tbuckley/cabot-search huggingface dataset:
LUX-H&amp;N 1: A phase III, randomized trial of afatinib versus methotrexate (MTX) in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based therapy.
Authors: Jean-Pascal H. Machiels, Lisa F. Licitra, Robert I. Haddad, Makoto Tahara, Liz Svensson, Xiuyu Julie Cong, Eva Ehrnrooth, Ezra E. W. Cohen
Journal: Journal of Clinical Oncology (2012)

TPS5598 Background: EGFR (ErbB1) is expressed in 90% of HNSCC and associated with poor prognosis. Despite clinical benefit (CB) of EGFR-targeted treatments such as cetuximab treatment resistance will occur resulting in a need for novel targeted treatments to improve prognosis. Afatinib is an ErbB Family Blocker that irreversibly blocks signaling from all relevant ErbB Family dimers and may overcome limitations of current EGFR-targeted treatments in HNSCC. In a randomized, proof-of-concept, Phase II trial, afatinib demonstrated comparable anti-tumor activity to cetuximab in pts with R/M HNSCC progressing after platinum-based therapy (Seiwert TY, et al; THNO, November 2011; Abs 40). Methods: LUX-H&amp;N 1 is a phase III, randomized, open-label trial (NCT01345682) evaluating efficacy and safety of afatinib vs. MTX in pts with R/M HNSCC who have progressed after platinum-based therapy. Key eligibility criteria: confirmed R/M HNSCC not amenable to salvage surgery/radiotherapy; documented PD after cisplatin and/or carboplatin for R/M disease; any other than 1 previous platinum-based regimen for R/M disease; ECOG status 0 or 1; no PD ≤3 months of completion of curatively intended treatment for locoregionally advanced or metastatic HNSCC; and no prior EGFR-targeted small molecules treatment. Eligible pts are stratified into four strata: ECOG performance score (0 vs. 1) and prior use of EGFR-targeted antibody therapy (Yes/No) given in the R/M setting. Pts are randomized 2:1 to: afatinib (40mg/d orally) or MTX (40mg/m 2 IV weekly). Dose changes are permitted according to absence/presence of drug-related AEs (afatinib: escalation to 50mg/d and/or reduction to 40, 30 then 20mg/d; MTX: escalation to 50mg/m 2 and/or reduction to 40, 30 then 20mg/m 2 ). Pts receive continuous treatment until PD or AEs requiring withdrawal. Randomized treatment may continue beyond PD in case of CB as judged by the investigator. The primary endpoint is PFS and secondary endpoints include OS, OR, health-related QOL and safety. Target enrolment is 474 pts and completion of pt recruitment and data analyses are awaited.
Psychosocial outcomes of siblings of pediatric stem cell transplant survivors.
