tbuckley/cabot-search huggingface dataset:
A first catch, non-DRE urine exosome gene signature to predict Gleason 7 prostate cancer on an initial prostate needle biopsy.
Authors: Michael J. Donovan, Mikkel Noerholm, Stefan Bentink, Susan Belzer, Johan Skog, Gordon Andrew Brown, James S. Cochran, Vince O'Neill
Journal: Journal of Clinical Oncology (2015)

45 Background: There is a critical need to reduce initial prostate biopsies (PB) in the PSA ‘gray zone’ of 2-10 ng/mL. Non-invasive screening tools that add predictive value for identifying high-grade, Gleason score (GS) ≥7 should impact on the current diagnostic paradigm. We have developed standardized processes to isolate exosomal-RNA from first-catch urine specimens and sought to identify a gene signature that reliably differentiates GS7+ from GS6 and benign disease. Methods: First-catch non-DRE urine specimens were collected at six sites in standard collection vessels without preservative, stored at 2-8C (up to two weeks) and shipped on ice to a central laboratory (Exosome Diagnostics, St. Paul, MN). Upon receipt, samples were filtered (0.8um), and exosome isolation and RNA extraction performed. RT-qPCR RNA copy numbers of ERG and PCA3, normalized to SPDEF, were measured to generate a three-gene signature, defined to yield a score S between 0 and 30, where S&gt;10 predicts GS7+ vs. GS6 and benign lesions with optimal NPV, Sensitivity and Specificity. Results: Urine samples from 170 men (PSA 2-10 ng/mL, first biopsy,40 mL; median age 62 years, median PSA 5.1 ng/mL, 70% negative DRE, 77%, no family history, 82% Caucasian) of 453 total, with comparable demographics, were evaluated. With 46% and 21% prevalence of positive biopsy for any cancer or GS7+ disease, respectively, a dichotomous gene signature demonstrated good clinical performance in predicting biopsy result. For GS7+, the NPV and PPV were 98.6% and 34.7%, respectively. A continuous score alone had an AUC of 0.76 for discriminating GS7+ from GS6 and benign disease and the results were significantly better than the prostate cancer prevention trial risk calculator (PCPTRC), AUC 0.60. Conclusions: A novel, non-invasive urine exosome gene signature demonstrated independent, negative predictive value for the diagnosis of GS7+ from first biopsy patients with ‘gray zone’ serum PSA. Its use in the biopsy decision process could result in fewer prostate biopsies once validated on an expanded prospective cohort.
Evaluation of the neutrophil-lymphocyte ratio as a predictor of survival after liver transplantation for hepatocellular carcinoma.
Authors: A. R. Limaye, R. Cabrera
Journal: Journal of Clinical Oncology (2011)

170 Background: The Milan criteria are utilized to predict outcomes in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT). Though the survival of these patients has significantly improved since the adoption of these criteria, the risk of recurrence after LT is as high as 20 percent. One limitation of the Milan criteria is the lack of any estimation of tumor biology. The neutrophil-lymphocyte ratio (NLR) has been proposed as a peripheral surrogate for tumor biology. The predictive power of the NLR has been demonstrated for several solid tumors, and early evidence points to a role in HCC. We hypothesize that the NLR is predictive of overall survival and recurrence-free survival in patients with HCC who undergo LT. Methods: This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We defined an elevated NLR as a ratio of five or greater. Results: We identified 160 patients who underwent LT for HCC, 28 of whom had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival for subjects with an elevated NLR (1-year cumulative survival 70% ± 0.08, 3-year cumulative survival 48% ± 0.09, 5-year cumulative survival 38% ± 0.11) was significantly lower than for subjects with a normal NLR (1-year survival 80% ± 0.04, 3-year survival 75% ± 0.04, 5-year survival 68% ± 0.06). On univariate analysis, seven factors (including an elevated NLR) predicted decreased overall and recurrence-free survival. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of overall survival. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of recurrence-free survival. Conclusions: Preoperative NLR is a powerful independent predictor of overall survival and recurrence-free survival in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the MELD score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplant. No significant financial relationships to disclose.
Delays in adjuvant chemotherapy following AP resection for low rectal cancer: Audit results and implications for clinical practice.
Authors: S. S. Nimalasena, A. M. Gaya
Journal: Journal of Clinical Oncology (2011)

