Publications (92) View all
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Article: Sequential Phase I and II Trials of Stereotactic Body Radiotherapy for Locally Advanced Hepatocellular Carcinoma.
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ABSTRACT: PURPOSETo describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).Patients And methodsTwo trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 2010. All patients had Child-Turcotte-Pugh class A disease, with at least 700 mL of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at 1 year (LC1y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: n = 50; Trial 2, 2007 to 2010: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in 14%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 61% had multiple lesions. Median gross tumor volume was 117.0 mL (range, 1.3 to 1,913.4 mL). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in 12%. LC1y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC1y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (1.1 to 7.7 months after SBRT). Median overall survival was 17.0 months (95% CI, 10.4 to 21.3 months), for which only TVT (HR = 2.47; P = .01) and being in Trial 2 (HR = 0.49; P = .01) were significant on multivariate analysis. CONCLUSION These results provide strong rationale for studying SBRT for HCC in a randomized trial.Journal of Clinical Oncology 04/2013; · 18.37 Impact Factor -
Article: Response to Letter to the Editor with Reference to article "Postoperative intensity-modulated radiotherapy following surgery for oral cavity squamous cell carcinoma: Patterns of failure"
Oral Oncology 03/2013; · 2.86 Impact Factor -
Article: Deintensification Candidate Subgroups in Human Papillomavirus-Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis.
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ABSTRACT: PURPOSETo define human papillomavirus (HPV) -positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM). PATIENTS AND METHODSOPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk.ResultsHPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02). CONCLUSIONHPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.Journal of Clinical Oncology 01/2013; · 18.37 Impact Factor -
Dataset: Author's personal copy Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer q
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ABSTRACT: s u m m a r y Objectives: To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). Methods: OPC treated with RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(À) cohorts. Results: Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p = 0.25) between the HPV(+) (n = 457) vs. the HPV(À) (n = 167) cases. While almost all (24/25) HPV(À) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(À). Post-DM survival rates were 11% vs. 4% at 2-years (p = 0.02) for the HPV(+) vs. HPV(À) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Conclusions: Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(À) patients: it may occur after a longer interval, often with a ''disseminating'' phenotype, and a small num-ber may have prolonged survival after salvage for DM. -
Article: Postoperative intensity-modulated radiotherapy following surgery for oral cavity squamous cell carcinoma: Patterns of failure.
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ABSTRACT: OBJECTIVES: To review outcomes and analyze the patterns of locoregional recurrence of oral cavity squamous cell carcinoma (OCSCC) treated with surgery and postoperative intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: All patients with Stage I-IVB OCSCC treated with surgery and postoperative IMRT± concurrent chemotherapy between 2005 and 2010 were evaluated. Patient survival and tumor outcomes were prospectively recorded. Outcome measures were 2year overall survival (OS), local control (LC), regional control (RC) and distant control (DC). Locoregional recurrences were spatially localized in relation to dosimetric plans. RESULTS: A total of 180 consecutive patients with median follow-up of 34months were identified. Disease subsites were oral tongue (46%), floor of mouth (23%), alveolus and hard palate (12%), buccal (9%), retromolar trigone (5%), and lip (4%). The 2year rates of OS, LC, RC, locoregional control (LRC), and DC were 65%, 87%, 83%, 78% and 83%, respectively. The 2-year estimated rates of LRC for larger subsites were: oral tongue (72%), floor of mouth (84%). Of the 180 patients, 38 (21%) had locoregional failure (LRF). Most LRFs were in-field (26, 68%) with 7 marginal and 5 out-of-field. Marginal/out-of-field failures occurred in the contralateral neck in N2b patients, at high level II/skull base, and in intentionally spared regions (near parotid) of pathologically involved necks. CONCLUSIONS: Nearly a third (12/38) of LR recurrences were marginal or out-of-field following postoperative IMRT for OCSCC. Postoperative IMRT following gross total surgical resection requires careful and comprehensive target volume delineation, and larger volumes may be needed than the primary RT setting.Oral Oncology 10/2012; · 2.86 Impact Factor
