tbuckley/cabot-search huggingface dataset:
Outcome of childhood T-cell acute lymphoblastic leukemia (T-ALL): Results from DFCI protocol 05-001.
Authors: Andrew E. Place, Kristen E. Stevenson, Marian H. Harris, Olga K. Weinberg, Lynda M. Vrooman, Sarah K. Hunt, Samia S. Ahmed, Uma H. Athale, Luis Antonio Clavell, Peter D. Cole, Kara M. Kelly, Caroline Laverdiere, Jean-Marie Leclerc, Bruno Michon, Marshall A. Schorin, Jennifer JG Welch, Barbara Asselin, Donna S. Neuberg, Stephen E. Sallan, Lewis B. Silverman
Journal: Journal of Clinical Oncology (2014)

10015 Background: T-ALL accounts for ~ 15% of pediatric ALL; in general, outcomes have been less favorable than those for B-ALL. Methods: Between 2005-11, 97 evaluable patients (pts) aged 1-18 years (yrs) with newly diagnosed T-ALL were enrolled on DFCI ALL Consortium Protocol 05-001. Early T-cell precursor (ETP) subtype was retrospectively assessed in 90 pts by flow cytometry. End-Induction minimal residual disease (MRD) was assessed by PCR. All 97 pts were initially treated as high-risk regardless of other presenting features; 2 pts were assigned more intensive post-induction therapy based on cytogenetics (MLL-R:1; BCR-ABL:1). Results: Presenting features and outcomes are shown in Table 1. The 4-yr EFS and OS for all T-ALL pts was 83% and 89%, respectively (median follow-up: 4.3 yrs). End-induction MRD was evaluable in 58 (67%) pts achieving CR; high MRD (>0.001) was associated with an inferior DFS (high MRD (N=15): 79%, low MRD (N=43): 95%, p=0.047). ETP subtype was identified in 16 pts (18%). ETP pts had a higher rate of induction failure (31% vs. 4%, p<0.01) and an inferior EFS (62% vs. 89%, p<0.01). None of the ETP pts who achieved CR after the 1st month of treatment subsequently relapsed. Conclusions: Overall outcome for T-ALL pts on Protocol 05-001 was favorable, especially for non-ETP pts with low MRD (4-yr DFS 98%; 95% CI:[84-99%]). Future studies should focus on intensifying post-induction treatment for pts with high end-induction MRD and modifying induction regimens for ETP pts. Clinical trial information: NCT00400946.Outcome and presenting features for T-ALL on DFCI 05-001. Total T-ALL N (%) non-ETP T-ALL N (%) ETP N (%) p-value* No. Pts. 97 74 16 Age <10 yrs 54 (56) 42 (57) 6 (38) 0.18 ≥10 yrs 43 (44) 32 (43) 10 (62) Median (range) yrs 8.5 (1.2, 17.9) 7.2 (1.2, 17.9) 12.1 (2.9, 17.9) 0.07 Sex, Male 71 (73) 55 (74) 10 (62) 0.37 WBC K/uL, median (range) 64.3 (0.9, 905.0) 81.1 (2.9, 905.0) 13.4 (1.8, 259.2) <0.01 Mediastinal mass present 43 (44) 37 (50) 3 (19) 0.03 4 yr EFS (%) [95% CI] 83 [74-90] 89 [79-94] 62 [35-81] <0.01 4 yr DFS [95% CI] 93 [85-97] 94 [85-98] 100 [NA] 0.46 4 yr OS (%) [95% CI] 89 [80-94] 92 [83-97] 81 [51-93] 0.09 Induction failure 8 (8) 3 (4) 5 (31) <0.01 Induction death 2 (2) 1 (1) 1 (6) 0.33 Achieved CR 87 (90) 70 (95) 10 (62) <0.01 * Non-ETP T-ALL vs ETP; Pts achieving a CR.