562 Background: Abdominoperineal resection (APR) remains the surgical procedure of choice for low rectal cancer. Historically, it has been associated with high rates of postoperative haemorrhage, infection, and wound dehiscence. The perineal wound is particularly at risk, with rates of 16-41% reported. This may delay adjuvant chemotherapy and adversely affect survival. Methods: Patients who underwent APR in our cancer network between March 2009 and June 2010 were identified. Records were reviewed with respect to complications and any impact on adjuvant chemotherapy. Results: 28 patients underwent APR. The majority had Duke's C (68%) and Duke's B (14%) tumors. All received neoadjuvant chemoradiotherapy (CRT) to 45-54Gy with capecitabine 825 mg/m 2 BD. Adjuvant chemotherapy (CAPOX, FOLFOX or capecitabine) was planned in 25/28 (89%) patients. 2 declined, and of the remaining 23, 12 patients (52%) could not receive chemotherapy (Table). Of patients who received adjuvant chemotherapy, the average delay in starting was 2 weeks. At the time of reporting, 25/28 (86%) patients are alive without disease recurrence. One patient who did not receive adjuvant chemotherapy due to wound dehiscence, has recurrent pelvic disease, and is receiving best supportive care. Two patients died of metastatic disease; one could not receive adjuvant chemotherapy due to wound infection. Conclusions: Our audit has highlighted that a significant proportion of patients undergoing APR do not receive adjuvant chemotherapy on time due to wound complications. Often the time taken for wound healing exceeds 3 months, by which time the benefit of chemotherapy is negligible. Phase II studies of neoadjuvant chemotherapy prior to CRT for locally advanced rectal cancer have shown impressive progression-free and overall survival rates, with good compliance rates and favorable toxicity profiles. Further studies are needed. Patients with low rectal tumours who require APR, should be considered for a neoadjuvant chemotherapy approach. [Table: see text] No significant financial relationships to disclose.
A phase I trial of intra-lymph-node administration of a novel immunotherapeutic regimen (MKC1106-MT) in patients with advanced melanoma.
Authors: J. S. Weber, A. Ribas, A. Bot, M. Obrocea, B. Chmielowski, D. Rosario, Z. Qiu, B. Comin-Anduix
Journal: Journal of Clinical Oncology (2010)

8535 Background: MKC1106-MT is an immunotherapeutic consisting of recombinant plasmid pMEL-TYR containing Melan-A (MEL) and tyrosinase (TYR) antigen fragments and 2 peptide (E-MEL; E-TYR) analogs corresponding to an HLA-A*0201-restricted epitopes from each. Methods: Patients received a prime-boost with a fixed priming of the plasmid (2,400 μ g/dose) via ultrasound guided injections into inguinal or axillary nodes on days 1, 4, 15 and 18 followed by peptide on days 29 and 32; cycles were repeated every 43 days. Either 100 mg/dose or 300 mg/dose of each peptide were given. Patients were HLA*0201+, and had stage IIIB/C or IV melanoma positive for MEL and TYR. Clinical evaluations occurred at baseline and the end of each cycle. Patients without disease progression received up to 8 cycles of treatment. Immune responses using PBMCs were measured days 29 and 39 of each cycle by MHC tetramer and IFN gamma ELISPOT for MEL and TYR epitopes. Results: 18 pts were enrolled: 7 in the low dose and 11 in the high dose peptide cohort. Therapy was well tolerated, with no DLTs. No differences in safety or immune responses were seen between the 2 cohorts. The most frequent treatment-related AEs were: fatigue (grade 1-2), chills (grade 1-2) and brief pain at injected sites (grade 1-2). At 1 year, 4 pts, all with nodal metastases showed ORs (1 CR, 2 PRs and 1 SD by RECIST) and all exhibited high baseline levels of MEL T cells. Among two biopsies of regressing lesions one had a dense infiltration of CD8+ T cells with ∼1% TILs being specific for the MEL epitope targeted by MKC1106-MT. Conclusions: Repeated intra-lymph node administration of MKC1106-MT is feasible, safe, induces objective tumor regression and correlates with baseline immunity to MEL. % tetramer MEL+/total CD8+ at baseline (median; range) No OR OR Detectable 4/14 pts ( 0.25; 0.2-0.31) 4/4 pts (0.2; 0.11-0.23) Low/None detectable 10/14 pts (0.06; 0-0.08) 0/4 pts Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Mannkind Mannkind Mannkind
Survivorship care plans for colorectal cancer survivors: What do primary care providers want and need?
Authors: T. Salz, K. C. Oeffinger, P. R. Lewis, R. Rhyne, R. L. Williams, M. W. Yeazel
Journal: Journal of Clinical Oncology (2011)

