tbuckley/cabot-search huggingface dataset:
Multimodal Treatment of Malignant Sacrococcygeal Germ Cell Tumors: A Prospective Analysis of 66 Patients of the German Cooperative Protocols MAKEI 83/86 and 89
Authors: U. Göbel, D. T. Schneider, G. Calaminus, H. Jürgens, H. J. Spaar, W. Sternschulte, K. Waag, D. Harms
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P = .01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P &lt; .001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 ± 0.05 (50 of 66 patients), and overall survival was 0.81 ± 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 ± 0.09 (16 of 19 patients) versus 0.45 ± 0.15 (five of 11 patients), P = .01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.
Assessment of the current implementation and barriers to uptake of the guidelines for the psychosocial care of adults with cancer according to cancer nurses in Australia.
Authors: Catalina Lawsin, Kirsty McMillan, Phyllis Butow, Jane Turner, Patsy Yates, Moira Stephens, Sylvie D. Lambert, Kathryn White
Journal: Journal of Clinical Oncology (2013)

e20615 Background: The Clinical Practice Guidelines for the Psychosocial Care of Adults with Cancer (the Guidelines) were launched in 2003 to guide cancer care providers in the assessment of psychosocial issues and provision of evidence-based interventions. Despite multi-faceted Australia-wide dissemination efforts, the current study aimed to be the first to assess current implementation of the Guidelines across and barriers to uptake. Methods: A cross-sectional web-based survey was developed to assess clinical use of recommendations in the Guidelines in relation to the provision of psychosocial support, and assessment of distress and pain. Data was collected about perceived barriers to the provision of psychosocial support at participants’ place of employment, as well as roles and training needs. Cancer nurses were recruited through the Cancer Nurses Society of Australia, the Royal College of Nursing Australia, and the Haematology Society of Australia &amp; New Zealand. Descriptive and correlational analyses were conducted. Results: Of 354 respondents, 266 completed the assessment. Relaxation training was the most prevalent form of psychosocial support (24%) and web-based support (20%) was the most common modality. While 26% of institutions had no systematic means of assessing distress amongst patients, those that did relied primarily on clinical interviews (37%). Once a patient was identified as distressed, most often the care coordinator was responsible for providing ensuing interventions. An organizational culture in which psychosocial issues are seen as less important than medical treatment (23%) and role ambiguity proved to be barriers to provision of psychosocial support, particularly when nurses did not perceive psychosocial support was beneficial and supervision was inadequate (R 2 = .313, F(1, 265) = 6.58, p &lt; .001). Conclusions: Results confirmed that dissemination does not necessarily equal implementation. Clear pathways for assessment and treatment need to be established to reduce individual barriers and promote organizational cultures that appreciate the need to integrate psychosocial care in standard medical treatment.
A specific nomogram to predict subsequent brain metastasis in metastatic triple-negative breast cancer patients
Authors: L. Pusztai, R. Rouzier, L. Pusztai, N. Ibrahim
Journal: Journal of Clinical Oncology (2009)

1028 Background: The development of brain metastases is usually a fatal event in the history of breast cancer patients with metastatic disease other than brain (MDOB). We previously developed a global nomogram that includes immune-histochemical phenotype to predict the occurrence of brain metastasis (BM). We hypothesized that a nomogram specific to triple negative tumor (TN) could improve prediction BM occurrence in patients with MDOB, thus allowing allocation of preventive treatment more efficiently. Methods: Patients with metastatic BC presenting between 2000 and February 2007 treated at M. D. Anderson Cancer Center were included in this retrospective analysis. We tested 17 variables and developed a multivariate model to predict occurrence of subsequent BM in TN tumors and created a nomogram that could be used for individual prediction. The model was cross-validated by bootstrapping and compared to the global nomogram. Results: Among 2,136 patients with metastatic breast cancer including 641 patients with TN tumors, 362 developed BM during follow-up: young age, histological characteristics, short delay between initial diagnosis and MDOB, number of metastatic sites and initial number of metastatic nodes were significantly and independently associated with subsequent BM. The nomogram to predict BM developed on the TN population provided a better discrimination (area under the ROC curve [AUC] = 0.62) than the global nomogram (AUC = 0.58) for the TN tumors. Prediction with the specific nomogram and the global nomogram were highly correlated (correlation factor = 0.67, p &lt; 0.0001). However, when a threshold at 15% was used, we observed 27% of discordant cases and the sensitivity of the specific nomogram was better. Conclusions: We developed a specific tool to predict subsequent BM in patients with metastatic TN breast cancer. This nomogram outperformed a global nomogram. No significant financial relationships to disclose.
Initial results of a pilot study of epratuzumab and rituximab in combination with CHOP chemotherapy (ER-CHOP) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL)
Authors: I. N. Micallef, B. S. Kahl, U. Gayko, A. Cesano, S. M. Ansell, S. Geyer, D. J. Inwards, M. J. Maurer, S. Horning, T. M. Habermann
Journal: Journal of Clinical Oncology (2004)