Postoperative nomogram for predicting survival after resection for intrahepatic cholangiocarcinoma.
Authors: Dario Ribero, Stefano Rosso, Antonio Daniele Pinna, Gennaro Nuzzo, Alfredo Guglielmi, Luca Aldrighetti, Francesco Leone, Massimo Aglietta, Stefano Maria Giulini, Giorgio Enrico Gerunda, Mariano Tomatis, Pasquale Berloco, Fulvio Calise, Enrico Opocher, Salvatore Gruttadauria, Guido Torzilli, Lorenzo Capussotti
Journal: Journal of Clinical Oncology (2013)

4129 Background: Conventional staging systems have limited value for survival estimation in individual patients because of the multiple predictors of outcome. Nomograms may overcome these limitations. Thus we developed and internally validated a postoperative nomogram to predict survival after resection of intrahepatic cholangiocarcinoma (IHC) and compared its predictions to those obtained using the 7 th Ed. AJCC/UICC stage groupings. Methods: Prospective clinicopathologic data from 574 patients who underwent hepatic resection at 12 tertiary hepatobiliary centres (1995-2011) were used. After inputting missing values with regression imputation, the nomogram was developed from a Cox regression model with overall survival (OS) as the primary end-point. Calibration and internal validation were performed calculating the agreement between observed and predicted outcomes in terms of percentage of predicted errors (PE). Discrimination was quantified with the concordance index (CI). Both CI and PE were then corrected for over-optimism using bootstrapping with 100-fold cross-validation sampling. Credibility intervals around 3- and 5-year predicted survival were estimated from an empirical Bayesian model. Results: At last follow-up (median duration 27.6 months) 243 patients had died. Three and five-years OS were 52% and 39%. The predictive accuracy of the nomogram (CI: 66.5), which includes 7 variables (tumour size and number, lymph-node metastases, vascular invasion, perineural invasion, CA19.9 level, and radicality of resection), was good and superior to that of the current AJCC/UICC staging system (CI: 58.4). Percentage of PE for the AJCC/UICC staging system were 24%, while the studied model offered a PE slightly under 20%. Heterogeneity was observed in the distribution of nomogram-predicted survival probabilities within stage groups. Conclusions: The nomogram developed in this study overcomes some of the prognostic limitations associated with simple models by including all prognostic variables excluded from the AJCC/UICC staging system and may serve as an instrument for future refinements in determining individual patient prognosis necessary for accurate patients stratification.
Pilot study of secondary causes of osteoporosis/osteopenia in adults with breast cancer.
Authors: Tomoko Tagawa, Arti Hurria, Joanne E. Mortimer, Azar Khosravi, Behrouz Salehian, George Somlo, Thehang H. Luu, Tao Feng, Laura Zavala
Journal: Journal of Clinical Oncology (2014)

e20587 Background: Osteoporosis is a concern for older adults diagnosed with breast cancer (BC) due to treatment induced bone loss. There is limited data on the prevalence of 2ndary causes of osteoporosis (conditions other than aging and menopause) among women with BC. However, failure to diagnose and treat 2ndary causes may lead to failure of osteoporotic therapy. Purpose: Our hypothesis is that 2ndary causes of bone loss are prevalent in women with newly diagnosed non-metastatic breast cancer (NMBC) with new osteopenia/osteoporosis. The goal of this study is to describe the prevalence of 2ndary causes of bone loss in women with treatment naive NMBC and osteopenia/osteoporosis. Methods: We prospectively followed 48 consecutive women with new NMBC, who are being evaluated for adjuvant chemotherapy and/or hormone therapy and who have been referred to endocrinology clinic for evaluation of new osteopenia/osteoporosis. We calculated the 10-year probability of major osteoporotic fracture using the FRAX score and estimated the prevalence of 2ndary causes of bone loss (lifestyle, medication, metabolic, endocrine, and