tbuckley/cabot-search huggingface dataset:
Protein profiles (proteomics) discriminating between relapses versus relapse-free survival after adjuvant tamoxifen in 272 patients with primary estrogen receptor (ER) and progesterone receptor (PgR) positive breast cancer
Authors: B. K. Linderholm, J. Lehtio, A. Ploner, Y. Pawitan, L. Skoog, R. Lewensohn
Journal: Journal of Clinical Oncology (2004)

9615 Background: Expression of estrogen- (ER) and progesterone receptors (PgR) are predictive factors for effect by endocrine therapy, with highest response rates in patients with a both ER and PgR pos. breast cancer (BC). We have shown that overexpression of c-erbB-2, high expression of VEGF or of VEGFR2 significantly correlate with shorter survival times after adjuvant endocrine therapy in ER and PgR positive BC. Material & Methods: A total of 404 patients with primary operable BC diagnosed 1993 to 1996 received adjuvant endocrine therapy manly tam for 2 or 5 years. Of these 295 patients had a both ER and PgR positive BC, 23 received goserelin and were excluded, leaving 272 patients for proteomics analyses. No patients received adjuvant chemotherapy, median age 64 years (29 to 92), median follow-up time 94 months. Protein profiles were determined by use of Surface Enhanced Laser Desorption /Ionisation Mass spectrometry (SELDI-MS) technology. Samples were run in duplicate; cation exchange array pH 5.0 and anion exchange array pH 5.0, low and high intensity runs. Results: A pilot study was performed consisting of 16 cases; 8 patients with fast relapses (<2 years) (R) and 8 controls (C) with long relapse-free survival times which were matched for tumor size, lymph node metastasis, histological grade and age. Five putative biomarkers were found separating patients in the two groups from each other. Three proteins were over-expressed in relapsing patients compared with relapse-free (mean relapsing 1.39, mean control 0.52; p-value 0.0025), (mean R 2.39, mean C 1.17; p=0.00008), and (mean R 4.05, mean C 2.95; p=0.02) respectively. Two proteins were significantly lower expressed in relapsing patients (mean R 1.86, mean C 3.74; p=0.0019) and (mean R 3.39, mean C 5.14; p=0.0074) respectively. Conclusion: Preliminary data suggest 5 putative biomarkers separating ER and PgR positive patients with effect/no effect from adjuvant tam. Data on a validation set consisting of 80 patients and validation in the total patient population will be presented. No significant financial relationships to disclose.
Validation of observed savings from an oncology clinical pathways program.
Authors: Jeffrey A. Scott, Scott Milligan, Winston Wong, Daniel Winn, Joseph Cooper, Neil Schneider, Sheamus Parkes, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2013)

6553 Background: Oncology clinical pathways have been suggested as a way to decrease cancer treatment variation and costs. CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions to launch the first cancer clinical pathway in the US in Aug 2008. Savings from that program were reported by Scott et al, ASCO 2010. The purpose of this study was to obtain third-party validation of the observed savings of this pathways program. Methods: We used CFBCBS claims data from Jan 2007 to Dec 2010 to identify patients (pts) with breast, colon, or lung cancer who were treated by physicians participating in the pathways program. We used Truven Health’s MarketScan database to retrospectively identify a control group treated by non-institutional physicians in a similar geographic region outside the CFBCBS network. We further balanced the groups using propensity score weighting to align primary diagnosis and demographics. The primary outcome was the sum of allowed cancer costs for 270 days after a patient’s first chemotherapy treatment. A secondary outcome was the probability of an inpatient (inpt) admission over the same time period. Many generalized linear models were fit for sensitivity testing. Boosted decision tree models were also used to fully capture all nonlinearities and interactions. Both types of models use the propensity score weights. All savings estimates were based on comparing trends between cohorts. Results: A total of 2424 CFBCBS pts were included in the analysis. The aligned control group consisted of 1490 pts. The treatment coefficient from the linear model for the primary outcome was -0.16 with a z-value of -3, which translates to a savings estimate of 15% for the program. The treatment coefficient from the logistic model for the secondary outcome of inpt admission reduction was -0.29 with a z-value of -2.5, which translated to a 7% reduction (from 50% to 43%) in hospital admissions. The boosted decision tree models confirmed results of a more moderate magnitude. Conclusions: We conclude that the CFBCBS pathways program saved upwards of 15% on cancer-related claims costs with a 7% reduction in the probability of an inpt admission. These findings are consistent with those previously presented and peer reviewed.
Permanent prostate brachytherapy and short-term androgen deprivation for favorable and unfavorable intermediate risk: Clinical results for median 5 year follow-up.
Authors: Stephane Gilles Guerif, Sarah Molina, Guillaume Hugues, Odile Boissonnade, Bertrand Debaene, Gaelle Fromont, Antoine Berger
Journal: Journal of Clinical Oncology (2017)