6580 Background: A pilot study was performed at Mayo Clinic Rochester and University of Wisconsin Madison, to assess the feasibility of combination ER-CHOP in patients (pts) with newly diagnosed DLBCL. Methods: Therapy was given as follows: Epratuzumab 360mg/m2 followed by Rituximab 375 mg/m2 and standard dose CHOP q 3 weeks for 6–8 cycles. Primary endpoint was safety and tolerability as determined by the incidence of grade 4 neutropenia and grade 3–4 antibody infusional toxicity; secondary endpoints were efficacy as determined by the CR rates, overall response rates (ORR) and 9-month progression free survival. Weekly CBCs were obtained to monitor hematological toxicity. Growth factor (GF) support was added to subsequent cycles for all pts who experienced grade 4 neutropenia. Subsequent neutropenia mandated a dose reduction of chemotherapy. Results: As of December 2003, all 15 pts have been entered on protocol. Baseline pt characteristics included median age 63 years (range 42–78); 10 pts (67%) were male. Most pts had advanced stage; majority had a low (46%) or intermediate (46%) IPI. Five pts (33%) had an elevated LDH. Performance score was 0–1 in 14 pts. Overall 88 cycles are evaluable for toxicity and the incidence of grade 4 neutropenia was 31%. 13 of 15 pts (87%) developed grade 4 neutropenia. Nine pts required dose reductions. No pt developed grade 3 antibody infusion related toxicity. Other hematological toxicities included anemia (grade 3:2 pts; grade 4:1 pt) and thrombocytopenia (grade 3:2 pts). Non-hematological grade 3 or 4 toxicities included cardiac (grade 4:1 pt), neurologic (grade 3:1 pt, grade 4:1 pt) and pulmonary (grade 4:1 pt). Fourteen pts were assessable for response; 7(50%) CR, 5(36%) PR, 1 stable disease and 1 progressed. The ORR was 12 of 14 (86%, 95% CI [57%, 98%]). At a median follow-up of 8.1 months (range 0–14.6 months), 14 of 15 pts remain alive without progression. Conclusions: We conclude that ER-CHOP every 21 days is feasible for newly diagnosed pts with DLBCL. Further studies are needed to fully assess efficacy of this regimen in this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IDEC; Amgen
Association of p53 codon 72 polymorphism with resistance to adjuvant therapy in primary breast cancer
Authors: T. Toyama, Z. Zhang, M. Hamguchi, N. Kondo, H. Iwase, H. Iwata, S. Takahashi, H. Yamashita, Y. Fujii
Journal: Journal of Clinical Oncology (2007)

10520 Background: Single-nucleotide polymorphisms (SNPs) in codon 72 of the p53 gene and in the promoter region of the MDM2 gene (SNP309) have been suggested to play a role in many cancers. We investigated whether these SNPs were associated with patient outcome and influence of adjuvant systemic therapy. Method: The genotypes of p53 codon 72 and MDM2 SNP309 were defined among 557 primary Japanese breast cancer patients (median follow-up, 61.7 months). The effects of several variables on survival were tested by Cox's proportional hazards regression analysis. Results: We showed that the Pro/Pro genotype of p53 codon 72 was significantly associated with poorer disease-free survival (DFS) than other genotypes by Kaplan-Meier analysis (P = .049) and multivariate Cox's proportional hazards regression analysis (P = .047, risk ratio of recurrence = 1.67), whereas MDM2 SNP309 status was not associated with DFS. The association of the Pro/Pro p53 genotype with poorer DFS was especially significant in patients who received adjuvant chemotherapy (P = .009). In contrast, among the patients who had received adjuvant hormonal therapy or no adjuvant systemic therapy, p53 codon 72 genotype was not associated with DFS. Conclusion: The Pro/Pro genotype of p53 codon 72 appears to be an independent prognostic marker of breast cancer patients that have received adjuvant systemic therapy, particularly chemotherapy, and may be predictive of therapy resistance. [Table: see text] No significant financial relationships to disclose.
Protective effect of metformin in lung cancer patients
Authors: B. Gagnon, M. Roseman, G. Kasymjanova, N. MacDonald, H. Kreisman, D. Small
Journal: Journal of Clinical Oncology (2009)