other medical etiology). Results: The mean age of the cohort is 63.9 (STD=9.0). Nearly 90% of the women have stage I or II BC. 87.5% of the women have hormone receptor positive BC. The ethnicity is 34 whites, 9 asians, 2 blacks, and 3 others. The mean 10-year probability of major osteoporotic fracture is 9.3% (13/48 have >10% to 20% and 3/48 have >20% 10-year probability of major osteoporotic fracture). Conclusions: This pilot study suggests a high prevalence of 2ndary causes of bone loss, including 2 or more 2ndary causes, among women with new diagnosis of NMBC and osteopenia/osteoporosis. These women may benefit from standardized evaluation of 2ndary causes of bone loss to optimize their bone health. Clinical trial information: NCT01277562. Prevalence of secondary causes of bone loss n=48 (8 osteoporosis, 40 osteopenia) Lifestyle Heavy alcohol 4 Tobacco 4 Low dietary calcium 2 Medication/surgery Glucocorticoid excess 2 Gastric banding 1 Endocrine Vit D deficiency (25 OH Vit D <30ng/mL) 27 Vit D deficiency + ↑ PTH 4 Primary ↑ PTH 3 Hypercalciuria 2 Hyperthyroidism 2 Prevalence of secondary causes of bone loss Overall 68.80% 1 cause 41.70% ≥2 causes 27.10%
Pharmacogenetic pathway analysis of irinotecan
Authors: G. L. Rosner, J. C. Panetta, L. Xiao, F. Innocenti, M. J. Ratain
Journal: Journal of Clinical Oncology (2006)

3073 Background: Irinotecan (IRN), a chemotherapeutic agent for various solid tumors, is the parent compound for SN-38, the active metabolite. The pharmacokinetics (PK) of IRN are complex and associated with variability in clinical outcomes. We sought to learn about the pharmacogenetics (PGx) of IRN by relating the drug’s PK to polymorphisms (SNPs) in drug-metabolizing enzyme and transporter genes potentially relevant to IRN. Methods: We measured concentrations of IRN and 3 metabolites in 86 patients. We fit a novel 7-compartment (15 parameter) model (including enterohepatic circulation) to the concentration data for IRN and metabolites. We applied principal components (PCs) analysis to the patient-specific PK model parameters to reduce the number of outcome variables and to identify appropriate linear combinations of the parameters that relate to IRN’s metabolic pathways. We then analyzed associations between SNPs and PCs to learn about functional polymorphisms. Associations are significant if p &lt; 0.05. Results: We found that 8 PCs accounted for 90% of the total variation in the 15 fitted parameters. PC #1 corresponded to SN-38 in plasma and was associated with SNPs in the CYP3A4, MRP2, and ABCG2 genes. PC #2, the IRN compartments’ PC, was associated with a SNP in OATP-C*1b. The APC PC was associated with a CYP3A5 SNP. The SN-38 glucuronidation PC was associated with UGT1A1 and UGT1A9 polymorphisms. Conclusions: PC analysis is a useful way to reduce the dimension of multiple PK parameters and to produce pathway-specific and interpretable measures relating to PK. The use of PCs in PGx analysis allows identification of potential functional polymorphisms, which can be further evaluated in other data sets. [Table: see text]
Extended vs. limited laparoscopic pelvic lymph node dissection for prostate cancer: The value of Partin tables in selection of the need for and the extent of dissection
Authors: K. Touijer, F. Rabbani, J. Romero Otero, F. Secin, B. Guillonneau
Journal: Journal of Clinical Oncology (2006)

4654 Background: To determine if pelvic lymph node dissection (LND) can be omitted in prostate cancer patients at low risk of nodal metastases according to the Partin tables and to determine the yield on extended vs limited LND in patients at high risk to better define the appropriate template of dissection. Methods: A total of 577 patients with clinically localized prostate cancer underwent a laparoscopic radical prostatectomy (LRP). In the first 363 patients, a cutoff of 1% on the Partin tables’ predicted probability of lymph node invasion (PPLNI) was used to select patients for a limited LND (external iliac nodes only). In the subsequent 214 patients, all patients underwent an