Authors: David Kyle Buchbinder, Sunita K. Patel, Jacqueline N. Casillas, Diane Nugent, Steven Neudorf, Leonard S. Sender, Lilibeth Ramilo Torno, Heather Huszti, Lonnie K. Zeltzer, Susan Kenyon Parsons
Journal: Journal of Clinical Oncology (2014)

9528 Background: In addition to associated morbidity and mortality of hematopoietic stem cell transplantation (HSCT) for the recipient, one of the consequences is the impact of the HSCT experience on the family. Our aim was to describe the psychosocial health of siblings of HSCT survivors and to identify factors with adverse psychosocial health. Methods: A multi-institutional cross-sectional study design was utilized to assess parent-reported sibling psychosocial health, as measured by the Short Form (SF)-10 Health Survey for Children and the Pediatric Symptom Checklist 17 (PSC-17). Parent physical / emotional health was assessed using the SF-12. Family impact was assessed using the Impact on Family Scale. HSCT and demographic data were collected. Summary statistics were calculated and compared to norms. Associations between sibling psychosocial health and parent physical / emotional health as well as family impact were assessed using correlations and regression. Results: Eighty-nine siblings (53% males) with a mean age of 11.2 years (range 4-14) representing HSCT survivors post-HSCT (mean 5.2 years, range 1-14), with malignant (73%) and non-malignant (27%) disorders were assessed. SF-10 psychosocial (mean 49.88, sd 10.90, p=0.92) and physical (mean 51.55, sd 8.59, p=0.10) health scores were not different from normative data. Behavioral / emotional problems (PSC-17 total score > 15) were noted in 24% of siblings. Parents demonstrated greater physical (mean 52.91, sd 8.29, p=0.002) and diminished mental (mean 45.89, sd 10.57, p<0.001) health compared to norms. Factors associated with adverse sibling psychosocial health included adverse parent physical / emotional health (p=0.003 and p<0.0001), and greater family impact (p<0.05). Factors associated with greater sibling behavioral / emotional problems included adverse parental emotional health (p =0.006). Conclusions: Siblings of HSCT survivors demonstrate positive outcomes overall; however, behavioral / emotional problems are evident. These concerns are associated with parental emotional health. The impact of HSCT on siblings and parents remains beyond the initial HSCT period. Psychosocial care for HSCT families should be extended for selected siblings and parents.
Surgery for NSCLC stages T1-3N2M0 having preoperative pathologically verified N2 involvement: A prospective randomized multinational phase III trial by the Nordic Thoracic Oncology Group.
Authors: Jens Benn Sorensen, Jesper Ravn, Han Kristian Pilegaard, Torben Palshof, Stein Sundstrom, Bengt Bergman, Jan Nyrop Jakobsen, Ulf Aasebø, Olfred Hansen, Peter Meldgaard, Bente Thornfeldt Soerensen, Erik Jakobsen, Per Jonsson, Marianne Ryberg, Jarmo Salo, Rune Haverstad, Henrik Riska
Journal: Journal of Clinical Oncology (2013)

7504 Background: Surgery is not generally considered standard of care in preoperative pathological verified spread to N2 mediastinal lymph nodes in NSCLC. Methods: Previously untreated histologically verified NSCLC stages T1-3N2M0 were randomized to reg. A (Paclitaxel 225 mg/m2 + Carboplatin AUC6 day 1 q 3 wks for 3 courses, followed by surgery with ipsilateral mediastinal lymph node sampling followed by radiotherapy 2Gy x 30 fractions, 5F/W) or reg. B: same as A without surgery (sequential chemo-radiotherapy). 406 pts were needed to detect a 10% 5-year survival increase with 80% power and type 1-error of 5%. The study was approved by ethical committees. Pts gave informed consent. Results: 170 pts were randomized to A and 171 to B from 1998-2009 when study closed due to concomitant chemo-radiotherapy becoming standard instead of sequential treatment. Median age was 61 years (range 33-76 yrs), 59% were males, 43% had performance status 0. Stages T1N2M0, T2N2M0, and T3N2M0 occurred in 19%, 60%, and 21%, respectively. Adenocarcinoma (ADC) and squamous cell carcinoma occurred in 50% and 29%, respectively. In reg. A, surgery was possible in 132 out of 170 pts (78%), 121 pts (71%) had complete resection while 11 pts (6%) had incomplete resection. Pathological-surgical stage pT0 occurred in 4%. Median progression free survival (PFS), OS and 5-years survival rate were 10 mths, 17 mths, and 20% for A (+ surgery) compared to 8 mths (p=0.144), 15 mths (p=0.172), and 16% (p=0.310) for B, respectively. ADC pts had better OS in A than in B (HR 0.60; p=0.002), and 5-year survivals 20% and 7% (p=0.017) respectively. Stage T1N2 had better OS in A than in B (HR 0.47; p=0.010), 5-year survivals 36% and 17%. Conclusions: There were no statistical overall significant advantage for surgery in addition to chemo-radiotherapy (A) compared to chemo-radiotherapy alone (B) but ADC pts and pts with T1N2 had significantly improved OS and 5-year survival rates in the surgery arm. Current standard treatment for T1-3N2M0 NSCLC is concomitant chemo-radiotherapy which was not used in this study, hence conclusions should be further tested with use of such treatment as reference arm.