e554 Background: The option of prostate brachytherapy for intermediate risk is discuss. We present mature results of permanent prostate brachytherapy and short-term androgen deprivation for favourable and unfavourable intermediate risk. Methods: From 01/2006 through 12/2012, 707 patient were treated by real time iodine brachytherapy. 135 intermediate risk, 72% favourable and 28% unfavourable were include. Unfavourable was define as a gleason 7 (4+3) or &gt; 50 % positive biopsy or 2 intermediate factors. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 94% patients. 91 % of patients have a duration of hormone ≤ 6 mouths. 40% had vesicle seminal biopsy. 62 % had a lymph node dissection. 75 % had a bone scan. 95% had a MpMRI with tumour index in 72 %. All patients with DIL on MpMRI had a focused real time image guided brachytherapy. Tumour control was measure with phoenix definition and death with Kaplan-Meier method. The GU and GI toxicity were measure with IPSS and CTCAE V 3, IIEF-5. Results: The mean Number of seeds used was 63 ( SD, 13). Mean prostate volume was 27 cm3 (SD, 11) and 70cc maximum. Mean dose to 90% of the prostate was 188 Gy (SD, 9). Ud30 (mean, 189 Gy; SD, 10). RD2cc (mean, 105Gy; SD, 22). Mean duration of hormone was 5,6 mouths (SD,1,6). The biologic disease free survival at 5 and 8 years were 97,1 % and 94%. The global survival at 5 and 8 years were 98%. The urinary symptoms return to the baseline at 2 years with maximum toxicity at 1 month. 2 GU grade 3. GI grade 1 2 and 3 were 34%, 15% and 0%. 20% of patients with IIEF &gt; 16 at baseline had sexual intercourse at Two years. Conclusions: Our single-institution study with a median 5-year follow-up showed that permanent prostate brachytherapy and short-term androgen deprivation risk was safe and effective for patients with favourable and unfavourable intermediate risk prostate cancer. However the association of hormone decrease the sexual function. The place of the hormone must be explore in selected intermediate risk treated by brachytherapy.
Molecular subtyping to predict better clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine with or without trastuzumab.
Authors: Stefan Gluck, Melanie Royce, Lisette Stork-Sloots, Femke De Snoo
Journal: Journal of Clinical Oncology (2013)

11090 Background: Classification into molecular subtypes is important for the selection of therapy for patients with early breast cancer. Here we determine rates of pathological complete response (pCR) in early stage breast cancer to neoadjuvant capecitabine plus docetaxel, +/- trastuzumab, and investigate MammaPrint together with the molecular subtyping profile BluePrint as markers of pathological response in comparison to other biomarkers. Methods: This analysis was carried out on data from 122 patients enrolled in a multicenter study (XeNA) of neoadjuvant therapy for four 21-day cycles with capecitabine 825 mg/m 2 plus docetaxel 75 mg/m 2 if HER2-, and a standard trastuzumab dose if HER2+ (Glück , BCRT 2011). Clinical and pathological features, TP53 mutation analysis and PAM50 results were collected through GEO at NCBI (GSE22358). MammaPrint and BluePrint outcomes were determined from the available gene expression data and resulted in 4 distinct molecular groups: Luminal A (MammaPrint Low Risk/Luminal-type), Luminal B (MammaPrint High Risk/ Luminal-type), Basal-type and HER2-type. Results: In patients who completed 4 cycles of chemotherapy and surgery the overall pCR rate was 16%. Stratified by BluePrint pCR was observed in 1/15 (7%) of the Luminal A and 2/44 (5%) of Luminal B, in 10/22 (45%) of the HER2-type and in 7/41 (17%) of the Basal-type. The response rate among TP53 mutated patients was 6/61 (26%), which was significantly higher than TP53 wild-type patients (3/54 4%; p=0.012). Concordance of BluePrint/MammaPrint with PAM50 molecular subtyping was 61%. Conclusions: Molecular Subtyping with BluePrint and MammaPrint can identify better outcomes of patients in the neo-adjuvant setting. Patients with Luminal A breast cancer have a good baseline prognosis with excellent survival and may not benefit from chemotherapy (Glück, SABCS 2013). MammaPrint and BluePrint provide predictive information for patients treated with treated with docetaxel-capecitabine +/- trastuzumab.
French national histological brain tumor registry.
Authors: Luc Bauchet, Valerie Rigau, Sonia Zouaoui, Amelie Darlix, Faiza Bessaoud, Fabienne Bauchet, Dominique Figarella-Branger, Pascale Fabbro-Peray, Brigitte Tretarre, Michel Fabbro, Marie Charissoux, Christine Kerr, Catherine Goze, Laurent Capelle, Hugues Duffau, Luc Taillandier, Helene Mathieu-Daude
Journal: Journal of Clinical Oncology (2015)