9131 Background: Colorectal cancer (CRC) survivors face health challenges and poor coordination of care. The Institute of Medicine (IOM) proposed that after treatment completion, oncologists should provide patients with personalized treatment summaries and plans of care to share with their primary care providers (PCPs) to inform ongoing care. We aimed to determine the optimal content of these survivorship care plans by assessing what information PCPs need to care for CRC survivors. Methods: All physicians and mid-level clinicians in two Practice-Based Research Networks in MN and PA were invited to participate in an internet survey between August and December 2010. The survey assessed the need for information about the care of CRC survivors. The IOM‘s proposed survivorship care plan includes 45 topics of information. For each topic, PCPs rated whether they typically receive enough information. Results: 108 (44%) of PCPs responded to the invitation; 87 PCPs were eligible and completed the survey. For 24 (53%) of the topics, at least half of respondents felt they typically had too little information. Most PCPs felt they had too little information about whether there were problems with chemotherapy (70%) and whether the oncologist intended to monitor for other cancers (68%). There was widespread agreement that PCPs do not receive enough information about increased risk of second cancers, other cancers, and other diseases (78%); long-term effects of chemotherapy (72%); long-term effects of radiation (64%); and genetic counseling and testing to identify high-risk individuals (76%). Conclusions: PCPs typically lack information to provide optimal care for their patients who have had CRC. PCPs often need information both about their individual patients and about general survivorship issues. Survivorship care plans which address the treatment history and recommended care for CRC survivors may fill important gaps in PCPs’ knowledge by communicating details of patients’ cancer history and providing general survivorship information. Further, specifying which providers are responsible for different aspects of ongoing care could promote care coordination as survivors navigate between cancer treatment and primary care.
Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.
Authors: Toshimichi Miya, Kunihiko Kobayashi, Mitsunori Hino, Masahiro Ando, Susumu Takeuchi, Masahiro Seike, Kaoru Kubota, Akihiko Gemma
Journal: Journal of Clinical Oncology (2016)

226 Background: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assess efficacy and safety of triple antiemetic therapy consist palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Methods: Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy consist palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication (complete response (CR)) in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication (complete control (CC)). Results: Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Conclusions: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in preventing CINV in patients receiving a carboplatin-containing regimen. Clinical trial information: UMIN000017877.
Clinical trial accrual patterns at a single cancer center: Preliminary results.
Authors: K. N. Souder, Y. Matusov, T. L. Helsten, P. T. Fanta, K. L. Hiner, J. I. Brechlin, L. Bazhenova
Journal: Journal of Clinical Oncology (2011)