extended LND (external iliac, obturator and hypogastric nodes). Patients were classified into 4 groups: Group I, 186 patients with a PPLNI ≤1%, did not undergo a LND; Group II, 110 patients with PPLNI ≤ 1%, underwent an extended LND; Group III, 177 patients with PPLNI &gt;1% underwent a limited LND and Group IV, 104 patients with PPLNI &gt;1%, underwent an extended LND. We compared Group I and II to assess the value of the Partin tables in selecting low risk patients for nodal metastasis. Multivariate logistic regression analysis was performed to compare the node positivity rate between groups III and IV, controlling for preoperative and pathological parameters. Results: None of the patients in group II had a positive lymph node after an extended LND. On multivariate analysis, controlling for PSA, biopsy Gleason, clinical stage, pathological Gleason and stage, and seminal vesicle invasion, the extended LND independently impacted the rate of node positivity with a relative risk (RR) of 15.6 (95% CI 3.7 -66.4, p &lt; 0.001). The median (mean) number of nodes retrieved was 9 (10) and 14 (15) after limited and extended LND respectively (p &lt; 0.001). Conclusions: A lymph node dissection including the external iliac, obturator and hypogastric lymph node groups yields positive nodes more frequently and retrieves a higher total nodal count than the often-performed LND limited to the external iliac nodes. Decision to forgo LND in low risk patients needs to be validated by long-term biochemical recurrence data No significant financial relationships to disclose.
The relations between age and androgen deprivation therapy use among men receiving radiation therapy for prostate cancer in the Medicare population.
Authors: Jennifer L. Quon, James B. Yu, Pamela R. Soulos, Cary P. Gross
Journal: Journal of Clinical Oncology (2012)

e15150 Background: For older men with prostate cancer who are undergoing radiotherapy, the benefit of neoadjuvant and concurrent androgen deprivation therapy (ncADT) varies according to tumor characteristics and life expectancy (LE). National Comprehensive Cancer Network (NCCN) guidelines recommend ncADT for men with high-risk cancer characteristics, but not for men with low-risk cancer, or for men with LE &lt; 5 years. Although older patients with shorter LE have the lowest likelihood of benefit, it is unclear whether ncADT is used less frequently in this group. Methods: We used the Surveillance, Epidemiology, and End Results-Medicare database to assess patterns of ncADT use among men diagnosed with prostate cancer during 2004 through 2007 who received external beam radiation. Men were stratified according to NCCN guidelines into low- (T1-T2a/N0/M0 and Gleason 2-6 and PSA&lt; 10 ng/mL), intermediate- (T2b-T2c or Gleason 7 or PSA 10-20 ng/mL), and high- (Gleason &gt;7 or PSA&gt; 20 ng/mL) risk groups. Men were further stratified according to LE, which was calculated based on age and comorbid illness. We used logistic regression to identify patient and clinical factors associated with ncADT use within each risk group. Results: There were 11,080 men in the sample (mean age= 74.2 years; 83.5% white). The use of ncADT was highest in the high-risk group (80.7%). However, a considerable number of men in the intermediate- (54.1%) and low-risk (27.8%) groups also received ncADT. Compared to men with longer LE, men with LE &lt; 5 years had higher rates of ncADT use in all risk groups. For instance, in the low-risk group 32.7% men with LE &lt; 5 years received ncADT compared to 26.5% men with LE ≥ 10 years. Similarly, within each risk group, advancing age was associated with a higher likelihood of receiving ncADT (OR for men aged 80-84 compared to 67-69 = 1.93(95% CI 1.37-2.70); 1.51(95% CI 1.22-1.87); and 1.71, (95% CI 1.14-2.57) for high-, intermediate-, and low-risk groups, respectively). Conclusions: The use of ncADT in actual practice is not consistent with guideline recommendations and is used more frequently among men who are older, have a shorter LE, and are less likely to benefit from therapy.