e13051 Background: National brain tumor registries exist only in few countries, and systematic brain tumor declaration is not mandatory in many countries. Here we propose an easy method to build a national registry for primary central nervous system tumor (PCNST) with histological validation, and we present the results at national level. Methods: The French Brain Tumor DataBase (in agreement and with the active participation of Scientific Societies involved in neuro-oncology in France) identified all newly diagnosed and histologically confirmed (according to the WHO classification) PCNST patients in metropolitan France (population in 2008: 62 134 866 inhabitants), since 2006 and prospectively collected initial data. For each patient, the neurosurgeon and the neuropathologist fill-out a simple datasheet containing socio-demographic, clinical, radiological and histopathological data. Moreover, in order to improve the exhaustiveness of data collection, an annual listing of all cases, analyzed by each neuropathology department, was collected. In some specific cases when data from the datasheet and the listing did not match, a clinical research technician contacted the neuropathology department directly in order to verify the data. Results: In 6 ys period (2006-2011) 57,816 cases of newly diagnosed PCNST were recorded (male/female 0.87, median age at diagnosis 56 ys, resection 79%, cryopreserved tumors 23.4%, gliomas 39.2%, tumors of the meninges 32.5%, tumors of cranial and paraspinal nerves 9.4%, all others 18.9%). Crude rate for all newly diagnosed PCNST with histological validation was 15.5 per 100,000. To enable international comparisons, standardized rates (per 100,000) were calculated as follows: 14.5 (population of reference: Europe), 14.1 (reference: USA), and 12.0 (reference: world). For all cases (nearly 140) histological type and subtype according to the 2007 WHO classification, number (Nb), standardized incidence rates, sex ratio, median age, Nb of cryopreserved tumors, Nb of biopsy/resection will be detailed in the presentation. Conclusions: The relevance of such national histological brain tumor registry is high for epidemiological, basic research and population studies.
OPTIMIS: An international observational study to assess the use of sorafenib after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).
Authors: Markus Peck-Radosavljevic, Jean-Luc Raoul, Han Chu Lee, Masatoshi Kudo, Keiko Nakajima, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2014)

TPS4155 Background: TACE is currently recommended for the treatment of patients with intermediate-stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage B). However, it remains unclear which patients are most likely to benefit from TACE, or when TACE should be stopped and alternative treatments considered. The multikinase inhibitor sorafenib is the only systemic therapy currently approved for the treatment of advanced HCC. The aim of this observational study is to prospectively collect data from patients with HCC who either receive or do not receive sorafenib subsequent to TACE. Methods: Patients are eligible if ≥18 years of age, have histologically/cytologically documented or radiographically diagnosed HCC classified as BCLC stage B or higher, have a life expectancy of ≥8 weeks, and a decision to treat with TACE has been made at the time of study enrollment (one prior TACE treatment is allowed if performed at the same center and all required data about the procedure are available). Treatment decisions made before a patient is enrolled, and during the observation period, must be according to investigators’ regular practice. Exclusion criteria include any systemic anti-cancer therapy prior to the first TACE, or participation in an interventional study of locoregional or systemic therapy. The primary objective is evaluation of overall survival in patients who received sorafenib subsequent to TACE non-eligibility (early sorafenib) compared with those who did not (non-early sorafenib). The non-early sorafenib group includes patients who did not receive sorafenib or received it at a later point. Secondary objectives include progression-free survival, time to progression, tumor response, and safety. Planned enrollment is approximately 1600 patients from about 30 countries across Europe, Latin America, and Asia-Pacific, and from Canada. One interim analysis is planned once 500 patients have been observed for at least 6 months. Final analysis will be performed once the last enrolled patient has been followed for 18 months, has been lost to follow-up, or has died. The study began in October 2013 and 69 patients have been enrolled as of January 2014. Clinical trial information: NCT01933945.
Association of EGFR mutations with ERCC1 expression in non-small cell lung cancer.
Authors: Wenhua Liang, Ziying Lin, Yutong Xu, Yaxiong Zhang, Jianxing He
Journal: Journal of Clinical Oncology (2015)