e16638 Background: Under 10% of adult cancer patients participate in oncology clinical trials nationwide. More than half of eligible patients are excluded from these trials on the basis of physician decision alone. Low trial participation promotes unrepresentative clinical trial subject populations. We examined clinical trial accrual patterns at the UCSD Moores Comprehensive Cancer Center. Methods: Questionnaires examining a variety of clinical factors were given to lung, breast and gastrointestinal (GI) specialists for every visit in their clinics during Nov. 2010 - Jan. 2011. These and the treating physician’s decision to offer a patient participation in a clinical trial were compared to the availability of clinical trials at our institution during the same period. Multiple regression models were built to examine associations between patient factors, trial availability, and clinician recommendation of clinical trials. Results: We analyzed 432 questionnaires (142 lung cancer visits, 60.6% female; 167 breast cancer visits; 123 GI cancer visits, 51.2% female). About 20% of lung cancer visits had a trial available (9.8% offered participation); a similar trend was seen with GI cancer visits. A trial was available for 13.8% of breast cancer visits (4.8% offered participation). A trial was available more often for those with fewer prior lines of therapy (p=0.03) and higher stage (p<0.001). In 82.6% of visits, there was no available trial. Performance status (PS) was not associated with trial availability (p=0.1) or physician decision to offer participation (p=0.016), but no trials were offered to those with ECOG PS >2. There appeared to be no differences between races, ages, or disease stages with regard to being offered a trial. Visits were not analyzed for repeat patients in this interim analysis. Length of screening, language barriers, and superior standard-of-care treatment were not significantly associated with a physician’s decision not to offer a trial. Conclusions: In this interim analysis, clinical trial accrual trends appear similar across disease groups and offers to participate appear largely based on trial availability. Further work is needed with larger sample sizes and multi-institution experiences.
Prognostic factors for survival in patients with metastatic renal cell carcinoma: a study from the Kidney Cancer Association’s International Kidney Cancer Working Group (IKCWG)
Authors: P. J. Elson, J. B. Manola, M. Mazumdar, J. M. Bacik, S. J. Supers
Journal: Journal of Clinical Oncology (2005)

4533 Background: Numerous well-designed retrospective studies of prognostic factors for survival in patients (pts) with metastatic renal cell carcinoma (mRCC) have appeared in the literature since 1986, however there is no single accepted model for describing survival in this population. This is in part because previous studies have not consistently evaluated the same factors, definitions have varied, and different treatment populations have been studied. Methods: To overcome these difficulties and develop a single validated model for survival in mRCC, the IKCWG has established a comprehensive database of previously reported prognostic factors that are part of the usual pt work-up. The database includes demographic, clinical, pathological, and laboratory data from 3780 pts with previously untreated mRCC who were entered onto institution review board approved Phase I, II, or III clinical trials conducted in Europe and the United States between 1975–2002. Results: 70% of the pts were male, median age at study entry was 57, 86% of pts were ECOG performance status (PS) 0 or 1 and 74% had prior nephrectomy. 72% of pts were treated with interferon alpha (IFN) and/or interleukin-2 (IL-2) alone, or IFN/IL-2-based combination therapies; 25% of pts were treated with chemotherapy alone. 88% of pts have died; median survival was 11.3 months (95% C.I. 10.7–11.8). Using logrank tests, Cox proportional hazards models, and a p=.05 cutoff to identify potential prognostic factors, contributing group, treatment (tx), year on-study, age at diagnosis (dx), race, ECOG PS, recent weight loss, time from dx to on-study, prior nephrectomy, prior radiation, TNM M stage at dx, tumor laterality, the number and sites of metastasis at on-study, histology, grade, and pre-tx WBC, neutrophil count, hemoglobin, sedimentation rate, and serum alkaline phosphatase, albumin and calcium all impact survival. Conclusions: Numerous factors are prognostic for survival in pts with mRCC by univariable analyses. Multivariable analyses to identify which factors are independent predictors and development of a single validated survival model are underway. No significant financial relationships to disclose.
The impact of rhabdoid or sarcomatoid differentiation on kidney cancer outcome.
Authors: J. Wang, N. Yarlagadda, C. Holewinski, M. A. Kessinger
Journal: Journal of Clinical Oncology (2011)