Predictors of response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer.
Authors: Halle C. F. Moore, Baidehi Maiti, Lisa A. Rybicki, Christine Booth, Jame Abraham, G. Thomas Budd, Steven Ware Andresen, Erinn Downs-Kelly
Journal: Journal of Clinical Oncology (2015)

e11506 Background: Genomic assays are routinely used for risk assessment and for prediction of response to adjuvant chemotherapy for ER-positive breast cancer. While the Mammostrat assay (Clarient, Aliso Viejo, CA ) provides prognostic information, its performance in predicting response to chemotherapy is unknown. We sought to evaluate predictors of response to neoadjuvant chemotherapy for ER-positive breast cancer. Methods: We identified a cohort of patients with ER-positive operable breast cancer treated with neoadjuvant chemotherapy at the Cleveland Clinic who had both core biopsy and surgical pathology specimens available. Mammostrat testing was performed on core biopsy specimens for a subset of these patients. Patient and tumor characteristics as well as treatment information was collected. Residual Cancer Burden (RCB) was evaluated in post-treatment surgical specimens. Pathologic complete response (pCR) rates and RCB values were compared amongst categories of age, race, menopausal status, HER2 status, tumor grade, stage, chemotherapy regimen and Mammostrat risk category. Associations with pCR were analyzed with Cochran-Armitage or Fisher’s exact test. Associations with RCB were analyzed with Jonckheere-Terpstra, Cochran-Armitage, or Cochran-Mantel-Haenszel correlation test. Results: Among 91 ER-positive patients treated with neoadjuvant chemotherapy, 5 had pCR. No pCRs were observed in the 29 who had Mammostrat testing. Only HER2 positivity (p = 0.05) and higher nuclear grade (p = 0.041) were associated with pCR. Greater RCB was associated with HER2 negativity (p = 0.002), lower nuclear grade (p = 0.042) and higher stage (p = 0.017). Mammostrat results did not correlate with RCB. Conclusions: Greater RCB following neoadjuvant chemotherapy for ER-positive breast cancer was associated with HER2 negativity, lower nuclear grade and higher clinical stage; pCR occurred only in high grade tumors and was more likely in HER2-positive disease. Mammostrat results were not predictive of chemotherapy benefit in the subset tested.
Sequencing in metastatic castration-resistant prostate cancer (mCRPC): Updated results of the FLAC International Database.
Authors: Nicolas Delanoy, Antoine Angelergues, Eleni Efstathiou, Revekka Gyftaki, Piotr Jan Wysocki, Nuria Lainez, Iria Gonzalez, Daniel E. Castellano, Mustafa Ozguroglu, Iciar Garcia Carbonero, Aude Flechon, Pablo Borrega, Aline Guillot, Begona Campos Balea, Sylvestre Le Moulec, Emilio Esteban, Javier Munarriz, Claire Barker, Alison J. Birtle, Stephane Oudard
Journal: Journal of Clinical Oncology (2017)

267 Background: Optimal sequencing of new androgen-receptor targeted agents (ART) abiraterone and enzalutamide with docetaxel (DOC) and cabazitaxel (CABA) is unknown. In this large retrospective cohort of mCRPC patients (pts) treated with CABA after docetaxel (DOC), we evaluated the impact of 3 different sequences: DOC → CABA (group 1, n = 267) Or DOC → ART → CABA (group 2, n = 183) Or DOC → CABA → ART (group 3, n = 124). Methods: Records of 574 consecutive mCRPC patients were retrospectively collected in 44 centres in 6 European countries (France, Spain, UK, Greece, Poland, Turkey) from August 2012 to July 2016. Disease history and clinical characteristics at initiation of DOC therapy and outcomes were collected. Factors influencing OS were evaluated using multivariate stepwise logistic regression. Results: At DOC initiation, median age was 67 years, 83% of pts were ECOG 0-1, 45.1% had pain and 10.8% had visceral metastases. Median number of DOC cycles was 7 (6 in group 2, 7 in groups 1 and 3). Median number of CABA cycles was 6 (6 in groups 1 and 2, 7 in group 3). Median duration of ART treatment was 5.9 and 4.4 mths in groups 2 and 3, retrospectively. Median OS from first DOC cycle were 30.1, 37.1 and 40.1 mths in groups 1, 2 and 3, respectively. Factors influencing OS are summarized in the table below. Conclusions: Results of this retrospective cohort suggest that patients receiving DOC → CAB → ART show the greatest OS. High baseline PSA, short response to first-ADT and clinical progression of pts are major prognostic factors of OS at DOC initiation. The window of opportunity for chemotherapy should not be missed. [Table: see text]
Changes in multiparametric prostate MRI and immune subsets in patients (Pts) receiving neoadjuvant immunotherapy and androgen deprivation therapy (ADT) prior to radiation.
