ABSTRACT
PURPOSE: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.
Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Cisplatin/therapeutic use , Cyclin-Dependent Kinase Inhibitor p16/analysis , Oropharyngeal Neoplasms/therapy , Papillomaviridae/isolation & purification , Pharyngectomy , Radiotherapy, Intensity-Modulated , Squamous Cell Carcinoma of Head and Neck/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Chemoradiotherapy, Adjuvant , Cisplatin/adverse effects , Feasibility Studies , Female , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/chemistry , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Pharyngectomy/adverse effects , Progression-Free Survival , Prospective Studies , Radiotherapy, Intensity-Modulated/adverse effects , Squamous Cell Carcinoma of Head and Neck/chemistry , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/virology , Time FactorsABSTRACT
Angiomatoid "malignant" fibrous histiocytoma is a rare sarcoma of low malignant potential that occurs most commonly in the extremities of children and young adults. Herein, we present a case of angiomatoid malignant fibrous histiocytoma with unusual histologic features arising in the mediastinum of an 80-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma. The tumor cells expressed epithelial membrane antigen and desmin. Cytogenetic analysis revealed the translocation t(2;22)(q33;q12). Molecular genetic analysis confirmed the rearrangement of the EWSR1 locus and the presence of the EWSR1/CREB1 fusion. This report expands the clinicopathologic spectrum of angiomatoid malignant fibrous histiocytoma and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants.
Subject(s)
Histiocytoma, Malignant Fibrous/pathology , Mediastinal Neoplasms/pathology , Aged, 80 and over , Calmodulin-Binding Proteins/genetics , Chromosomes, Human, Pair 2/genetics , Chromosomes, Human, Pair 22/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Cytogenetic Analysis , Histiocytoma, Malignant Fibrous/genetics , Humans , Male , Mediastinal Neoplasms/genetics , Oncogene Proteins, Fusion/genetics , RNA-Binding Protein EWS , RNA-Binding Proteins/genetics , Translocation, GeneticABSTRACT
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces Parkinsonism in humans, monkeys, and mice and oxidative stress in mammalian cells and tissues. In the present study, the relationship between the generation of lipid peroxidation products and DNA damage was studied in mice treated with MPTP. The frequency of micronucleated polychromatic erythrocytes (MN-PCE) and the concentrations of malonaldehyde and 4-hydroxyalkenals were determined in the bone marrow and peripheral blood of mice 0, 24, 48, 72, and 96 hr after treatment with MPTP, cyclophosphamide as a positive control, or diluent. Both MN-PCE and the lipid peroxidation products increased in MPTP-treated mice, with significant levels being detected in bone marrow starting at 24 hr after treatment and in blood starting at 48 hr after treatment. These results suggest that the generation of oxidative products is related to the DNA damage produced by MPTP in mice.