e15188 Background: Clear-cell renal cell carcinoma (RCC) with rhabdoid or sarcomatoid features are rare clinical entities. The current retrospective study sought to define the impact of these pathological features on outcome for RCC. Methods: In reviewing a consecutive series of 458 RCCs who were treated at a single institution between 1997 and 2008, 15 patients of Clear-cell renal cell carcinoma with rhabdoid features (RDRCC) and 35 patients with sarcomatoid change (SRRCC) were identified. Demographic and clinical features, treatment, and survival were compared between RDRCC, RSRCC and those without these features. Differences in cancer specific survival were compared with univariate and multivariate Cox regression analysis. Results: RDRCC and SRRCC were more common in younger than in older patients (p <0.001); more commonly presented with high grade histology (p <0.001) and advanced stage disease (p <0.001). The 3-year cancer specific survival rate was 27.0 %, 25.0% and 73.2% for RDRCC, SRRCC and conventional RCC, respectively. On multivariate analysis there was an increased mortality risk in patients with SRRCC vs RCC (HR 3.69, 95% CI 2.40-5.68, p <0.001); RDRCC vs RCC (HR 4.35, 95% CI 2.22-8.55, p <0.001); Other significant predictor of survival including age at diagnosis (HR 1.03, 95% CI 1.02-1.04, p <0.001); Fuhrman's nuclear grade (HR 1.58, 95% CI 1.07-2.34, p <0.001); tumor stage (HR 2.57, 95% CI 1.78-3.7, p <0.001); and receipt of nephrectomy (HR 0.42, 95% CI 0.30-0.58, p <0.001). Conclusions: Even after adjusting for demographic, pathological and treatment factors, cancer specific survival is significantly worse in patients with SRRCC and RDRCC than conventional RCC.
Breast cancer survival: The association of age within stage of disease.
Authors: C. Parise, K. Bauer, V. Caggiano
Journal: Journal of Clinical Oncology (2011)

1547 Background: Breast cancer survival varies with age, race/ethnicity, and ER/PR/HER2 subtypes. Older, white women tend to have a more favorable form of breast cancer. We have previously shown that there is variation of breast cancer subtypes with age and race/ethnicity. The purpose of this investigation is to determine how survival differs by age among the AJCC pathologic stages. Methods: Using the California Cancer Registry 2001-2008, we examined 92,231 cases of Stages I-III first primary female invasive breast cancers. Five-year relative survival was computed for women younger than 40 years of age, 40-69 years of age, and 70 years and older within each stage. The Log-Rank test was used to compare survival between women ages 40-69 (the largest group) versus older and younger women. Results: There were 63,436 (68.8%) women ages 40-69; 23,120 (25.1%) ages 70 and older; and 5,675 (6.2%) younger than age 40. For Stage I, women ages 40-69 had 99% survival, statistically significantly better (P< 0.0001) than younger and older women. Younger women had the worst survival (95%). For Stage II, women ages 40-69 had the best survival (92%), significantly higher than both younger and older women, who had identical survival at 88%. (P< 0.0001) Survival for women with Stage III cancer was almost identical for women ages 40-69 (75%) and women younger than age 40 (74%) (P > 0.05). Women 70 and older had the poorest survival (66%), significantly worse than the younger age groups (P<0.0001). Conclusions: Women younger than 40 years of age have worse survival than older women in Stages 1 and 2. However, in Stage III, younger women have better survival than women 70 and older. While it is conceded that older women generally have a more favorable form of breast cancer, the gap in survival between older and younger women widens with increasing stage of disease. Caution is advised when making sweeping generalizations regarding breast cancer survival. Variation in breast cancer survival depends on a variety of factors including stage, age, race/ethnicity, and ER/PR/HER2 subtypes.