Authors: Ravi Amrit Madan, Baris Turkbey, Lauren Marissa Lepone, Renee Nicole Donahue, Italia Grenga, Samuel Borofsky, Peter A. Pinto, Deborah E. Citrin, Aradhana Kaushal, Andra V. Krauze, Sheri McMahon, Myrna Rauchhorst, Anna Couvillon, Martin H. Falk, Peter Eggleton, Peter L. Choyke, William L. Dahut, Jeffrey Schlom, James Gulley
Journal: Journal of Clinical Oncology (2017)

30 Background: Endorectal(er) MRI is an emerging tool in assessing intraprostatic tumors. Immunotherapy development in prostate cancer has been limited due to the lack of intermediate (bio)markers of response. Methods: Untreatedpts with high-risk prostate cancer were randomized in a trial (NCT01496131) of standard ADT+Radiation + an immunotherapy targeting MUC1 (tecemotide, aka L-BLP25). Pts had erMRI at baseline and after 2 months of ADT+/- biweekly immunotherapy. Low dose (300 mg/m 2 , maximum 600 mg) cyclophosphamide for regulatory T-cell depletion preceded first immunotherapy. Multiparametric MRI included evaluation of apparent diffusion coefficient (ADC) maps from diffusion-weighted MRI. Monthly peripheral blood assessments utilized flow cytometry to evaluate immune cell subsets. This analysis focuses on the 2 month neoadjuvant period of ADT+/-immunotherapy before radiation. Results: 28 pts (n = 14/arm) with high risk prostate cancer (Gleason 8-10, PSA &gt; 20, or stage T3) were enrolled. PSA declined in all pts 2 months after ADT. erMRI findings at 2 months indicated greater improvements in ADC values in pts receiving immunotherapy+ADT vs. ADT alone. Improved ADC on MRI suggests improvements in intratumoral diffusion and has been associated with decreased tumor density. This relative improvement between the groups occurred both per patient (p = 0.16) and per lesion (p = 0.031). Relative to baseline, pts receiving immunotherapy+ADT had increases in CTLA4 + CD8 + T-cells consistent with immune activation (p = 0.0134) and decreases in myeloid derived suppressor cells (MDSCs; p = 0.0353) during the neoadjuvant period corresponding to the erMRI changes. These immune findings were not seen in the ADT alone group. Conclusions: Pts who received immunotherapy+ADT for 2 months had greater improvements in ADC values on erMRI, consistent with decreased tumor density, relative to pts receiving ADT alone. Corresponding increases in activated CD8 + T-cells and decreases in MDSCs were seen in pts receiving vaccine+ADT. These preliminary findings suggest that ADC on MRI may be useful in assessing immunologic impact. Further study is warranted. Clinical trial information: NCT01496131.