Efficacy analysis of a phase III study of androgen deprivation therapy (ADT) +/- docetaxel (D) for men with biochemical relapse (BCR) after prostatectomy.
Authors: Michael J. Morris, Patrick Hilden, Martin Edwin Gleave, Andrew J. Armstrong, Michael Anthony Carducci, Fred Saad, Erica Simone Dayan, Julie Filipenko, Ilyse Acosta, Glenn Heller, Howard I. Scher
Journal: Journal of Clinical Oncology (2015)

5011 Background: The optimal treatment (tx) of men with castration sensitive prostate cancer (CSPC) who biochemically recur following a radical prostatectomy (RRP) is not known. Data from E3805 suggest that men with metastatic CSPC live longer if they receive D in addition to ADT relative to ADT alone. We tested this hypothesis in non-metastatic CSPC, via a phase III study (TAX3503). Methods: PC pts who underwent an RRP with BCR and a doubling time ≤ 9 months (mo) were eligible. PSA ≥ 1 ng/mL and testosterone ≥100 ng/dl were required. Randomization was 1:1 to receive leuprolide 22.5 mg q3 mo x 18 mo, bicalutamide 50 mg x 30 days, with D at 75 mg/m2 q3 weeks x 10 cycles (Arm A) or without D (Arm B). The primary endpoint was PFS defined as a detectable PSA or death. Pts with T recovery >50 ng/dl were evaluable. The intent to treat population (ITT) was also examined. A sample size of 412, to yield 370 evaluable pts, was calculated to detect a HR of 1.6 with 90% power. The trial was closed by the sponsor after the pts completed treatment; remaining pts were then followed to PFS via a registry for 18 mo’s. A test to detect a difference in the hazard rates between arms was generated by the log rank statistic. Results: 413 pts were randomized. Median f/u time in the ITT population was 31.5 mo’s (0.0-60.2). Data are summarized below in the Table. Conclusions: The clinical benefit of ADT + D relative to ADT alone in men with high-risk BCR after RRP appears to be marginal, although there is a statistical trend towards improved PFS. Data are limited by the biases intrinsic to post-protocol registries and by short duration of follow up, although tracking of pts continues. Clinical trial information: NCT01813370. Population Arm N Events Median PFS (95% CI) 1yr PFS prob 2yr PFS prob 3yr PFS prob HR (A vs. B) All randomized A 207 138 25.6 (25.0,27.8) 0.952 (0.910,0.975) 0.593 (0.514,0.663) 0.189 (0.130,0.257) 1.270 (1.006,1.603) P=0.044 B 206 148 23.1 (22.6,25.0) 0.960 (0.921,0.980) 0.472 (0.396,0.544) 0.104 (0.059,0.165) T-recovered A 129 106 26.5 (25.3,28.1) 0.961 (0.909,0.984) 0.641 (0.552,0.718) 0.202 (0.133,0.280) 1.285 (0.980,1.683) P=0.070 B 130 107 24.8 (22.9,25.3) 0.992 (0.947,0.999) 0.527 (0.437,0.609) 0.115 (0.060,0.188)
Intraarterial high-dose cisplatinum (IAHDP) as a part of the treatment of relapsed or locally advanced tumors of the head and neck (H&amp;N): A feasibility study.
