Proton Beam Therapy for Hepatocellular Carcinoma Associated with Portal Vein Tumor Thrombosis

Background and Purpose: The prognosis of patients with advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is extremely poor, as effective treatment options are limited. The authors performed a retrospective review to evaluate the efficacy of proton-beam therapy (PBT) for patients presenting with PVTT in the setting of HCC.Patients and Methods: Between February 1991 and September 2005, 35 patients with HCC and tumor thrombi in the main trunk or major branches of the portal vein presented for consideration of PBT. Their tumor sizes ranged from 25 mm to 130 mm (median, 60 mm). A median total dose of 72.6 GyE in 22 fractions was delivered over 31 days to a target volume that encompassed both the primary hepatic lesion and the PVTT.Results: 32 patients were progression-free during a median follow-up period of 21 months (range, 2-88 months) and three patients experienced disease progression. Local progression-free survival rates were 46% at 2 years and 20% at 5 years, and the median local progression-free survival was 21month. Acute toxicity ≥ grade 3 was observed in three patients, and no patient experienced late toxicity ≥ grade 3. None of the patients had to discontinue treatment as a result of toxicity.Conclusion: PBT improved local control and significantly prolonged survival in HCC patients with PVTT

Comparisons of dose-volume histograms for proton-beam versus 3-D conformal x-ray therapy in patients with stage I non-small cell lung cancer.

PURPOSE: Dose-volume histograms (DVHs) were reviewed to determine if there is an advantage of the two modalities when treating patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 24 stage I NSCLC patients who underwent proton-beam therapy (PBT) from June 2003 to May 2007 were included in this study. Based on the same clinical target volumes (CTVs), treatment planning was made to cover CTV within 90% isodose lines. Each patient was evaluated by two sets of DVHs, one for PBT and the other for three-dimensional conformal X-ray therapy (3D-CRT). RESULTS: For all patients, the 95% isodose line covered 86.4% of the CTV for PBT, and 43.2% for 3D-CRT. PBT was associated with significantly lower mean doses to the ipsilateral lung, total lung, heart, esophagus, and spinal cord than 3D-CRT. PBT offered reduced radiation doses to the lung when evaluated in terms of percentage lung volumes receiving > or = 5 Gy (V(5)), > or = 10 Gy (V(10)), and > or = 20 Gy (V(20)) when compared to 3D-CRT. CONCLUSION: PBT is advantageous over 3D-CRT in reducing doses to the lung, heart, esophagus, and spinal cord in treating stage I NSCLC

Proton Beam Therapy for Hepatocellular Carcinoma: The University of Tsukuba Experience

BACKGROUND:: The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital-based facility at the University of Tsukuba. METHODS:: From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed. RESULTS:: Overall actuarial survival rates at 1-year, 3-years, and 5-years were 89.5% (95% confidence interval [95% CI], 85.7-93.1%), 64.7% (95% CI, 56.6-72.9%), and 44.6% (95% CI, 29.7-59.5%), respectively. Child-Pugh liver function (hazards ratio [HR], 2.84; P 125 mL (P < .05). CONCLUSIONS:: The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated

Proton Beam Therapy for Large Hepatocellular Carcinoma

PURPOSE: To investigate the safety and efficacy of proton beam therapy (PBT) in patients with large hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Twenty-two patients with HCC larger than 10 cm were treated with proton beam therapy at our institution between 1985 and 2006. Twenty-one of the 22 patients were not surgical candidates because of advanced HCC, intercurrent disease, or old age. Median tumor size was 11 cm (range, 10-14cm), and median clinical target volume was 567 cm(3) (range, 335-1,398 cm(3)). Hepatocellular carcinoma was solitary in 18 patients and multifocal in 4 patients. Tumor types were nodular and diffuse in 18 and 4 patients, respectively. Portal vein tumor thrombosis was present in 11 patients. Median total dose delivered was 72.6 GyE in 22 fractions (range, 47.3-89.1 GyE in 10-35 fractions). RESULTS: The median follow-up period was 13.4 months (range, 1.5-85 months). Tumor control rate at 2 years was 87%. One-year overall and progression-free survival rates were 64% and 62%, respectively. Two-year overall and progression-free survival rates were 36% and 24%, respectively. The predominant tumor progression pattern was new hepatic tumor development outside the irradiated field. No late treatment-related toxicity of Grade 3 or higher was observed. CONCLUSIONS: The Bragg peak properties of PBT allow for improved conformality of the treatment field. As such, large tumor volumes can be irradiated to high doses without significant dose exposure to surrounding normal tissue. Proton beam therapy therefore represents a promising modality for the treatment of large-volume HCC. Our study shows that PBT is an effective and safe method for the treatment of patients with large HCC

Gastrointestinal Malignancies

The presence of dose-limiting hepatic and renal parenchyma, as well as bowel adjacent to the tumor, have provided the rationale for use of charged particles in the treatment of gastrointestinal malignancies. The most extensive experience has been in the treatment of hepatocellular carcinomas (HCCs), but esophageal, rectal, and pancreatic lesions have also been treated. Japanese investigators have accumulated experience with both protons and carbon ions for these tumors. Experts from Tsukuba University and the National Institute of Radiological Sciences (NIRS) in Chiba have collaborated on this chapter to share their experience. One third of the 1,556 patients treated with proton beam therapy (PBT) at Tsukuba as of March 2006 had HCC. To date, approximately 2,800 patients have been treated with carbon ion beams at NIRS, 14% of whom have had gastrointestinal malignancies including HCC, pancreatic cancer, esophageal cancer, and pelvic recurrence of rectal cancer after surgery (see Table 19.1

Malignant Myoepithelioma in the Maxillary Sinus: Case Report and Review of the Literature

Malignant myoepithelioma of the head and neck usually arises in the salivary glands. We experienced a rare case with malignant myoepithelioma in the maxillary sinus. A 47-year-old woman with malignant myoepithelioma in the maxillary sinus underwent partial maxillectomy. However, local recurrence occurred 28 months after surgery and she was subsequently treated with radiation therapy with proton beams. The recurrent tumor showed complete response and the patient was alive with no evidence of disease 30 months after irradiation. No therapy-related severe toxicities were observed. A rare case with malignant myoepithelioma in the maxillary sinus was successfully treated with radiation therapy

Phase I/II Trial of Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme

PURPOSE: To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM). METHODS AND MATERIALS: Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of >/=60; (2) the diameter of the enhanced area before radiotherapy was </=40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T(2)-weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hours later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks. RESULTS: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months. CONCLUSIONS: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences