RESUMO
BACKGROUND AND AIMS: Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease-the principal causes of cancer mortality-have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are often not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular carcinoma (HCC) provides a compelling clinical correlate of this phenomenon. In response to TAE-induced ischemia, HCC cells adapt their growth program to effect a latent phenotype that precedes local recurrence. APPROACH AND RESULTS: In this study, we characterized and leveraged the metabolic reprogramming demonstrated by latent HCC cells in response to TAE-induced ischemia to enable their detection in vivo using dynamic nuclear polarization (DNP) magnetic resonance spectroscopic imaging (MRSI) of 13 carbon-labeled substrates. Under TAE-induced ischemia, latent HCC cells demonstrated reduced metabolism and developed a dependence on glycolytic flux to lactate. Despite the hypometabolic state of these cells, DNP-MRSI of 1-13 C-pyruvate and its downstream metabolites, 1-13 C-lactate and 1-13 C-alanine, predicted histological viability. CONCLUSIONS: These studies provide a paradigm for imaging latent, treatment-refractory cancer cells, suggesting that DNP-MRSI provides a technology for this application.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVES: Update our experience using radiotherapy (RT) for head-and-neck squamous or basal cell carcinoma with clinical perineural invasion (PNI) and correlate radiographic findings with outcomes. MATERIALS AND METHODS: We treated 65 patients with cT4N0 head-and-neck skin cancers with clinical PNI from 1965 to 2009 (N0 disease, 59; N1 disease, 6). Treatment included RT alone (N=18), RT with concurrent chemotherapy (N=14), surgery and postoperative RT (N=26), or postoperative RT with concurrent chemotherapy (N=5), and preoperative RT and surgery (N=2). Patients were stratified by imaging-negative disease (N=11), minimal or moderate peripheral disease (N=18), and macroscopic and/or central disease (N=36). Median RT dose was 72.6 Gy (50.4 to 79.2 Gy). Median follow-up overall and for living patients was 5.4 and 11.6 years, respectively. RESULTS: Five-year outcomes for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: local control, 81% versus 60% versus 47% (P=0.23); local-regional control, 80% versus 54% versus 47% (P=0.22); neck control, 100% versus 89% versus 93% (P=0.45); and distant metastasis-free survival, 89% versus 100% versus 93% (P=0.57), respectively. Five-year survival rates for imaging-negative disease versus minimal/moderate peripheral disease versus macroscopic/central disease were: overall survival, 82% versus 50% versus 52% (P=0.26), and cause-specific survival, 100% versus 58% versus 65% (P=0.08). Twenty-two (34%) patients had 1 or more severe (grade ≥3) late complications. CONCLUSIONS: There is a nonsignificant trend towards improved local control for imaging-negative patients and patients with minimal/moderate peripheral disease compared with macroscopic/central disease. Although survival appears better for imaging-negative patients, extent of imaging-positive PNI did not impact overall or cause-specific survival.