e22063 Background: Over the past decade, dozens of studies have shown that metformin not only decreases mortality in diabetics, it also significantly reduces CRP and reduces the risks of cancer in rodent and human cell lines. We report on the survival of lung cancer patients concomitantly exposed to metformin in our community-based program. Methods: 850 patients undergoing treatment from a prospectively collected pulmonary oncology database of the SMBD-Jewish General Hospital over an 8-year period were analyzed. Pilot observational study of survival was performed using Cox regression model. The factors that were included in the model were age, gender, stage, histology and metformin use. Results: 850 patients (F: M=375:475; mean age of 66) were diagnosed since 2000 and followed in pulmonary oncology outpatient clinic for NSCLC. 523 (62%) of those patients were diagnosed with adenocarcinoma; 488 (57%) were stage IIIB with pleural effusion/IV. 79(9%) patients were receiving treatment with metformin for their comorbid type 2 diabetes. The Cox regression analysis demonstrated that age, gender, stage and use of metformin were significant prognostic factors for survival. The use of metformin is associated with a 37% (HR 1.37; CI 1.01–1.84) (p=0.039) increase in survival. Conclusions: Thus, the result obtained from our model suggests that use of metformin may be associated with better survival of lung cancer patients. As this is a pilot study, we will consider alternative explanations. No significant financial relationships to disclose.
Landscape and evolutionary dynamics of terminal repeat retrotransposons in miniature in plant genomes
Authors: Dongying Gao, Yupeng Li, Kyung Do Kim, Brian Abernathy, Scott A. Jackson
Journal: Genome biology (2016)

Terminal repeat retrotransposons in miniature (TRIMs) are a unique group of small long terminal repeat retrotransposons that are difficult to identify. Thus far, only a few TRIMs have been characterized in the euphyllophytes, and their evolutionary and biological significance as well as their transposition mechanisms are poorly understood.Using a combination of de novo and homology-based methods, we annotate TRIMs in 48 plant genome sequences, spanning land plants to algae. The TRIMs are grouped into 156 families including 145 that were previously undefined. Notably, we identify the first TRIMs in a lycophyte and non-vascular plants. The majority of the TRIM families are highly conserved and shared within and between plant families. Unlike other long terminal repeat retrotransposons, TRIMs are enriched in or near genes; they are also targeted by sRNAs between 21 and 24 nucleotides in length, and are frequently found in CG body-methylated genes. Importantly, we also identify putative autonomous retrotransposons and very recent transpositions of a TRIM element in Oryza sativa.We perform the most comprehensive analysis of TRIM transposons thus far and report that TRIMs are ubiquitous across plant genomes. Our results show that TRIMs are more frequently associated with large and CG body-methylated genes that have undergone strong purifying selection. Our findings also indicate that TRIMs are likely derived from internal deletions of large long terminal repeat retrotransposons. Finally, our data and methodology are important resources for the characterization and evolutionary and genomic studies of long terminal repeat retrotransposons in other genomes.
Chemoimmunotherapy reinduction with epratuzumab in children with ALL with marrow relapse: A Children's Oncology Group (COG) pilot study (ADVL04P2)
Authors: E. A. Raetz, M. S. Cairo, M. J. Borowitz, S. M. Blaney, M. D. Krailo, T. A. Leil, D. M. Goldenberg, W. A. Wegener, W. L. Carroll, P. C. Adamson
Journal: Journal of Clinical Oncology (2007)

9513 Background: CD22, a 135kd protein restricted to B-cells, is expressed in &gt; 90% of childhood B-precursor acute lymphoblastic leukemia (ALL). We conducted a feasibility/phase 2 study of epratuzumab, a humanized monoclonal antibody against CD22, with reinduction chemotherapy in children with relapsed CD22+ ALL. Methods: The feasibility portion (n=12) of the study is reported here. Patients with first or later ALL marrow relapse at any time following diagnosis, ± extramedullary disease, with = 25% blasts expressing CD22 and a presenting white blood cell count (WBC) of = 50,000/μl, were eligible. Therapy consisted of a 14-day single agent phase (epratuzumab 360 mg/m 2 /dose IV twice weekly × 4 doses), followed by 4 weekly doses of epratuzumab in combination with standard reinduction chemotherapy (vincristine, prednisone, PEG-asparaginase, doxorubicin). Remission induction rates and minimal residual disease (MRD) by flow cytometry were determined at the end of this 6-week period. PK studies were performed by ELISA based immunoassay (prior + 30 minutes after infusions). Results: 12 evaluable patients, median age 10 years (range 3 - 18), were accrued. 9 pts were in 1st (n=5 early; n=4 late), and 3 pts in 2nd or later marrow relapse. The mean (±SD) trough epratuzumab concentration increased from 69±23 to 232±74 μg/ml during the initial 14 days. Surface CD22 was not detected by flow cytometry on peripheral blood leukemic blasts within 24 hours of drug administration in all but one patient, indicating effective targeting of leukemic cells by epratuzumab. The most frequent toxicities were grade 1–2 infusion reactions (n=9). Two dose limiting toxicities occurred: one patient had a Grade 4 seizure of unclear etiology and one patient had asymptomatic Grade 3 ALT elevation. 9 patients achieved a complete remission following chemoimmunotherapy, of whom 7 were MRD-negative. Conclusions: Treatment with epratuzumab plus standard reinduction chemotherapy is feasible and well tolerated in children with relapsed ALL, producing favorable early responses in the majority of patients. The phase II portion of the study is ongoing. [Table: see text]
Complete response (CR) to ifosfamide, gemcitabine, and vinorelbine (IGEV) and outcome in relapsed/refractory Hodgkin's lymphoma (HL) patients
Authors: A. Anastasia, R. Mazza, L. Giordano, M. Balzarotti, M. Magagnoli, L. Castagna, M. Spina, M. Michieli, U. Tirelli, A. Santoro
Journal: Journal of Clinical Oncology (2009)

