tbuckley/cabot-search huggingface dataset:
Survival for patients with residual tumor at radical cystectomy following chemotherapy: A matched analysis to cystectomy-only patients.
Authors: Bimal Bhindi, Igor Frank, Ross Mason, Robert F. Tarrell, Prabin Thapa, John C. Cheville, Brian Addis Costello, Lance C. Pagliaro, Jeffrey Karnes, Robert Houston Thompson, Matthew K. Tollefson, Stephen A. Boorjian
Journal: Journal of Clinical Oncology (2017)

355 Background: While neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) improves survival compared to RC alone for urothelial carcinoma of the bladder (UCB), the bulk of this survival benefit has been attributed to patients who achieve ypT0 status at RC. The implications of having residual UCB (rUCB) at RC after NAC are less clear. As such, we evaluated whether the outcomes for patients with rUCB after NAC differ from stage-matched RC patients who did not receive NAC. Methods: Patients undergoing RC for UCB between 1981-2010 at Mayo Clinic were identified. All RC pathology was re-reviewed by a single genitourinary pathologist. Patients who received NAC were matched 1:2 to patients not exposed to NAC based on pT and pN-stage, margin status, and year of RC. Kaplan Meier and Cox regression analyses were used to evaluate the associations between NAC and cancer-specific (CSS) and overall survival (OS), stratified by presence of rUCB (i.e. (y)pT0N0 and non-(y)pT0N0). Results: We matched 111 patients who underwent NAC + RC to 222 RC-alone patients. Median age was 68 years (IQR 60,74); 59 (18%) were female. Median follow-up among survivors was 7.2 years (IQR 6,16). A total of 248 patients died; 148 died from UCB. In patients without rUCB at RC, there were no differences in 5-yr CSS (86% vs. 90%, p=0.85) or OS (82% vs. 84%, p=0.46) between patients who did and did not receive NAC. Moreover, on multivariable analysis, NAC exposure was not associated with CSS (HR=1.0; 95%CI 0.3-3.1; p=0.9) or OS (HR=0.9; 95%CI 0.4-1.9; p=0.8) in this subgroup. Among patients with rUCB, receipt of NAC was associated with significantly worse 5-yr CSS (32% vs. 56%, p&lt;0.001) and OS (25% vs. 48%, p&lt;0.001). NAC exposure remained independently associated with worse CSS (HR=2.2; 95%CI 1.6-3.1; p&lt;0.001) and OS (HR=2.0; 95%CI 1.5-2.7; p&lt;0.001) among these patients. Conclusions: While patients who achieve a complete response to NAC have excellent survival outcomes, patients with residual UCB at RC after NAC have a worse prognosis compared to stage-matched RC patients not exposed to NAC. Such patients should be considered for enrolment in novel adjuvant therapy trials.
Pathologic response and disease-free survival (DFS) after neoadjuvant trastuzumab (T) for HER2+ breast cancer (BC): Results from the National Cancer Institute (NCI) of Mexico.
Authors: Cynthia Mayte Villarreal-Garza, Enrique Soto-Perez-de-Celis, Erika Sifuentes, Yanin Chavarri Guerra, Santiago Ruano, F. Berenice Baez-Revueltas, Fernando Lara-Medina, Jose Antonio Acevedo
Journal: Journal of Clinical Oncology (2013)

