Yasuyuki Akine

Proton Beam Therapy for Hepatocellular Carcinoma: A Retrospective Review of 162 Patients

Purpose: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. Experimental Design: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. Results: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. Conclusions: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.

Clinical evaluation of proton radiotherapy for non-small-cell lung cancer.

PURPOSE To evaluate the clinical results of proton radiotherapy for patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS Between 1983 and 2000, 51 NSCLC patients were treated with proton beams at the University of Tsukuba. There were 28 patients in Stage I, 9 in Stage II, 8 in Stage III, 1 in Stage IV, and 5 with recurrent disease. Thirty-three patients had squamous cell carcinoma, 17 had adenocarcinoma, and 1 had large-cell carcinoma. Median fraction and total doses given were 3.0 Gy (range 2.0-6.0 Gy), and 76.0 Gy (range 49.0-93.0 Gy), respectively. RESULTS The 5-year overall survival rate was 29% for all patients, 70% for 9 Stage IA patients, and 16% for 19 Stage IB patients, respectively (IA vs. IB: p < 0.05). The 5-year in-field local control rate was higher in patients with Stage IA (89%) when compared with those with Stage IB (39%). Forty-seven patients (92%) experienced acute lung toxicity of Grade 1 or less; 3 had Grade 2, 1 had Grade 3, and none experienced Grade 4 or higher. Patients in the present series showed very little late toxicity. CONCLUSIONS Proton therapy is a very safe and effective treatment for patients with NSCLC, especially for those with early stages. The relative merit of proton therapy in comparison with stereotactic photon radiotherapy or three-dimensional conformal photon radiotherapy remains to be defined through future clinical trials.

Radiotherapy for hepatocellular carcinoma: An overview

Division of Radiation Oncology, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 097, Houston, Texas 77030, United States Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea Department of Radiation Oncology, University of Tsukuba, Tsukuba, Japan Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Lyon Pierre Benite, France

High-dose-rate intracavitary irradiation in the treatment of carcinoma of the uterine cervix: Early experience with 84 patients☆

Eighty-four patients with previously untreated invasive carcinoma of the uterine cervix were treated by high-dose-rate intracavitary irradiation using a remotely controlled afterloading system (Ralstron) with or without external irradiation at the National Cancer Center Hospital, Tokyo, between 1977 and 1981. Survival rates and local control rates were comparable to those for 372 patients treated by low-dose-rate intracavitary irradiation with or without external irradiation from 1972 to 1981 at the hospital. The incidence of major complications was 5.1 and 2.4% for the patients treated by low-dose-rate intracavitary irradiation and by high-dose-rate irradiation, respectively. The results are comparable to those reported by other institutions. We have abandoned the conventional low-dose-rate intracavitary irradiation with the impression that the high-dose-rate remotely controlled afterloading system is a good alternative to the conventional one.

Radiotherapy of T1 glottic cancer with 6 MeV X rays.

We treated 154 patients with T1 glottic carcinoma with 6 MeV X rays through 16 cm2 parallel-opposing open fields on a free set-up delivering a median dose of 67 Gy in 6 2/3 weeks. Observed and relative 5-year survival rates for all patients were 87% and 100%, respectively. The local control rate at 5 years was 89%. Of 18 patients who clinically had local recurrence, 17 were salvaged by a secondary treatment. There were no complications requiring medical or surgical attention. A tendency toward increasing local control rates with increasing total doses was observed in the range between 57.5 Gy and 72.5. No significant correlation was found between local control rates and field size, daily dose, or the technique used. A tendency toward a lower local control rate was noted for patients whose anterior commissures were grossly involved; however, it is not known if this could be attributed to the use of 6 MeV X rays. The results are comparable to those obtained with 60Co as reported in the literature. It is concluded that 6 MeV X rays on a free set-up delivering 65-70 Gy in 6 1/2-7 weeks can be used satisfactorily for the treatment of early glottic carcinoma.

FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR CHOROIDAL MELANOMA

Stereotactic radiotherapy used for the treatment of choroidal melanoma made use of a 6-MeV linac with built-in multileaf collimators and a simple plastic head mold. The latter provided excellent head and ocular immobilization. The system resulted in highly localized dose distributions with a maximum 2-mm targeting error during fractionated treatments. Based on these techniques, sixteen patients with choroidal melanoma have so far been treated. Majority of patients received a total dose of 48 Gy in 8 fractions. Fourteen patients who presented with small- to moderate-sized tumors have remained free of relapse or major complications during the follow-up period of 3-42 months. Two patients who presented with an extensive tumor eventually required enucleation after irradiation. Technical precision required for stereotactic radiotherapy and reproducibility for fractionation appear adequate. Encouraging preliminary results justify further studies to evaluate its efficacy as an alternative to other conventional therapeutic approaches.

Proton beam therapy for hepatocellular carcinoma with limited treatment options

The authors conducted a retrospective review to define the usefulness of proton beam therapy for patients who had hepatocellular carcinoma (HCC) with limited treatment options.

