tbuckley/cabot-search huggingface dataset:
Concordance and evaluation among IGCCCG and POG staging systems in pediatric germ cell tumors
Authors: J. Robles-Castro, R. Rivera-Luna, C. Calderon-Elvir, C. A. Leal-Leal
Journal: Journal of Clinical Oncology (2007)

20019 Background: The knowledge regarding treatment and prognosis of pediatric germ cell tumors has been taken from the development of these in the adult population. The object of this work was to compare the International Classification (IGCCCG) used in adults versus the POG classification used traditionally in a pediatric population. Methods: We reviewed clinical records from March 1994 through June 2003 with the diagnosis of malignant germ cell tumor of testis, retroperitoneal and mediastinum. All patients completed the treatment proposed initially with a follow up of more than 24 months. They were staged with the POG classification at diagnosis and with the International Classification for this study. Results: We obtained 61 patients with a 4 year follow up. They were all male, with germ cell tumor of testis or mediastinum. There were no retroperitoneal primary tumors. The age range was from 4 months to 188 months with an average of 48.7 months. Prognosis and treatment with the POG and the IGCCCG classifications had concordance of 0.0004 and 0.0371 respectively. Conclusions: We found limitations such as diverse chemotherapy protocols used in patients within the same risk group. Biological tumor Markers sampling play an important role in the the initial approach to allocate staging and risk based treatment protocols. It is necessary to carry out new studies with a homogeneous based population with similar diagnosis, treatment protocols and staging system to corroborate the utility and implementation of the International Classification in order to ameliorate morbidity and mortality of our pediatric patients. [Table: see text] No significant financial relationships to disclose.
Phase I/II study of adenovirus-interferon-γ (TG1042) in primary cutaneous lymphomas (CL)
Authors: M. Urosevic, P. Bleuzen, B. Acres, V. Bataille, P. Slos, G. Burg, P. Squiban, R. Dummer
Journal: Journal of Clinical Oncology (2004)

3039 Background: CL has been successfully treated with interferons (IFNs), which can offset the Th2 dominance associated with CL. Intratumoral (IT) injection of TG1042 (a non-replicating recombinant adenovirus with a human IFN-g cDNA insert) allows high local levels of IFN-g without severe toxicity induced by systemic delivery. Methods: We undertook a phase I/II, open-label, trial of repeated, IT injection of TG1042 in patients with advanced primary T cell (CTCL) and multilesional B cell (CBCL) cutaneous lymphomas. The designated lesions were injected on days 1, 8, and 15 with no injection in the fourth week (1 cycle) and thereafter up to 4 cycles. Immunohistochemistry and qPCR were performed on injected lesions biopsied at baseline and after each cycles. In the phase I, 9 patients were enrolled in 3 successive cohorts at the doses of 3x10E9 total particles (tp), 3x10E10 and 3x10E11 tp. In the phase II, 7 out of 27 additional planned patients have been treated at 3x10E11 tp. Results: To date 12 CTCL and 4 CBCL have been treated. Treatment is well tolerated with only one grade III toxicity. Injection site reaction is the most commonly observed adverse event. Local clinical response has been observed in 9 (5 complete responses) out of 14 evaluable patients. Disappearance of non-injected lesions was also observed and led to 7 overall responses (5 complete) out of 13 evaluable patients. Histology demonstrates pronounced differences in infiltrate patterns following treatment, with signs of vasculitis and increased numbers of eosinophils, neutrophils, CD8 and TIA-1+ve cells. CD4/CD8 ratio decreased in most tumors. Transgene-IFN-g mRNA was detectable in injected lesions. Gene expression analysis of biopsies and PBMC shows up-regulation of IFN-g and various immune response-associated genes. Conclusions: These data show the in situ immunological changes and resulting clinical responses following the administration of TG1042 and demonstrate a potential significant benefit for the treatment of cutaneous lymphoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Transgene Transgene Transgene
Survival prediction in terminally ill cancer patients by clinical estimates, laboratory and psychometric tests
Authors: S. Gripp, S. Moeller, R. Willers
Journal: Journal of Clinical Oncology (2006)