e11533 Background: The most accurate definition of pathologic complete response (pCR) in HER2+ BC patients (pts) receiving T-based neoadjuvant chemotherapy associated with improved DFS is controversial, particularly regarding the role of residual ductal carcinoma in situ (ypTis) and focal invasive residuals (ypT1mic). The effect of pCR on DFS in various subgroups of HER2+ BC is also uncertain. Methods: Pts with localized HER2+ BC that received T-based neoadjuvant chemotherapy at NCI between January 2007 and May 2012 were identified. We conducted an exploratory analysis of DFS in pts according to their tumor response. DFS curves were derived from Kaplan-Meier estimates and compared by log-rank test. Multivariate analysis was performed using Cox’s regression model. Results: 243 pts were included for analysis. Median follow-up was 39 months (mo). 49% of pts had no invasive and no in situ residuals at surgery (ypT0), 14.4% had ypTis/ypT1mic residuals and 36.6% had gross residual BC. DFS was significantly superior in pts with both ypT0 and ypTis/ypT1mic (no gross invasive residual BC) compared with those with gross residual disease (60.6 and 62.7 mo respectively vs. 51.6 mo, p=0.011 and 0.017). There was no difference in DFS between ypT0 and ypTis/ypT1mic pts (p=0.402). The rate of no gross invasive residual BC was significantly superior in pts with ER-PR- tumors compared with patients with ER+/PR+ tumors (69.9% vs. 56.7%, p=0.034). No gross invasive residual BC was associated with improved DFS in pts with HER2+ ER-/PR- (60.3 vs. 49.0 mo; p=0.005), as opposed to HER2+ ER+/PR+ tumors (61.0 vs. 51.6 mo; p=0.100). Multivariate analysis showed that tumor size (p=0.013) and no gross invasive residual BC (p=0.13) were associated with improved DFS in all subgroups. Conclusions: The absence of gross invasive residual BC was associated with improved DFS in pts with HER2+ BC treated with T-based neoadjuvant chemotherapy, particularly in those with HER2+ ER-/PR- BC. Our data suggest a comparable DFS in HER2+ BC patients with no gross invasive residual BC regardless of the presence or absence of both ypTis and ypT1mic disease after neoadjuvant treatment.
Prognostic factors and scoring model for survival in advanced biliary tract cancer.
Authors: Hyung Soon Park, Ji Soo Park, Yun Ho Roh, Jieun Moon, Dong Sup Yoon, Hei-Cheul Jeung
Journal: Journal of Clinical Oncology (2017)

264 Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ 2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( &lt; 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P &lt; 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P &lt; 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P&lt; 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection.
Predictive factors for chemotherapy feasibility in elderly patients with solid tumor: Results of GERCOR old prospective multicenter study.
Authors: Elisabeth Carola, Benoist Chibaudel, Stephanie Trager, Leïla Bengrine-Lefèvre, Joelle Chuzel, Jean Francois Seitz, Patrick Dion, Pascal Artru, Nasredine Aissat, Emmanuelle Sarlon, Florence Woerth, Mélanie Gauthier, Franck Bonnetain, Aimery de Gramont
Journal: Journal of Clinical Oncology (2013)

9511 Background: One quarter of patients with cancer are 75 year old and over. Previous studies suggested that geriatric parameters improved survival in elderly patients with solid advanced cancer and chemotherapy severe toxicity. A simplified scale would be helpful for oncologist to predict chemotherapy feasibility. The aim was to identify geriatric predictors of chemotherapy feasibility in chemo-naïve elderly patients. Methods: We conducted a prospective multicenter cohort study (NCT00664911). Inclusion criteria were: ≥ 75 years, solid tumor, able to receive at least 2/3 of the standard dose at the first course of treatment. Ten geriatric parameters were recorded at baseline by the oncologist: 1-three words test, 2-date and address for cognitive function, 3-Instrumental Activities of Daily Living (IADL), 4- monopodal stand-up test, 5-hospitalization during the previous year, 6-number of medicines taken for comorbidities, 7-creatinine clearance, 8-albumin serum level, 9-self-rated depressive mood question and 10-presence of a caregiver. The main outcome was chemotherapy feasibility defined by the ability to receive at least 3 months of the planned therapy. Multivariate logistic regression was used. Results: 576 patients were included in 49 centers from 2008 to 2012, 516 (89.6%) were eligible for analysis. Mean age was 81 years, 50.6% had colorectal cancer, 69.5% advanced stage and 83.6% had performance status 0-1. Chemotherapy feasibility was observed in 298 (57.8%) patients. Grade 3-4 toxicity was observed in 26.2% of patients. In multivariate analysis albuminemia &lt; 30g/l (adjusted OR =2.34 CI95% [1.43-3.83]) and depressive mood (adjusted OR=1.55 CI95% [1.02-2.35]) were significantly associated with chemotherapy unfeasibility whereas others geriatrics parameters were not. Conclusions: Albuminemia and self rated depressive mood status were independently predictive for chemotherapy feasibility in elderly patients with solid tumor. Unexpectedly others geriatrics parameters were not independent predictors. Clinical trial information: NCT00664911.
Recurrent parathyroid carcinoma and the need for molecular profiling to aid in prognostication and therapeutics.
Authors: Lily Kwatampora, Callisia Clarke, Angelica Silva, Yildiz Zorba, Michelle D. Williams, Russell Broaddus, Gary L. Clayman, Adel K. El-Naggar, Robert F. Gagel, Elizabeth Gardner Grubbs, Mouhammed Amir Habra, Mimi I-Nan Hu, Camilo Jimenez, Scott Kopetz, Jeffrey Edwin Lee, Steven I. Sherman, Rena Vassilopoulou-Sellin, Steven Waguespack, Nancy D Perrier, Naifa Lamki Busaidy
Journal: Journal of Clinical Oncology (2015)

