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New Haven, CT, United States

Hsu C.-H.,National Taiwan University Hospital | Kang Y.K.,University of Ulsan | Yang T.-S.,Chang Gung Memorial Hospital | Shun C.-T.,National Taiwan University Hospital | And 7 more authors.
Oncology (Switzerland) | Year: 2013

Objectives: The bevacizumab/erlotinib combination was reported with high clinical activity for advanced hepatocellular carcinoma (HCC) by a phase II study conducted in the USA. This multicenter study across several Asian countries was to evaluate the safety and efficacy of the combination in this population. Methods: Patients with histology-proven HCC, advanced disease and Child-Pugh class A liver function received bevacizumab 5 mg/kg intravenously every 2 weeks and erlotinib 150 mg/day orally as first-line therapy. The primary end point was progression-free survival at 16 weeks (PFS-16W). The expression of epidermal growth factor receptor (EGFR), phospho-AKT and vascular endothelial growth factor, the microvessel density and the EGFR gene copy number in HCC tissues were correlated with treatment efficacy. Results: Fifty-one patients were enrolled. The PFS-16W was 35.3% (95% CI 22.4-49.9), the median PFS was 2.9 months (95% CI, 1.3-4.4) and the median overall survival was 10.7 months (95% CI, 6.2-15.2). Grade 3/4 toxicities were uncommon, including rash, acne (10% each), diarrhea (6%) and gastrointestinal bleeding (4%). None of the evaluated biomarkers correlated with disease control or PFS. Conclusions: Bevacizumab plus erlotinib showed good tolerability and modest activity in this Asian cohort. Further studies are warranted to identify the predictive biomarkers of this combination. Copyright © 2013 S. Karger AG, Basel. Source

Hagemann I.S.,Genomics and Pathology Services | Govindan R.,Section of Medical Oncology | Javidan-Nejad C.,Washington University in St. Louis | Pfeifer J.D.,Genomics and Pathology Services | Cottrell C.E.,Genomics and Pathology Services
Journal of Thoracic Oncology | Year: 2014

Precision medicine uses individually determined genomic information to guide treatment in cancer and other diseases. We have implemented a clinical genomics assay that uses targeted next-generation sequencing of 25 cancer-related genes to guide the use of targeted therapies in diverse malignancies. We report the case of a 55-year-old woman with a poorly differentiated squamous cell carcinoma of thymic origin, with disease progression after standard treatment. Targeted tumor sequencing revealed the presence of a KIT codon 579 deletion (p.D579del). This specific mutation has not previously been associated with thymic tumors, but has been reported in gastrointestinal stromal tumors and has been associated with response to imatinib. Imatinib therapy was instituted for and resulted in stabilization of disease. This case illustrates the potential of clinical next-generation sequencing to open unexpected avenues for treatment and thereby improve patient outcomes. Copyright © 2013 by the International Association for the Study of Lung Cancer. Source

Filosso P.L.,University of Turin | Yao X.,Section of Medical Oncology | Ahmad U.,Sloan Kettering Cancer Center | Zhan Y.,Section of Medical Oncology | And 8 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2015

Objective: Primary neuroendocrine tumors of the thymus (TNET) are exceedingly rare. We studied a large series of TNET identified through the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons databases. Methods: This was a retrospective multicenter study of patients undergoing operation for TNET between 1984 and 2012. Outcome measures were: overall survival (OS) and cumulative incidence of recurrences (CIR). OS was analyzed using the Kaplan-Meier method and CIR was analyzed using competing risk analysis. Associations with clinical and prognostic factors for OS and CIR were evaluated using the log rank test and Gray test. Results: Two hundred five patients with TNET were treated: 25 patients received induction therapy (19 chemotherapy [CT] and 6 radiotherapy [RT]). Data about resection status were available in 47% of cases: complete resection was performed in 52 patients (54%). Masaoka-Koga stages I, II, III, and IV were observed in 12, 33, 56, and 47 patients, respectively. Atypical carcinoid was the commonest histologic subtype (71 cases; 40%). One hundred one patients with TNET received adjuvant treatment; 52 patients died and 36 experienced a recurrence. The median OS was 7.5 years; 5-year OS was 68%, and 5-year CIR was 39%. OS was significantly influenced by Masaoka-Koga stage (P = .02) and completeness of resection (P = .03). CIR significantly increased in high Masaoka-Koga stages (P = .04). Histologic subtype was not associated with either OS or CIR. Conclusions: Our results confirm the high biologic aggressiveness of these rare neoplasms; pathologic stage and completeness of resection were demonstrated to be strong prognostic factors, whereas histology did not influence patients outcome. Copyright © 2015 by The American Association for Thoracic Surgery. Source

Koumarianou A.,Section of Medical Oncology | Karageorgopoulou S.,Section of Medical Oncology | MacHairas A.,Attikon University Hospital | Liakakos T.,Attikon University Hospital | And 4 more authors.
Case Reports in Oncology | Year: 2012

A 59-year-old male presented with a painful right inguinal swelling and deep vein thrombosis at the ipsilateral leg. An inguinal hernia was initially diagnosed, but during surgery a large mass was found anteriorly to the peritoneal sheaths. Histology revealed a high-grade pleomorphic rhabdomyosarcoma. The mass advanced rapidly, occupying the whole right iliac fossa and metastasizing to the lung. Despite first- and second-line chemotherapy, the patient deteriorated rapidly and died. Rhabdomyosarcomas should be managed in specialized centres as they have prognostic factors and histologic features still controversial and poorly clarified. Copyright © 2012 S. Karger AG, Basel. Source

Correale P.,Section of Medical Oncology | Rotundo M.S.,University of Catanzaro | Del Vecchio M.T.,University of Siena | Remondo C.,Section of Medical Oncology | And 9 more authors.
Journal of Immunotherapy | Year: 2010

Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies, like GOLFIG chemoimmunotherapy (gemcitabine, oxaliplatin, 5-fluorouracil/folinic acid, granulocyte macrophage colony-stimulating factor, and aldesleukine), that resulted a safe and very active regimen. Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs, increase of central memory T cells, and decrease of regulatory T cells (Treg) in the peripheral blood. We thus investigated a potential correlation between the Treg tumor infiltration at diagnosis and the clinical outcome in a current randomized phase 3 trial aimed to compare the GOLFIG regimen with the standard FOLFOX chemotherapy (GOLFIG-2). An immunohistochemistry study was carried out to quantify the infiltration of Treg/FoxP3+ T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. Treg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progressionfree survival (PFS). Higher T reg tumor infiltration scores were associated with a better prognosis in the whole series (Treg high score vs. low score: overall survival= mean 43.2 mo vs. 28.6 mo, P= 0.0005) and a better outcome after treatment (Treg high score vs. low score: PFS=mean 15.8mo vs. 8.8 mo, P=0.0009; treatment-relative survival=mean 23.1mo vs. 18.2 mo, P =0.004). PFS was significantly longer in GOLFIG high versus all other subgroups (mean 18.1mo vs. 9.9 mo, P =0.01). Our results suggest that a higher FoxP3+ T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy. Copyright © 2010 by Lippincott Williams & Wilkins. Source

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