e19075 Background: Previously we presented some evidence that patients with EGFR mutations might be more sensitive to cytotoxic chemotherapies (namely platinum-based regimens) compared with wild type patients in advanced NSCLC. Thus, we sought to explore the underlying mechanism from the perspective of markers for chemotherapy sensitivity. Methods: Electronic database were searched for eligible studies. All common markers for chemosensitivity in NSCLC, including ERCC1, RRM1, TS, BRCA1, b-tubulin 3, were considered. EGFR mutations were limited to 19 exon deletion and L858R mutation in 21 exon. Results: Only ERCC1, BRCA1 and b-tubulin 3 could be analyzed with 10, 3 and 2 relevant studies respectively. In EGFR mutated patients, high ERCC1 expression was significantly less frequent compared with wild type patients (OR 0.66, 95% CI 0.47 to 0.91, P = 0.01; heterogeneity, I2= 1%). On the other hand, we did not observed significant difference in BRCA1 (OR 0.88, 95% CI 0.47 to 1.65, P = 0.68) and b-tubulin 3 (OR 0.80, 95% CI 0.35 to 1.85, P = 0.60) expression between EGFR mutated and wild type patients. Conclusions: We demonstrated through comprehensive analyses that EGFR mutations were negatively associated with ERCC1 expression. This might be an underlying reason why EGFR mutated patients were more sensitive to cytotoxic chemotherapies especially platinum-based regimens.
Germline DNA repair mutations in metastatic castration-resistant prostate cancer: Therapy response and applicability of circulating tumor DNA.
Authors: Werner J. Struss, Matti Annala, Evan W Warner, Kevin Beja, Gillian Vandekerkhove, Amanda Wong, Martin Gleave, Kim N. Chi, Alexander William Wyatt
Journal: Journal of Clinical Oncology (2017)

140 Background: Germline mutations in DNA repair genes were recently reported in 8-12% of patients with metastatic castration-resistant prostate cancer (mCRPC). It is unknown whether these mutations associate with differential response to Androgen Receptor (AR) targeted therapy. The aim of this study was to determine the clinical response of mCRPC patients with germline DNA repair defects to AR-directed therapies, and secondly to establish whether biallelic DNA-repair gene loss is detectable in matched circulating tumor DNA (ctDNA). Methods: We recruited 319 mCRPC patients and performed targeted germline sequencing of 22 DNA repair genes. In affected patients, matched plasma ctDNA was also sequenced. Prostate-specific antigen response and progression were assessed in relation to initial androgen deprivation therapy (ADT) and subsequent therapy for mCRPC using Kaplan-Meier analysis. Results: 24/319 (7.5%) patients had deleterious germline mutations, with BRCA2 (n = 16), PALB2 (n = 2) and CDK12 (n = 2) being the most frequent. Patients (n = 22) with mutations in genes linked to homologous recombination were heterogeneous at initial presentation but after starting ADT progressed to mCRPC with a median time of 12.3 months (95% CI 5.1-18.4). The median time to progression on first and second line AR-targeted therapy in the mCRPC setting was 3.2 months (95% CI 1.9-4.4) and 1.0 month (95% CI 0.8-1.1), respectively. For patients receiving chemotherapy as their initial therapy for mCRPC (n = 8) the median PFS was 7.5 months (95% CI 6.5-8.2). 10/11 evaluable patients with germline BRCA2 mutations had somatic deletion of the intact allele in ctDNA. Conclusions: mCRPC patients with germline DNA repair defects exhibit transient responses to AR-targeted therapy. Biallelic gene loss was robustly detected in ctDNA suggesting that this patient subset could be prioritized for therapies exploiting defective DNA repair using a liquid biopsy.
Outcomes of men who underwent treatment for prostate cancer from a prospective follow up of a racially diverse, multi-institutional active surveillance cohort.
Authors: Nora M. Haney, Allison H. Feibus, James Liu, Gabriel Leinwand, Elisa M. Ledet, Krishnarao Moparty, Brian E. Lewis, Raju Thomas, Oliver Sartor, Jonathan L. Silberstein
Journal: Journal of Clinical Oncology (2017)