8578 Background: To improve general survival estimates in advanced cancer pat. we studied physicians’ clinical estimates, the impact of emotional disorders (anxiety and depression), and laboratory tests in palliative patients. Methods: From 12/03 to 7/04 patients with advanced cancer referred to radiation oncology for palliative treatment were invited to participate in this prospective cohort study. Pat. with adjuvant or curative treatment intent were not considered. The life span was independently estimated by two physicians and the institutional tumor board according to 3 categories (&lt;1, 1–6, and &gt;6 months). Agreement of survival predictions was analyzed with contingency tables and kappa statistics. Primary tumor, metastatic spread, performance status, pain, dyspnoea, weight loss, nausea, fatigue, serum enzymes (AP, LDH), function parameters (creatinine, bilirubin, CRP), and blood count (WBC, RBC) were also studied. Emotional disorders were measured using a validated psychometric self-assessment scale (Hospital Anxiety and Depression Scale, HADS). Life table analysis with log-rank test and stepwise Cox regression analysis with univariate significant variables were performed. Results: 216 pat. were enrolled and followed for at least 6 months. 580 prognoses were obtained. 94% (204) had complete blood tests. HADS questionnaires were completed by 71% (154). Survival was &lt;1 mo in 15% (33), 1–6 mo in 36% (78), and &gt;6 mo in 49% (105).Survival prediction was poor (kappa= 0.33) and consistently too optimistic (test of symmetry, p&lt;0.0001). In life table analysis primary tumor (hazard ratio 2.0), brain metastases, performance status (HR 1.9), dyspnoea (HR 2.0), nausea (HR 2.0), LDH (HR 1.9), WBC (HR 2.1), fatigue, anxiety and depression (HADS) were highly significant (p&lt; 0.0002). Conclusions: Physicians generally overestimated survival of advanced cancer patients emphasizing the need of objective prognostic models. Even short-term survival estimates (&lt; 1 mo.) were unreliable. Combined objective variables may improve survival prediction. Psychometric tests are promising candidates to be incorporated in more accurate prognostic models. No significant financial relationships to disclose.
Open-label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced nonresectable granulosa cell ovarian tumors: The GREKO II study.
Authors: Laia Garrigos, Ana Santaballa, Alicia Hurtado, Juan Francisco Rodriguez-Moreno, Ricardo Sanchez-escribano, Andres Redondo, Nuria Lainez, M Jesus Rubio, Isabel Bover, Juan Fernando Cueva, Susana Hernando Polo, Marta Izquierdo Manuel, Mario Prieto, Jose Antonio Lopez-Guerrero, Zaida Garcia-Casado, Ignacio Perez, Ramon De Las Penas, Enrique Grande, Jesús García-Donas
Journal: Journal of Clinical Oncology (2016)

TPS2598 Background: Granulosa-cell tumors (GCT) of the ovary are a rare entity characterized by a pathognomonic punctual mutation at the FOXL2 gene 402C→G (C134W). This alteration leads to an upregulaton of the enzyme CYP17 (key in androgens and 17-OH-progesterone synthesis). Interestingly, a previous study by our group has demonstrated clinical activity of ketoconazole, a well known CYP17 inhibitor (GREKO I trial). Additionally, cell cultures of both adult and juvenlie GCT showed an increased sensitivity to both ketoconazole and abiraterone compare to pancreatic tumors and lung adenocarcinoma. Orteronel (TAK700) is a selective inhibitor of 17, 20-lyase, that is being developed as an endocrine therapy for relevant hormone-sensitive cancers such as prostate and breast cancer. Orteronel is expected to suppress sex hormone levels in both circulation and relevant hormone-dependent malignant tissue. Thus we aimed to test the clinical activity of such drug in GCT. Methods: An open-label phase II single arm clinical trial has been designed for women with metastatic or locally advanced nonresectable granulosa cell ovarian tumor that harbors the somatic mutation FOXL2 402C→G (C134W) and who have not received prior treatment with any CYP17 inhibitor. Treatment consists on Orteronel 300mg BID, given orally, continuously in a 28-day treatment cycle. The primary objective is to assess the clinical benefit rate. Since this is an extremely unfrequent disease, 10 Spanish institutions are involved. 8 for the 20 planned cases have already been recruited. An extensive translational research will be included in order to improve our scarce knowledge of GCT. Clinical trial information: NCT02101684.
Clinical practice patterns of Radium-223 (R223) utilization and variables associated with completion of therapy.
Authors: Mary-Ellen Taplin, Susanna J. Jacobus, Matthew Fiorillo, Elisa M. Ledet, Patrick Cotogno, Allie E. Steinberger, Heather A. Jacene, Oliver Sartor, Rana R. McKay
Journal: Journal of Clinical Oncology (2015)