Authors: Manuel Sureda Gonzalez, Antonio Moreno, Joseba Rebollo, A. Brugarolas, Rosa Cañon, Ignacio Azinovic, Aurora Crespo
Journal: Journal of Clinical Oncology (2012)

e16000 Background: IAHDP has been employed as a part of the treatment of relapsed or locally advanced H&amp;N tumors with controversial results (RADPLAT protocol). We hypothesize that patients (pts) with relapsed or locally advanced tumors in several locations can be treated with IAHDP, in order to achieve a response, to be followed by a consolidation with radiotherapy, surgery or both. Methods: Pts with relapsed or locally advanced tumors of the H&amp;N were treated with IAHDP (150 mg/m 2 /wk), after an initial supraselective angiography performed with the goal of mapping adequately the arterial supply. Prevention of toxicity with hyperhydration and simultaneous and delayed thiosulfate was done according to the previous schema of the RADPLAT protocol. Results: From June 2007 to September 2011, 11 patients – 8 M/ 3F; age 37-77 y, median 56 y- were treated (10 H&amp;N epidermoid carcinomas, 1 orbitary mts of adenocarcinoma of unknown origin). A total of 50 cycles were administered (2-9 per pt, median 4). In 4 pts IAHDP was part of the primary treatment; 7 pts were treated in relapse. Three pts were retreated after relapse, one of them two times. Five pts received radiotherapy simultaneously with IAHDP. Toxicity was generally mild and reversible. Mucositis g4 was observed in 3 cycles, facial edema requiring extra dexametasone in 7, pain during infusion in 9, nausea and vomiting in 3, lasting ipsilateral hypoacusia in 1, persistent trismus in 1. No significant alterations of renal function were observed. One pt progressed after the first cycle; 7 pts presented partial response (duration 1-6 m, median 2 m; 2 of them were converted to a complete response with surgery); 2 pts presented complete response with IAHDP simultaneous to radiotherapy. Four pts remained with no evidence of disease at 3+, 15+, 16+ and 38+ m respectively. Conclusions: IAHDP constitutes a feasible and promising therapeutic option for selected pts and a consolidation with surgery and/or radiotherapy after IAHDP is possible. Further development of this approach is warranted.
Predictors for malignant tissue (MT) in residual masses (RM) of non-seminomatous germ cell tumors (NSGCT) treated by chemotherapy (CT) before surgery.
Authors: Natacha Stern, Emmanuelle Bompas, Emilie Bogart, Fredrik Laestadius, Guillaume Mouillet, Friederike Schlurmann, Eric Leblanc, Nicolas Penel, Jean-Pierre Lotz, Eric Amela
Journal: Journal of Clinical Oncology (2017)

405 Background: About half of the patients operated for RM after CT for a NSGCT doesn’t benefit from surgery because RM contain only necrosis. We develop and validate a predictive score for identifying MT (teratoma and/or viable cancer cells) after primary CT for disseminated NSGCT. Methods: We have conducted a retrospective study. The development cohort (cohort 1) consists in 193 pts treated with CT and surgery of RM at the Oscar Lambret Cancer Center between 1997 and 2014. The validation cohort (cohort 2) consists in 98 pts treated in 5 other French sites. Size of RM, modification in size after CT, pre- and post-CT AFP levels, pre- and post-CT HCG levels, pre- and post-CT LDH levels were collected. The predictive factors have been first identified using univariate logistic regression analysis and then selected using step-by-step (forward) logistic regression. Discrimination has been assessed using Akaike Information Criterion (AIC) and ROC curve. Results: The rates of MT in the RM were 52% and 68%, in the cohort 1 and 2, respectively. The 1-, 2- and 5-y OS in the development cohort were 99, 97 and 95%, respectively. The 1-, 2 and 5-y relapse-free survival in the development cohort were 96, 92 and 91%, respectively. In univariate analysis, the predictive factors for MT were: size of RM &gt; 15 mm (OR=3.32 [95%-CI: 1.6-6.2], p=0.001), stable RM versus diminution in size of RM (OR=3.0 [1.5-5.9] p=0.001) or increase in size versus diminution in size of RM (OR=8.6 [1.7-41.9] p=0.008) and pre-CT AFP level &gt; ULN (OR=2.9 [1.4-6.3], p=0.006). The multivariate analysis had retained 2 predictors for MT: size of RM and pre-CT AFP level &gt; ULN. The ROC was 0.71 [0.61-0.80] with an AIC=143 in the development cohort, and was 0.59 [IC95% 0.46-0.72] in the validation cohort. The model showed adequate calibration with a Hosmer-Lemeshow test p=0.69. Conclusions: Surgery of RM is part of standard of care of disseminated NSGCT. However, this surgery is morbid and at the end about 50% of pts are free of MT. We have developed and validated a predictive score for identifying pts benefiting of surgery.
