34 63 T2 266 (35) 6 (1-45) 53 17 70 55 30 48 T3 87 (11) 6 (1-30) 51 24 74 37 26 57 T4 24 (3) 4 (1-11) 29 4 63 41 38 0
False-negative rate for HER2 testing in 738 gastric and gastroesophageal junction cancers (GEC) from two global randomized clinical trials.
Authors: David Cunningham, Manish A. Shah, Dustin Smith, Maria Zoudilova, Stephen Paul Hack, Alice Kang, See-Chun Phan, Adrian M. Jubb, Josef Ruschoff
Journal: Journal of Clinical Oncology (2015)

16 Background: False-negative HER2 testing in GEC may deny patients the benefit of HER2-targeted therapy. The aim of this study is to estimate the false-negative rate for HER2 testing in GEC and to evaluate predictive factors that might be used to select patients for re-testing. Methods: Two clinical trials conducted in patients with HER2-negative GEC were conducted by Genentech (NCT01662869 and NCT01590719). Information on local HER2 results was collected and testing was repeated centrally by immunohistochemistry (IHC; Ventana, 4B5 antibody) and FISH. HER2 positivity was determined using published criteria (Mod Pathol 2012;25:637). Results: Of 1,189 patients screened, 738 GECs were HER2 negative by local testing and had central results available. Twenty-nine patients (3.9%, 95% confidence interval [CI] 2.5–5.3) were locally HER2 negative, but centrally HER2 positive. The cases showed a wide geographic distribution, a mixture of biopsies (n=19) and resections (n=10), and a mixture of gastric cancer (n=20) and GEC (n=9). All false-negative cases were centrally confirmed to be Lauren’s intestinal (n=25) or mixed (n=4) morphology; amongst intestinal/mixed GEC, the false-negative rate was 6.4% (95% CI 4.1–8.6). Detailed local testing results were available for 25 cases, of which 21 cases showed local IHC scores of 0 or 1+ but were centrally IHC 2+/FISH positive (n=17) or IHC 3+ (n=4). The remaining 4 cases were locally HER2 IHC 2+, FISH negative, but centrally IHC 2+, FISH positive. Conclusions: A clinically significant false-negative rate of 6.4% was observed for HER2 testing in GEC (intestinal/mixed type). Several measures might improve the accuracy of HER2 testing, including running FISH and IHC on all cases, carefully evaluating internal positive controls, improving the education of pathologists, and retesting cases with mixed or intestinal morphology. Clinical trial information: NCT01590719 and NCT01662869.
An interactive video-based approach to diet education for patients posthematopoietic stem cell transplantation.
Authors: Sara Close, Amy Emmert, Robert Soiffer, Edwin Alyea, Joseph Harry Antin, Brett Glotzbecker
Journal: Journal of Clinical Oncology (2016)

183 Background: Hematopoietic stem cell transplantation (HCT) is a complex process in which patient education is increasingly recognized as a critical element to enhance patient preparedness and survivorship. Diet-related education to prevent infectious complications is an essential part of HCT care. Current teaching methods include one-on-one clinician/patient discussion supported with printed materials. Video based teaching may strengthen the learning process of patients and their caregivers. The audio and interactive components may be particularly useful in older patients as sensory ability declines with age. Methods: Focus group methodology was utilized. Four groups of patients, nurses, physicians, pharmacists and dietitians were asked semi-structured questions to allow for collection of systematic data. Multiple rounds of content analysis were used to eliminate duplicates and identify common themes. An interactive video based on items identified and institutional protocols was developed. After refinement of both content and usability, the video was presented to 10 patients and their caregivers admitted to the hospital for HCT. They were instructed on its use and given unlimited time to view it. A survey was conducted by a member of the HCT team to collect feedback regarding length and content of the program. Results: All patients felt the program was a helpful supplement to the written materials. They also felt that the content was consistent and the program was easy to use. Two patients said the video was long, though commented positively on how comprehensive it was. One patient preferred printed materials to have during food preparation. All patients requested that the video be available to view after discharge. Conclusions: Feedback from a multidisciplinary team was instrumental in the development of an interactive tool reviewing post-HCT nutrition guidelines. Feedback from an initial cohort of patients has been positive in regards to usability and knowledge gained. This video will enhance patient and caregiver education and allow them the ability to take an active role in their HCT care. Next steps include a more formal evaluation of clinical outcomes related to this method of learning.
Randomized phase II trial of docetaxel plus prednisolone with or without androgen deprivation treatment in castration-resistant prostate cancer.
Authors: Jae Ho Jeong, Hyejung Hyun, In Gab Jeong, Jun Hyuk Hong, Hanjong Ahn, Jae-Lyun Lee
Journal: Journal of Clinical Oncology (2016)