e17012 Background: Parathyroid carcinoma (PC) is rare, has high morbidity and poor overall survival. Surgery is the mainstay of treatment but recurrence is common. There are no known therapeutic options and efforts to ascertain prognostic factors are restricted by rarity of disease. We report the largest single institution experience and aim to identify prognostic clinicopathologic features associated with aggressiveness of disease. Methods: Retrospective review of PC patients from 1981 to 2014 at a tertiary cancer center was done. Those with a final pathology diagnosis of carcinoma, atypia or neoplasm on were included. Clinicopathological data was analyzed for predictors of disease recurrence. Limited molecular profiling on a subset of patients was done. Cox regression was used for univariate analysis with p ≤ 0.05 considered significant. Results: 87 patients met inclusion criteria. Median follow up was 5 yrs [IQR 3-8]. 36 patients (41%) underwent local resection, while 48 (55%) had en bloc resection. 30(35%) developed recurrent or persistent disease with > 85% requiring ≥ 3 surgeries for palliation or cure. Univariate analysis of clinicopathological data showed only mitotic index (MI) of ≥ 1 was predictive of disease recurrence (PFS) (p = 0.03) with a trend towards decreased overall survival (OS) (p = 0.06). Extent of initial surgery had no bearing on PFS or OS. 8 patients with recurrent disease had molecular profiling. 2 had no discernible mutations, 2 had TP53 mutation. Others mutations identified were CDC73, CTNNB1, KDM5C, NF1 and TLR4. Conclusions: High MI is prognostic of disease recurrence in PC. Radical resection at initial surgery did not improve PFS. Other clinicopathologic features of PC fail to precisely identify risks for recurrent disease. In the subset of patients with limited therapeutic options, genomic profiling is needed to identify prognostic and targetable mutations and drive research aimed at creating novel therapeutics. Variables Values median [IQR] Age (yr) 58 (47-66) Gender n(%) Male 34(39) Female 53(61) Final Pathology n(%) Carcinoma 56(64) Neoplasm 17(20) Atypia 10(12) PTH at diagnosis (pg/ml) 381 [203-1536] Ca+ at diagnosis (mg/dl) 12.9 [12-14.5] 10 year OS 67% 10 year PFS 56%
A phase I and pharmacokinetic study of continuous infusion EMD 121974 (EMD), an antiangiogenic αvβ3 and αvβ5 integrin antagonist, in patients with advanced solid malignancy
Authors: S. D. Undevia, L. Janisch, W. M. Stadler, S. M. Wittemer, M. J. Ratain
Journal: Journal of Clinical Oncology (2006)