e536 Background: Active surveillance (AS) is an increasingly accepted alternative to treatment for low-grade prostate cancer (PCa). However, it remains unclear what factors may predict which patients will upgrade to a higher grade cancer. We sought to analyze the characteristics at time of diagnosis and outcomes of those men in our racially diverse AS cohort who underwent treatment for PCa. Methods: Men from our AS database were analyzed. Inclusion criteria was PSA &lt; 20 ng/mL, Gleason Score ≤ 7, and clinical stage ≤ T2a. Men who elected active treatment for their PCa at diagnosis or refused subsequent imaging and biopsy were excluded from this cohort. Univariate analysis was done to compare the clinical variables of the treatment group with the entire cohort. Results: We identified 56 men who were treated for PCa from the 308 men currently enrolled in our AS cohort. All 56 men in the treatment group had low risk PCa at diagnosis and initiation of AS. At diagnosis, the treatment group was not significantly different in comparison with our entire cohort with respect to age, BMI, family history of PCa, PSA at diagnosis, prior negative biopsy, TRUS volume, PSAD, smoking status and clinical staging. However the eventual treatment group did differ at diagnosis with respect to greater linear length of cancer per core (p &lt; 0.01), greater % involvement of disease (p = 0.03), and greater number of total cores at time of diagnosis (p = 0.04). The men in this group underwent treatment for PCa for the following reasons: 36 for Gleason Score upgrading, 5 due to increased volume of disease, 6 due to rising PSA, 1 due to MRI findings, 1 due to rising PSA on Avodart and 7 elected treatment despite no significant changes in disease. 31 of the men had RARPs, 17 XRT, 4 had XRT + ADT, 3 had Brachytherapy, and 1 with XRT + salvage RP. Conclusions: Within our prospectively enrolled racially diverse AS cohort, the patients who underwent treatment for PCa had clinical factors that differed in comparison to the whole cohort. Further prospective study is needed to determine how these factors may ultimately impact long term outcomes.
Clinical impact of <i>EGFR</i> mutation fraction and tumor cellularity in <i>EGFR</i> mutation positive NSCLC.
Authors: Petra Martin, Carolyn Jane Shiau, Maria D Pasic, Ming Sound Tsao, Suzanne Kamel-Reid, Lisa Le, Brian Patrick Higgins, Susanna Y. Cheng, Ronald L. Burkes, Matilda Ng, Saroosh Arif, Tudor Roxana, Stephanie Chen Xing Lin, Peter Michael Ellis, Stacey Hubay, Sara Kuruvilla, Scott Andrew Laurie, Jing Li, Frances A. Shepherd, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2013)

e19077 Background: We investigated the impact of mutation fraction, tumour sample cellularity, and diagnostic specimen type on EGFR TKI response, time to treatment failure (TTF) and overall survival in advanced EGFR mutation positive NSCLC patients. Methods: From March 2010 to May 2012, EGFR testing in the province of Ontario (Canada) was conducted at a single centre, using fragment analysis for exon 19 deletion and Sau961 restriction enzyme digest for exon 21 mutation. Patients with EGFR mutation positive samples were identified, tumour cellularity, mutation fraction (percent tumour cells mutated) and clinical outcome data collected. Regression analysis was undertaken to assess the association between demographic variables, mutation fraction, tumour cellularity and sample type on clinical outcomes. Results: Of 173 patients identified to date, 153 received EGFR TKI and are included in this analysis, with median follow up of 10.6 months (range 0-44). Most are female (73%), never smokers (65%), have exon 19 deletions (55%; 45% exon21 L858R), and median age 64 years (range 34 to 95). Tumour specimens tested include resection (36%), cytology (32%), and core biopsy samples (32%). Median EGFR mutation fraction is 30% (range 1% to 96%); 18% had a low (&lt;10%) mutation fraction. Responses (any reduction) were seen in 66%, mixed response or stable disease in 28%, and progression in 7%. Median TTF of EGFR TKI therapy is 13.8 months. Median OS from TKI start is 24.1 months, with 1-, 2- and 3-year rates of 75%, 51% and 42%. In multivariable analysis, increasing mutation fraction was associated with EGFR TKI response (OR 2.5, p&lt;0.01), but not TTF or OS. Female sex was associated with TTF (HR 0.49, p=0.007), and testing of larger samples (lobectomy, wedge, excision) was associated with TTF and OS (HR 0.45, p=0.007; HR 0.26, p=0.0002). Exon 19 deletions are associated with a higher risk of death (HR 2.41, p=0.02) and a lower probability of response than L858R (OR 0.31, p=0.004). Conclusions: Pathologic features may be relevant to clinical outcomes in EGFR mutation positive NSCLC, including mutation fraction, sample cellularity, specimen tested and mutation type. Validation of the use of EGFR mutation fraction in clinical decision-making is ongoing.