Proton Beam Therapy for Hepatocellular Carcinoma Patients with Severe Cirrhosis

Background and Purpose:Hepatocellular carcinoma (HCC) patients with severe cirrhosis are usually treated with supportive care because of their poor prognosis. However, the survival of severe cirrhotic patients has recently improved due to advanced treatments. The aim of this study was to define the role of proton beam therapy for HCC patients with severe cirrhosis.Patients and Methods:19 HCC patients with Child-Pugh class C cirrhosis received proton beam therapy. The hepatic tumors were solitary in 14 patients and multiple in five, and the tumor size was 25–80 mm (median 40 mm) in maximum diameter. No patient had regional lymph node or distant metastasis. Total doses of 50–84 Gy (median 72 Gy) in ten to 24 fractions (median 16) were delivered to the tumors.Results:Of the 19 patients, six, eight and four died of cancer, liver failure and intercurrent diseases, respectively, during the follow-up period of 3–63 months (median 17 months) after treatment. A remaining patient was alive with no evidence of disease 33 months after treatment. All but one of irradiated tumors were controlled during the follow-up period. Ten patients had new intrahepatic tumors outside the irradiated volume. The overall and progression-free survival rates were 53% and 47% at 1 year, respectively, and 42% each at 2 years. Performance status and Child-Pugh score were significant prognostic factors for survival. Therapy-related toxicity of grade 3 or more was not observed.Conclusion:Proton beam therapy for HCC patients with severe cirrhosis was tolerable. It may improve survival for patients with relatively good general condition and liver function.Hintergrund und Ziel:Patienten mit Leberzellkarzinom (HCC [„hepatocellular carcinoma“]) und schwerer Zirrhose werden aufgrund der schlechten Prognose gewöhnlich konservativ behandelt. Allerdings haben fortschrittliche Therapien in letzter Zeit zu einer Verbesserung der Überlebenszeit von Patienten mit schwerer Zirrhose geführt. Das Ziel der vorliegenden Studie war die Bestimmung der Rolle einer Protonentherapie für HCC-Patienten mit schwerer Zirrhose.Patienten und Methodik:19 HCC-Patienten mit Zirrhose der Child-Pugh-Klasse C wurden mit Protonenstrahlen behandelt. 14 Patienten wiesen einzelne und fünf Patienten multiple Lebertumoren auf. Hinsichtlich der Tumorgröße variierte der maximale Durchmesser dabei zwischen 25 und 80 mm (durchschnittlich 40 mm). Keiner der Patienten hatte regionäre Lymphknoten- oder Fernmetastasen in regionären oder entfernten Lymphknoten. Die Gesamtstrahlendosis betrug 50–84 Gy (durchschnittlich 72 Gy) und wurde in zehn bis 24 Fraktionen (durchschnittlich 16 Fraktionen) verabreicht.Ergebnisse:Im Nachuntersuchungszeitraum von 3–63 Monaten (durchschnittlich 17 Monate) verstarben sechs der insgesamt 19 Patienten an Krebs, acht an Leberversagen und vier an interkurrierenden Erkrankungen. Ein Patient war 33 Monate nach der Behandlung ohne Krankheitszeichen am Leben. Mit einer Ausnahme wurden alle Tumoren während der Nachuntersuchung mit entsprechenden Kontrollen verglichen. Zehn Patienten hatten intrahepatische Tumoren, die außerhalb des bestrahlten Bereichs lagen. Die Gesamt- und die progressionsfreie Überlebensrate betrugen nach 1 Jahr 53% und 47% und nach 2 Jahren 42%. Der Performance-Status und die Child-Pugh-Bewertung waren wichtige prognostische Faktoren für das Überleben.Schlussfolgerung:Die Protonentherapie war für Patienten mit Leberzellkarzinom und schwerer Zirrhose tolerabel. Die Behandlung könnte das Überleben von Patienten mit relativ gutem Allgemeinzustand und guter Leberfunktion verbessern.

Long-term results of proton beam therapy for carcinoma of the uterine cervix

PURPOSE To determine the role of proton therapy in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS Between 1983 and 1991, 25 patients with squamous cell carcinoma of the uterine cervix (stages IIB-IVA) were treated with a curative intent by external photon irradiation to the pelvis, followed by proton irradiation to the primary tumor, delivering a median total tumor dose of 86 Gy (range 71 Gy/26 Fr-101 Gy/46 Fr), and were followed for a median period of 139 months (range 11-184 months). RESULTS Ten-year overall survival rates for stages IIB and IIIB/IVA patients were 89% and 40%, respectively. Five-year local control rates for stages IIB and IIIB/IVA patients were 100% and 61%, respectively. Four percent of patients experienced severe (Grade 4 or more) late complications in the intestine or urinary bladder at 5 years. CONCLUSION External photon and proton therapy is effective for those who are not eligible for intracavitary irradiation, and who otherwise have a poor prognosis. The results show that tumor control, survival, and morbidity are similar to those after conventional therapy.

RADIOTHERAPY OF BRAIN METASTASES

The effect of radiotherapy in 254 cases of brain metastases, treated between 1977 and 1984, were studied. The cases included 141 of lung cancer, 28 of mammary cancer, and 85 of other primary sites. The percentages of patients with improvement in clinical symptoms were 8, 39, and 66, respectively. These were groups of patients irradiated with less than 30 Gy, 30 Gy to 50 Gy, and more than 50 Gy. The 50% survival periods from the start of irradiation for the last group were as follows: for radiotherapy only, 4.1 months, radiotherapy and surgery, 4.2 months, radiotherapy and chemotherapy combined, 6.9 months, radiotherapy, surgery and chemotherapy combined, 12.1 months. The intervals between the initial diagnosis and brain metastases were different in lung cancer and mammary cancer, but the prognosis after brain metastases showed little difference between them.