e16076 Background: R223, an alpha-emitting radioisotope, has emerged as a viable treatment option for patients with CRPC with bone metastases. Despite the benefits on quality of life and improvement in survival observed with R223, clinical practice patterns and utility of this agent are largely unknown. The objective of this study is to characterize the population of men receiving R223 commercially and evaluate clinical variables associated with completion of therapy. Methods: We conducted a pooled retrospective analysis of patients receiving R223 at DFCI (n = 54) and TCC (n = 58). Patients were classified into 2 therapy completion groups: received ≥ 5 doses vs < 5 doses and association with clinical variables was evaluated using Fisher’s exact test or Wilcoxon rank sum test, as appropriate. Results: While the majority of patients (56%) received ≥ 5 R223 doses, 20% (n = 22) received ≤ 2 doses. Patients receiving < 5 R223 doses were more likely to have a lower baseline Hgb (10.9 vs 12.1 g/dL), prior blood transfusion (18% vs 3%), higher LDH (421 vs 396 U/L), and shorter response to prior therapies (6.9 vs 9.7 months for abiraterone). The primary reason for treatment discontinuation included progression (61%) and toxicity (14%) with 21% of patients requiring ≥ 1 blood transfusion during treatment. Higher baseline Hgb (p = 0.007) and longer duration on abiraterone (p = 0.006) predicted for receipt of ≥ 5 R223 doses. At a follow-up of 10.5 months (mos), there were more deaths in the group of patients receiving < 5 doses of R223 compared to those receiving > 5 doses (51% vs 30%). Median overall survival for the total cohort was 16.4 mos (95% CI 11, 30). Conclusions: Initial analyses indicate that patients unable to complete R223 therapy have lower baseline Hgb with need for transfusion and possibly more aggressive disease given higher LDH and short response to prior therapy. It is hypothesized that use of R223 earlier in the disease natural history than the general current practice may be necessary to permit completion of recommend 6 doses. Understanding the clinical predictors associated with therapy completion will better inform the oncology community about optimal patient selection for R223.
Does Gleason pattern 5 influence the efficacy of enzalutamide against castration-resistant prostate cancer?
Authors: Tatsuya Shimomura, Hiroki Yamada, Takehito Naruoka, Keiichiro Mori, Kenichi Hata, Taro Igarashi, Takahiro Kimura, Shin Egawa
Journal: Journal of Clinical Oncology (2017)

e598 Background: In this study, we evaluated our cohort treated with enzalutamide retrospectively. We focused on Gleason pattern 5 prostate cancer which was very aggressive cancer and we investigated the difference in efficacy of enzalutamide between the groups including Gleason pattern 5 or not, to understand if initial aggressiveness of prostate cancer influence the enzalutamide responses. Methods: A total of 190 CRPC cases treated with enzalutamide between June 2014 and July 2016 at our university and affiliated institutions were included in this study. We evaluated clinical and pathological factors, Prostate specific antigen(PSA) responses, and overall survival, retrospectively. Results: Of these, 80 cases did not have Gleason pattern 5 and 110 cases had Gleason pattern 5 (Gleason Score 4+5, 5+4 or 5+5). Initial PSA level was higher and metastasis was more frequent in Gleason pattern 5 group (p = 0.0328, and 0.0171, respectively). Docetaxel pretreatment, abiraterone pretreatment, PSA and other serological data at starting enzalutamide were not different between the groups other than steroidal use (p = 0.0441). Overall survival rate at 1 year and 2 years were 84.3% and 77.2% in Gleason pattern 5 negative cohort, and 81.2% and 63.5% in Gleason pattern 5 cohort (p = 0.2459). There were no differences in terms of PSA responses between these groups. Mean PSA decline rate (pattern 5 negative vs. positive) were 57.1% vs. 54.6% (p = 0.6555). ≥ 50% PSA decline rate were 62.5% vs. 60.9% (p = 0.8329), ≥ 90% decline rate were 28.75% vs. 28.2% (p = 0.9317). Conclusions: In this study, we concluded that aggressiveness of initial status did not influence the efficacy of enzalutamide treatment. And disease status might be almost same when introducing enzalutamide. Of course, we need to recognize that initial androgen deprivation therapy (ADT) could be more efficient for lower Gleeson pattern than higher Gleeson pattern. However there is possibility that aggressiveness of prostate cancer cell would change through ADT and/or chemotherapy. We should investigate how prostate cancer is changing and should evaluate the prostate cancer cell status before starting treatment to predict the efficacy and to decide the treatment agents.
Flowcytometric Minimal Residual Disease Assessment in the EMN-02/HOVON-95 MM Trial: Used Methods and a Comparison of Their Sensitivity
Authors: Davine Hofste op Bruinink, Stefania Oliva, Lucie Rihova, Bronno van der Holt, Milena Gilestro, Jeroen G. te Marvelde, Pavla Vsianska, Alexander Schmitz, Helle Høholt, Hans Erik Johnsen, Mario Boccadoro, Roman Hajek, Pieter Sonneveld, Antonio Palumbo, Paola Omedè, Vincent H.J. van der Velden
Journal: Blood (2016)
Analysis of Bone Mineral Density, Biochemical Bone Turnover Markers and Serum Tryptase Levels in Patients with Systemic Mastocytosis (SM).
Authors: Akif S. Yavuz, Nilüfer Alpay, Öner Dogan, Nesimi Büyükbabani, Can Baykal, Dilsad Sindel, Yüksel Pekçelen, Refik Tanakol
Journal: Blood (2007)
Long-term survival of gastrointestinal cancer diagnosed in Hodgkin lymphoma survivors.
Authors: Lisanne Sara Rigter, Michael Schaapveld, Berthe M.P. Aleman, Cecile P.M. Janus, Anna M. van Eggermond, Augustinus D.G. Krol, Richard Van Der Maazen, Judith M. Roesink, Josee M Zijlstra, Gustaaf Willem Van Imhoff, Philip M. Poortmans, Max Beijert, Pieternella J. Lugtenburg, Otto Visser, Petur Snaebjornsson, Flora Van Leeuwen, Monique Esther van Leerdam
Journal: Journal of Clinical Oncology (2017)