217 Background: Androgen deprivation therapy (ADT) has been the main treatment option for patients with locally advanced or metastatic prostate carcinoma. However, the impact of continued ADT on clinical outcomes in castration-resistant prostate cancer (CRPC) patients treated with cytotoxic chemotherapy is controversial. We conducted a randomized phase II study to assess the impact of continued ADT in patients with CRPC receiving docetaxel plus prednisolone chemotherapy. Methods: Patients with CRPC were randomly assigned (in a 1:1 ratio) to receive docetaxel (75mg/m 2 every 3 weeks) plus prednisolone (5mg twice daily on days 1-21) with ADT (leuprolide 11.25 mg long-acting depo every 12 weeks, ADT group) and docetaxel plus prednisolone without ADT (No-ADT group). For patients in the No-ADT group, ADT was resumed at the end of chemotherapy. The primary endpoint was time to PSA progression. Secondary objectives included PSA response rates, progression-free survival (PFS), and overall survival (OS). Suspension of leuprolide support prevented the attainment of our original goal of enrolling 80 men. Results: Between April 2011 and July 2014, 45 patients were enrolled in this study; 23 patients were randomly assigned to the ADT group and 22 to the No-ADT group. The median age was 68 years (range = 49-81) and median baseline serum PSA was 60.3 ng/mL (interquartile range = 14.7-157.3). Time to PSA progression was 6.5 months in ADT group and 4.3 months in No-ADT group, respectively (P = 0.673). PSA response rates were 55.2% and 44.8% in the ADT group and the No-ADT group, respectively (P = 0.463). The median PFS and OS were 5.3 months and 19.4 months for ADT patients and 4.3 months and 20.8 months for No-ADT patients, respectively (P = 0.608, P = 0.635). The testosterone level rose to more than the castrate level in 5 (22.7%) patients of the No-ADT group. Conclusions: Clinical outcomes were not signiﬁcantly different when patients with CRPC received concurrent ADT, or were not so treated, when receiving docetaxel plus prednisolone chemotherapy. Clinical trial information: NCT01487902 Clinical trial information: NCT01487902.
A clinical perspective on the 2016 WHO brain tumor classification and routine molecular diagnostics
Authors: Martin J. van den Bent, Michael Weller, Patrick Y. Wen, Johan M. Kros, Ken Aldape, Susan Chang
Journal: Neuro-Oncology (2017)

The 2007 World Health Organization (WHO) classification of brain tumors did not use molecular abnormalities as diagnostic criteria. Studies have shown that genotyping allows a better prognostic classification of diffuse glioma with improved treatment selection. This has resulted in a major revision of the WHO classification, which is now for adult diffuse glioma centered around isocitrate dehydrogenase (IDH) and 1p/19q diagnostics. This revised classification is reviewed with a focus on adult brain tumors, and includes a recommendation of genes of which routine testing is clinically useful. Apart from assessment of IDH mutational status including sequencing of R132H-immunohistochemistry negative cases and testing for 1p/19q, several other markers can be considered for routine testing, including assessment of copy number alterations of chromosome 7 and 10 and of TERT promoter, BRAF, and H3F3A mutations. For "glioblastoma, IDH mutated" the term "astrocytoma grade IV" could be considered. It should be considered to treat IDH wild-type grades II and III diffuse glioma with polysomy of chromosome 7 and loss of 10q as glioblastoma. New developments must be more quickly translated into further revised diagnostic categories. Quality control and rapid integration of molecular findings into the final diagnosis and the communication of the final diagnosis to clinicians require systematic attention.