8568 Background: High dose chemotherapy with autologous stem cells transplant (ASCT) is the gold standard in patients with relapsed/refractory HL. Response to induction chemotherapy (chemosensitive patients) plays a major role in prognosis, however the role of CR status after induction therapy has not been established. Methods: One hundred twenty one patients with relapsed/refractory HL received 4 courses of IGEV followed by single (N=59) or tandem (N=19) ASCT (Santoro et al., Haematologica 92, 2007). Response to IGEV was evaluated by Cheson criteria (1999).The aim of this study was to evaluate the role of CR versus no-CR to IGEV induction therapy on the outcome in terms of progression free survival (PSF) and overall survival (OS). Statistical analysis was performed by using the Kaplan-Meier method and Cox proportional hazard model. Results: IGEV induced an overall response rate of 75% with 46% of CR. In the univariate analysis favourable factors for outcome were CR vs no-CR to IGEV (PFS: p &lt;0.001, OS: p 0.002), A vs B symptoms (PFS: p 0.003; OS: p 0.05), limited vs advanced stage (PFS: p 0.03; OS: p 0.03), and 1 vs≥2 previous chemotherapy lines (PFS: p 0.03, OS: p 0.02); response to last therapy (relapsed vs refractory) influenced PFS (p 0.03) but not OS (p 0.70). The multivariate analysis confirmed the favourable prognostic role of CR to IGEV (PFS HR: 2.5, CI 95%:1.3; 4.6 - OS HR 2.3, CI 95%:1.1;4.8) and of the number of previous chemotherapy lines (PFS HR:1.8, CI 95%:1.0;3.2 - OS HR 2.1, CI 95%:1.1;3.9). Conclusions: According to our data, we conclude that: 1. CR to IGEV is the strongest indicator of outcome in relapsed/refractory HL. 2. Achievement of CR to IGEV overcomes the role of initial disease status. 3. Efforts are warranted to increase the CR rate by induction therapy. No significant financial relationships to disclose.
Vinorelbine, cisplatin, and continuous infusion of 5-fluorouracil (ViFuP regimen) in carcinoma of unknown primary
Authors: L. Fumagalli, M. Locatelli, G. Curigliano, R. Ghisini, N. Fazio, F. Nolè, A. Goldhirsch
Journal: Journal of Clinical Oncology (2009)

e20682 Background: Carcinoma of unknown primary (CUP) is rarely encountered in clinical practice, 3–5% of all new cancers, and several types of chemotherapy regimens have not yielded satisfactory results. Methods: We evaluated feasibility and efficacy of combined vinorelbine 20 mg (V) on day 1 and 3, continuous infusion 5-fluorouracil (5-Fu) 200 mg/m 2 days 1–21 and cisplatin (C) 60 mg/ m 2 day 1, 21 (ViFuP regimen) therapy in patients (pts) with CUP. Each course was repeated every 21 days for up to six cycles, followed by 5-FU continuous infusion in case of response or clinical benefit. Results: Twenty-six consecutive pts with CUP were enrolled in the study, 14 females and 12 males. Median age was 58 years (range 35–72). All pts are evaluable for response and toxicity. All pts were chemotherapy-naïve with the exception of 2 who had received prior 5-Fu and folinic acid (1 pt) and paclitaxel and adriamicin (1 pt). Objective responses were observed in 27% [6 PR (23%), 1 CR (4%)], while SD in 35% (9) of the pts (overall clinical benefit 52%). Ten patients had PD (38%). The median time to progression TTP was 4.0 months (range 1–98). Data on overall survival will be presented. Toxicity profile was particularly favorable. The most frequent grade 3–4 adverse events were leukopenia (8%), neutropenia (11 %) and anemia (3%). Conclusions: ViFuP was found to be an effective and well tolerated regimen in patients with CUP. Efficacy, control of symptoms and lack of significant alopecia were particularly appreciated. This regimen may be viewed as a standard of care in patients with fair good performance status, alternative to other systemic platinum-based chemotherapy regimens, in cases in which anthracyclines are contraindicated, or when patient's preference leads to the choice of a combination of drugs which does not cause significant alopecia. No significant financial relationships to disclose.