40 Background: The risk of developing gastrointestinal (GI) cancer is increased in Hodgkin lymphoma survivors. This study aims to compare overall survival of GI cancer in Hodgkin lymphoma survivors with survival of first primary GI cancer patients. Methods: This cohort study compared overall survival of GI cancer patients in a Hodgkin lymphoma survivor population (HL-GI (n = 92) including esophageal (n = 25), gastric (n = 31), small intestinal (n = 2), colorectal cancer (n = 34)) with survival of a population-based cohort of first primary GI cancer patients (GI-1, n = 911) which was generated by individual matching of the 92 cases, based on tumor location, gender, age and year at diagnosis. Clinical characteristics were compared by Chi square tests. Cox regression was used for multivariable survival analysis (corrected for age, gender, and clinicopathological characteristics related to the GI tumor). Results: When comparing HL-GI and GI-1 patients, no differences in tumor stage, grade of differentiation or frequency of surgery were found. HL-GI patients were less frequently treated for their GI tumor with radiation therapy (7% vs. 24% in GI-1 patients, p &lt; 0.001) or chemotherapy (28% vs. 41%, p = 0.02). Overall 5-year and 20-year survival of HL-GI patients and GI-1 patients was non-significantly lower (28% vs. 38%, p = 0.13 and 19% vs. 29%, p = 0.06, respectively). This result was confirmed multivariably (5-year survival, p = 0.33, 20-year survival, p = 0.14). Also, for esophageal, gastric and colorectal cancer separately, no differences in overall survival were found between HL-GI patients and GI-1 patients. Conclusions: Long-term overall survival of GI cancer patients is similar in Hodgkin lymphoma survivors and first primary GI cancer patients. HL-GI patients did however receive less treatment with radiation therapy or chemotherapy. These treatments may not have been recommended due to prior Hodgkin lymphoma treatment or comorbidity. As risks of other causes of mortality are also increased in Hodgkin lymphoma survivors, the relatively good survival in this population is remarkable.
Survival in patients with locally advanced breast cancer after neoadjuvant docetaxel (T), carboplatin (C), and trastuzumab (H)
Authors: H. R. Chang, R. Prati, J. A. Gornbein, D. Chung, J. A. Glaspy
Journal: Journal of Clinical Oncology (2009)