Sofosbuvir-based all-oral regimens for patients with chronic hepatitis C genotype 2 infection: integrated analysis of eleven clinical studies
Authors: S. Zeuzem, K.-H. Han, S.-H. Ahn, Y.-S. Lim, J.-H. Kao, W.-L. Chuang, M. Omata, F. Abramov, G. Crans, J. Llewellyn, M. Natha, S. De-Oertel, D. Brainard, G.R. Foster, E.J. Gane, E. Lawitz, S.B. Ho, I.M. Jacobson
Journal: Journal of Hepatology (2017)
Effect of inadequate access to radiologists on the benefits of screening mammography.
Authors: Nengliang Yao, Fabian Camacho
Journal: Journal of Clinical Oncology (2015)

e17527 Background: The benefits of breast cancer screening by mammography may be reduced because of insufficient follow-up diagnostic tests in underserved areas. This study examined the role of healthcare resources on the association between regular use of screening mammography and stage at diagnosis of breast cancer. Methods: A sample of 3,806 female patients diagnosed in 2007-2008 was identified in the data from cancer registry-Medicare linked data in four states (Kentucky, North Carolina, Ohio, and Pennsylvania). These women were enrolled in Medicare Part B on the months of their diagnosis, and for the two previous years, they were not members of a health maintenance organization and had diagnosis information not reported by autopsies or death certificates. A 3- to 24-month, pre-diagnosis look-back period was selected to classify prior use of screening mammography as evidence of recommended use of early detection service. Descriptive analyses and multivariate logistic regression were used to address research objectives. Results: Regularly screened women were more likely to be diagnosed at early stages than unscreened women in the Medicare population (92% vs 76%). The odds of detecting breast cancer at early stage among those screened women in a county with at least one radiologist is 5 times the odds of those unscreened (OR: 5.03; 95% CI: 3.66-6.90). The effects of mammography screening on early detection is smaller in women that lived in counties without a radiologist (OR: 2.54; 95% CI: 1.81-3.58; p = 0.0040). The predicted probability of detecting breast cancer at early stages for a screened women living in a county without a radiologist was 88%, smaller than in screened women living in a county with at least one radiologist (94%). Conclusions: Inadequate access to radiologists may reduce the effects of screening mammography on early detection of breast cancer. This research finding supports improving specialty care such as breast cancer diagnostic tests in areas where there are none to maximize the benefits of screening mammography. Telehealth and National Health Service Corps program may be able to play a role in reducing barriers to specialty care such as cancer diagnostics tests in rural areas.
Patient-specific immunotherapy utilizing putative tumor stem cells in patients with metastatic melanoma: A pooled analysis comparing tumor cell and dendritic cell vaccines in two phase II trials and a randomized phase II trial.