3052 Background: Integrins αvβ3 and αvβ5 are cell-surface receptors that play a significant role in angiogenesis by mediating the ligation signal that allows endothelial cells to attach to the extracellular matrix. These integrins share the binding epitope Arg-Gly-Asp (RGD). EMD is an RGD-containing cyclic pentapeptide. In clinical studies to date, EMD has been administered in an intermittent fashion. However, EMD has a short half-life of 3–5 hours with no evidence of drug accumulation. These data prompted the initiation of this phase I study of continuous infusion EMD. Methods: EMD was administered as a continuous infusion without break in 4-week cycles. Plasma samples for pharmacokinetic studies were obtained weekly in cycle 1 immediately prior to and 2 hours after infusion bag change. Results: To date 21 patients (15 male/6 female, median age 56, median Karnofsky performance status 90%) have been treated at the following dose levels: 1, 2, 4, 8, 12, 18, and 27 mg/h. Hematologic toxicities have been limited to grade 2 anemia and grade 3 lymphopenia. Non-hematologic toxicities have been limited to grade ≤ 2 and include alopecia, anorexia, diarrhea, fatigue, hypokalemia, hyponatremia, hypophosphatemia, insomnia, mucositis, nail changes, nausea, and transaminase elevation. One patient treated at 27 m/h experienced an unobserved death of unknown cause after two weeks of therapy. Pharmacokinetic analysis has been completed for patients treated at the 12 mg/h dose level and below. Mean values for half-life, clearance, and volume of distribution were comparable across dose levels, and steady-state concentration increased proportionally to dose. Conclusions: EMD can be safely administered as a continuous infusion at doses of up to at least 18 mg/h. No single toxicity has been consistently observed. A patient death in cycle 1 has resulted in the expansion of the 27 mg/h dose level. The pharmacokinetics of continuous infusion EMD were predictable and in general agreement with the published data of twice weekly infusion. Study enrollment is ongoing. [Table: see text]
Association of Notch-1 phenotype with clinical stage progression in non-small cell lung cancer.
Authors: Sherry X. Yang, Larry Rubinstein, Dat Nguyen, Joseph E. Tomaszewski, Naoko Takebe, Percy Ivy, James H. Doroshow
Journal: Journal of Clinical Oncology (2014)

e22123 Background: The Notch signaling pathway is crucial in context-dependent cell fate determination that has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). Notch-1 regulates tumor cell survival by promoting growth and suppressing apoptosis. We and others have previously shown that Notch-1 is expressed in about 50% of NSCLC. However, the role for Notch-1 on tumor progression remains to be defined. Methods: Expression of Notch-1 was examined by immunohistochemistry on 55 cases of NSCLC with stage I to III primary tumors. Levels of Notch-1 expression were quantitatively scored with assistance of an Automated Digital Imaging System. Association between Notch-1 expression and clinicopathological parameters was assessed by the Pearson statistic or Spearman rank order correlationtest. All P values are two-sided. Results: Tumor Notch-1 expression was not significantly associated with tumor differentiation, tumor size, and demographics including age and sex. In contrast, Notch-1 expression was negatively associated with clinical stage and nodal status (r = -0.33, P = 0.009 and r = -0.30, P = 0.02). Notch-1 expression in stage I disease (median staining index 5, range 0 to 60) was higher than in stage II/III diseases (0.9, 0 to 5; P= 0.03 by the Wilcoxon nonparametric rank test). Conclusions: The Notch-1 phenotype is inversely associated with clinical stage progression primarily driven by the nodal status but not tumor size. Notch-1, frequently overexpressed in NSCLC, may be a marker of non-metastatic propensity. Our results suggest the importance of detection of the target presence and early application of efficacy biomarkers when targeting the Notch signaling in advanced NSCLC due to the tendency of decreasing Notch-1 phenotype following tumor progression. The data might have relevance for targeting the Notch signaling pathway in early stage lung cancer.
Symptom burden in long-term head and neck cancer survivors.
Authors: Gaia Pocobelli, Rebecca Ziebell, Monica Fujii, Jennifer McClure, Jessica Chubak
Journal: Journal of Clinical Oncology (2017)