e11573 Background: Neoadjuvant chemotherapy (NAC) has been widely used in patients with LABC. Although survival rates after neoadjuvant and adjuvant therapy are similar, NAC was shown to increase lumpectomy surgery and allow in vivo evaluation of treatment response. It is thought that pathologic complete response (pCR) after NAC by itself or together with other factors could predict overall survival (OS) and/or relapse free survival (RFS). Methods: Seventy-one of the 74 enrolled patients (mean tumor size=7.7cm) were analyzed. All patients received 4 cycles of T (75mg/m 2 ) and C (AUC=6) before and after surgery. HER2+ patients were randomized to receive either TCH or TC preoperatively; both received 1 year of H. Tumor size and nodal status were estimated clinically at baseline and pathologically after surgery. Bi &amp; multivariate analyses were performed on pCR, clinical and pathologic characteristics to predict OS and RFS. Hazard ratios (HR) are reported. Results: The median follow up was 2.0 years with 8 deaths and 9 recurrences. Nineteen (26.8%) had pCR. Kaplan-Meier RFS was 82.0% &amp; 54.2% and OS was 88.9% vs 70.6% at 3 years follow up for pCR &amp; non-pCR respectively. In the bivariate analysis, pCR (HR=0.32, p=0.114), lower tumor stage (p=0.097) and negative LN (p=0.0695) trended a favorable RFS. Lower tumor stage (p=0.032), negative LN (p=0.029) and lumpectomy surgery (p=0.023) were associated with better OS. In multivariate analysis, inflammatory breast cancer (p=0.041) and triple negative breast cancer-TNBC (p=0.044) predicted poor OS. Conclusions: With few deaths/recurrences we were unable to conclusively identify predictors for OS or RFS. Inflammatory and TNBC remain poor prognosticators for OS and RFS. pCR was a suggestive predictor (HR&lt;1) but not statistically significant probably due to low sample size and high number of pCR cases that were TNBC. [Table: see text]
Efficacy of concurrent cetuximab (C225) versus 5-fluorouracil/carboplatin (5FU/CBDCA) or cisplatin (CDDP) with intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNSCC).
Authors: Lauren Quinn Shapiro, Eric Jeffrey Sherman, Lawrence Koutcher, Jeremy Setton, Zhigang Zhang, Weiji Shi, Shyam S. Rao, Matthew G. Fury, Suzanne L. Wolden, Dennis Kraus, David G. Pfister, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2012)

5537 Background: We reported inferior outcomes for LAHNSCC patients (pts) that received concurrent C225 vs. high-dose CDDP with IMRT (IJROBP 2011; 81:915). Prior to FDA approval of C225 for LAHNSCC, non-CDDP candidates at our institution were treated with 5FU/CBDCA (JNCI 1999; 91:2081). The purpose of this study was to compare the outcomes of concurrent C225 vs. 5FU/CBDCA vs. CDDP with IMRT for LAHNSCC. Methods: Retrospective review of records was performed for pts treated at MSKCC with concurrent C225 (n=49) vs. 5FU/CBDCA (n=52) vs. high-dose CDDP (n=259) and IMRT from 11/02 to 04/08. Overall survival (OS), locoregional failure-free survival (LRFS), and late toxicity for all pts and oropharyngeal subset were obtained. Outcomes were analyzed using univariate/multivariate Cox proportional hazards model or competing-risks analysis. Multivariate OS analysis was confirmed by propensity score adjustment. Results: Pts were similar with regard to site, overall stage, and alcohol/tobacco history. Compared to pts treated with CDDP, those who received C225 or 5FU/CBDCA were older, with lower performance status, higher Charlson score, higher T stage, and worse renal function. With median follow-up of 53.1 months for survivors, the 4-year OS was 40.9% (95% CI 26.0-55.2%) for C225 vs. 70.2% (95% CI 55.5-80.9%) for 5FU/CBDCA vs. 86.9% (95% CI 82.0-90.6%) for CDDP. Compared with CDDP, C225 (hazard ratio [HR] 4.01, p&lt;0.0001) but not 5FU/CBDCA (HR 1.54, p=0.15) was associated with worse OS on multivariate analysis. Propensity score analysis yielded a HR of 2.76 (p=0.01) for treatment with C225 vs. platinum-based chemotherapy. 4-year actuarial LRF for 5FU/CBDCA was similar to CDDP (9.7% vs. 6.3%, HR 1.51, p=0.42 by Gray’s method) and significantly lower than C225 (40.2%, HR 4.95, p=0.002). Late toxicity was as follows: C225 (6.1%) vs. CDDP (7.7%) vs. 5FU/CBDCA (21.2%). Conclusions: After adjusting for independent risk factors, there was no significant difference in OS or LRFS between 5FU/CBDCA and high-dose CDDP, but C225/RT resulted in significantly inferior OS and LRFS. Late toxicity was worst with 5FU/CBDCA.