Authors: Robert Owen Dillman, Carol DePriest, Cristina de Leon, Neil M. Barth, Edward Francis McClay, Thomas Amatruda, Lee Steven Schwartzberg, Patrick Frank Sheehy, Khosrow Mahdavi, Cheryl Ann Mayorga, Robin Anne Ellis
Journal: Journal of Clinical Oncology (2012)

2569 Background: Metastatic melanoma is seldom cured, even in patients who achieve a complete remission, because new sites of disease emerge. Autologous, proliferating, self-renewing tumor cells (putative tumor stem cells and/or early progenitor cells), are critical to establishment of new depots of metastatic cancer, and may be excellent sources of antigen for vaccines. These trials addressed the impact on survival from immunizing with antigens from such cells. Methods: Data was pooled from 3 successive phase II trials, all of which included patients with documented metastatic melanoma, who were treated in protocols that utilized antigens from cell cultures of autologous tumor cells. S.C. injections were given weekly for 3 weeks, then monthly for 5 months. 1992-2000: 74 patients were injected with irradiated tumor cells (TC). 2000-2006: 54 patients were injected with autologous dendritic cells (DC) that had been co-cultured with irradiated autologous tumor cells (NCI-V01-1646). 2007-2011: in a randomized phase II trial, 24 patients were injected with TC, and 18 with DC (NCT00436930). Results: The table summarizes overall survival (OS) in each trial. In the pooled analysis there were 98 TC and 72 DC patients. Characteristics were similar in terms of age (51, 52), male gender (62%, 62%), no evidence of disease at the time of treatment (46%, 47%), and presence of M1c visceral disease at the time of treatment (13%, 14%). OS was longer in patients treated with DC (median 63.1 vs 20.2 months, 5-year OS 51% vs 26%, p=0.0002 Mantle-Cox log-rank test). The difference in OS in the randomized trial is also significant (p=0.007). Conclusions: Patient-specific DC vaccines primed with antigens from autologous proliferating, self-renewing tumor cells are associated with encouraging long-term survival rates, and are superior to patient-specific TC vaccines in populations of patients who have been diagnosed with metastatic melanoma. [Table: see text]
Khorana risk score: Is the body mass index a predictable factor for thromboembolism in European countries? A retrospective analysis.
Authors: Sandro Barni, Roberto Labianca, Melina Verso, Giampietro Gasparini, Erminio Bonizzoni, Mario Mandala, Matteo Brighenti, Fausto Petrelli, Carlo Bianchini, Tania Perrone, Giancarlo Agnelli
Journal: Journal of Clinical Oncology (2012)

e19612 Background: Five variables (site of cancer, platelet count, haemoglobin level, leukocyte count, and body mass index-BMI) define the Khorana risk score (KS), predicting the high (≥ 3), the moderate (1-2) and the low (0) risk of thromboembolic events (TEs) in cancer outpatients. Nadroparin has been demonstrated to reduce the incidence of TEs by about 50% in cancer outpatients receiving chemotherapy (PROTECHT study) and patients receiving chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Methods: 378 patients enrolled in the PROTECHT study didn’t receive thromboprophylaxis (placebo group) and were evaluable for the KS. The aim of this retrospective analysis was to assess the distribution of the five KS variables and if the replacing of BMI variable, in the KS, with a chemotherapy variable (administration of platinum compound or gemcitabine added 1point and their association 2points) in a PROTECHT score (PrS) could better predict high risk patients. A receiver operating characteristic (ROC) curve has been used to assess the accuracy of both scores. Results: Among patients the five KS variables were distributed as follow: 15% of stomach/pancreas cancer (2points), 33% with lung/gynecologic cancer (1point), 24% with platelet count of ≥350x10^9/L, 7.9% hemoglobin &lt;10g/dL , 14.3% leukocyte count &gt;11x10^9/L (1point each variable) and only 1.3% with BMI ≥ 35 (1point). 15 TEs occurred in the 378 pts, below the TEs distribution according to KS and PrS (see table). The area under the ROC curve was larger with PrS in comparison with KS (0.70 and 0.65 respectively). Conclusions: BMI ≥ 35 seems not to be a predictable factor for TEs in European cancer patients and the use of a chemotherapy variable could be more useful to identify patient at high risk of TE. A formal study is needed to evaluate which score could have a higher predictability to identify high risk patients for TEs. [Table: see text]