124 Background: The symptom burden faced by long-term head and neck cancer survivors could inform clinical decision making but it is not well understood. Methods: In 2016 we surveyed current enrollees of Group Health (an integrated health care delivery system in Washington State) who were aged ≥18 years when diagnosed with head and neck cancer in 2011 (n = 54). Symptoms experienced in the past 24 hours were assessed using the validated MD Anderson Symptom Inventory head and neck cancer module (MDASI-HN). Survivors were asked to report on a 10-point scale the severity of the problem at its worst (“not present” to “as bad as you can imagine”). Self-reported risk factor and demographic information were also collected. Results: Eighty percent of persons responded to the survey (n = 43) via web questionnaire (n = 12), mailed questionnaire (n = 26) or telephone interview (n = 5). One person who reported to have not been diagnosed with head and neck cancer was excluded, leaving 42 participants. Overall, 29% had no more than mild symptoms (all MDASI-HN symptoms rated &lt;5 ), 43% had no more than moderate symptoms (all MDASI-HN symptoms rated &lt;7 ), 57% had one or more symptoms rated as severe (at least one MDASI-HN symptom rated ≥7 ), and 45% had two or more symptoms rated as severe. The symptoms most commonly rated as severe were: dry mouth (38%), difficulty swallowing or chewing (17%), pain (17%), fatigue (17%), disturbed sleep (15%), feeling sad (15%), choking or coughing (15%), problems with tasting food (15%), problems with teeth or gums (15%), problems with mucus in the mouth or throat (12%), and feeling distressed (12%). Persons who rated one or more symptom as severe were more likely than those who did not to have had cancer recurrence (44% versus 6%), receipt of cancer treatment in the previous three years (36% versus 17%), age ≥65 years at diagnosis (63% versus 17%), non-white race (21% versus 6%), no more than high school education (33% versus 17%), current unemployment/disability/retirement (71% versus 44%), and annual household income &lt;$100,000 (71% versus 56%). Conclusions: In the context of limited data on this topic, in this small study we found that it was not uncommon for five-year survivors of head and neck cancer to experience one or more symptoms which they rated as being a severe problem.
Quantitative assessment of melanoma spread in sentinel and non-sentinel lymph nodes and survival.
Authors: Anja Ulmer, Klaus Dietz, Hans-Martin Haefner, Helmut Breuninger, Claus Garbe, Martin Röcken, Friedegund Elke Meier, Gerhard Fierlbeck
Journal: Journal of Clinical Oncology (2014)

9082 Background: We have recently shown that quantification of cancer dissemination from melanoma to sentinel nodes is feasible and can be combined with other characteristics of the primary tumor to improve outcome prediction. Here we asked whether quantitative assessment of cancer spread to non-sentinel nodes could further improve outcome prediction. Methods: The study includes 128 melanoma patients with microscopic positive sentinel nodes who underwent complete lymph node dissection at the University of Tübingen. We analyzed 267 sentinel nodes and 1129 non-sentinel nodes from these patients by pathology and by quantitative immunocytology. For immunocytology half of the node was disaggregated mechanically, single cell suspensions were dispensed onto slides, stained with the melanoma specific antibody gp100. For each node we recorded the disseminated cancer cell (DCC) density, defined as the number of gp100 positive cells per million lymph node cells examined. Results: Quantitative immunocytology showed melanoma spread in non-sentinel nodes in 101 of 128 patients (79%), pathology was positive in 23 of 128 patients (18%). At a median follow-up of 67 months (range 3 to 136 months) 45 patients (35%) had died from melanoma. DCC densities in the sentinel node predicted outcome by univariable and multivariable analyses. Additional quantitative assessment of DCC densities in non-sentinel nodes did not significantly improve outcome prediction. A model based on DCC density in the sentinel node and thickness of melanoma predicted outcome even more precisely than a model based on the current AJCC staging system that includes information about the total number of histopathologically positive nodes. Conclusions: Quantitative reporting of the sentinel node status allows accurate prediction of melanoma outcome without knowledge of the status of non-sentinel nodes. Routine measurement of DCC densities in sentinel nodes may improve patient stratification for clinical trials and facilitate treatment decisions at the time of sentinel node biopsy when the complete nodal status is unknown.