Masaharu Hata

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.

Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus

Treatment modalities for patients with hepatocellular carcinoma (HCC) who have portal vein tumor thrombus (PVTT) are limited and controversial; furthermore, the prognosis for these patients is extremely poor. The authors conducted a retrospective review to determine the role of proton beam therapy in the treatment of patients who had HCC with PVTT.

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.

Proton Therapy for Head and Neck Malignancies at Tsukuba

Purpose:To evaluate the effectiveness and feasibility of proton therapy for head and neck cancers.Patients and Methods:From 1983 to 2000, 33 patients with head and neck malignancies but no history of surgical resection were treated with 250-MeV protons with or without X-ray irradiation. This study retrospectively evaluated local control, survival, and treatment sequelae of these patients. The median total target dose using protons with or without X-rays was 76 Gy (range: 42–99 Gy) and the median proton dose per fraction 2.8 Gy (range: 1.5–6.0 Gy).Results:Overall 5-year survival and local control rates were 44% and 74%, respectively. One (3%) and six patients (18%) suffered from treatment-related acute and late toxicity > grade 3 (RTOG/EORTC acute and late radiation morbidity scoring criteria). One patient with a history of radiotherapy suffered from acute toxicity > grade 3.Conclusion:Proton therapy appeared to offer high local control rates with few toxicities relative to conventional radiotherapy. However, late toxicity was seen in areas where large radiation doses had been given.Ziel:Prüfung der Wirksamkeit und Durchführbarkeit einer Protonentherapie bei Kopf-Hals-Malignomen.Patienten und Methodik:Von 1983 bis 2000 wurden 33 Patienten mit Kopf-Hals-Malignomen, aber ohne chirurgische Vorbehandlung mit 250-MeV-Protonen mit oder ohne Röntgenstrahlung behandelt. Diese Studie wertet retrospektiv lokale Kontrolle, Überleben und Therapiefolgen aus. Die mediane Gesamtdosis bei Anwendung von Protonen mit oder ohne Röntgenstrahlung betrug 76 Gy (Spanne 42–99 Gy), und die mediane Protonenfraktionsdosis war 2,8 Gy (Spanne 1,5–6,0 Gy).Ergebnisse:Die Fünf-Jahres-Überlebens- und Lokalkontrollraten betrugen 44% bzw. 74%. 1 (3%) und 6 (18 %) Patienten litten unter therapiebedingten Akut- und Langzeitnebenwirkungen höher als Grad 3 (RTOG/EORTC-Kriterien für Akut- und Langzeitstrahlennebenwirkungen). 1 Patient mit vorausgegangener Strahlentherapie erlitt akute Nebenwirkungen höher als Grad 3.Schlussfolgerung:Die Protonentherapie führte zu hohen Raten lokaler Kontrolle bei—verglichen mit konventioneller Radiotherapie—geringen Nebenwirkungen. Allerdings wurden Langzeitnebenwirkungen in Arealen beobachtet, die hoher Strahlungsdosis ausgesetzt gewesen waren.

FDG-PET scanning after radiation can predict tumor regrowth three months later.

PURPOSE Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) is well known for providing excellent clinical information regarding malignant tumors. We investigated whether dual-time FDG-PET performed immediately post radiation could predict early regrowth of malignant tumors. MATERIALS AND METHODS Twenty patients with malignant tumors were included in this study. All patients received radiation, and each underwent FDG-PET before the initiation of therapy and within 10 days of completing their course of irradiation. PET images after irradiation were obtained at 60 min and 180 min post FDG injection. For 26 lesions in 20 patients, standardized uptake value (SUV) before and after treatment was calculated and then correlated with postradiation tumor response and outcome at 3 months status post irradiation. RESULTS Retention index [RI = (SUV on delayed image - SUV on early image)/SUV on early image] after irradiation showed a significant difference between patients with residual tumor and those without residual tumor at 3 months status post irradiation (p < 0.0025). All 9 lesions in 6 patients with residual tumors showed more than 0.1 of RI, whereas none of the lesions with less than 0.1 of RI revealed residual tumors. CONCLUSIONS Dual-time FDG-PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors.

Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer: Analysis of therapeutic results in 112 cases

PURPOSE To evaluate the therapeutic results and rate of organ preservation in patients with stage III or IV oral cancer treated with retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy. MATERIALS AND METHODS One hundred and twelve patients with stage III and IV oral squamous cell carcinoma underwent intra-arterial chemoradiotherapy. Catheterization from the superficial temporal and occipital arteries was performed. Treatment consisted of superselective intra-arterial chemotherapy (docetaxel, total 60mg/m(2), cisplatin, total 150mg/m(2)) and daily concurrent radiotherapy (total of 60Gy) for 6 weeks. RESULTS The median follow-up for all patients was 46.2 months (range, 10-76 months). After intra-arterial chemoradiotherapy, primary site complete response was achieved in 98 (87.5%) of 112 cases. Five-year survival and local control rates were 71.3% and 79.3%, respectively. Grade 3 or 4 toxicities included mucositis in 92.0%, neutropenia in 30.4%, dermatitis in 28.6%, anemia in 26.8%, and thrombocytopenia in 7.1% of patients. Grade 3 toxicities included dysphagia in 72.3%, nausea/vomiting in 21.4%, fever in 8.0%, and renal failure in 0.9% of patients. CONCLUSION Retrograde superselective intra-arterial chemotherapy and daily concurrent radiotherapy for stage III and IV oral cancer provided good overall survival and local control.

Role of Radiotherapy as Curative Treatment of Extramammary Paget’s Disease

PURPOSE Extramammary Pagets disease (EMPD) is a relatively rare malignancy that usually arises in the genital areas. Wide surgical excision remains the standard and most reliable curative treatment of EMPD. However, surgery is sometimes not possible, because many patients are elderly, and complete excision can be difficult owing to the tumor location. We, therefore, performed a review to determine the role of radiotherapy (RT) for EMPD. METHODS AND MATERIALS A total of 22 patients with EMPD in their external genitalia (4 men and 18 women, age 52-94 years at RT) underwent RT with curative intent. Nine patients had regional lymph node metastases. A total dose of 45-70.2 Gy (median, 60) was delivered to the pelvis, including the tumors, in 25-39 fractions (median, 33). RESULTS In all but 3 patients, the irradiated tumors were controlled during a follow-up period of 8-133 months (median, 42). Of the 22 patients, 13 developed recurrences, including local progression within the radiation field in 3 and lymph node and/or distant metastases outside the radiation field in 10, at 3-43 months after treatment. The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Of the 22 patients, 7 patients had died at 33-73 months after RT. The cause of death was tumor progression in 4, infectious pneumonia in 2, and renal failure in 1 patient. The overall and cause-specific survival rates were 100% for both at 2 years and 53% and 73% at 5 years, respectively. No therapy-related Grade 3 or greater toxicity was observed. CONCLUSIONS RT is safe and effective for patients with EMPD. It appears to contribute to prolonged survival as a result of good tumor control.

Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors.

It is well known that prophylactic cranial irradiation is highly effective in preventing central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL). Nevertheless, there have been very few reports on the late effects, especially pituitary function and growth, in long‐term survivors who were treated with 18 Gy cranial irradiation in childhood. The subjects consisted of 35 children with ALL who were treated with prophylactic 18 Gy cranial irradiation at Kanagawa Childrens Medical Center between October 1981 and February 1995. All patients received cranial irradiation after first attaining complete remission with induction chemotherapy, according to the treatment protocols prescribed by the Tokyo Childrens Leukemia Study Group (TCLSG) and Tokyo Childrens Cancer Study Group (TCCSG). Their ages at the time of cranial irradiation ranged from 2.2–15.0 years (mean 6.8). We evaluated their pituitary functions by measuring their pituitary hormone values 0.7–11.3 years (mean 6.0) after cranial irradiation and their growth by analyzing their height standard deviation score (SDS) at diagnosis of ALL and their final height SDS at the mean follow‐up period of 8.2 years after cranial irradiation. Height SDS is defined as the difference between the patients height and the mean height of their age and sex, divided by the standard deviation of their age and sex. Eight of 35 patients had ALL relapse, involving the bone marrow in seven patients and the CNS in only one. Six of the eight patients with relapse died 1.5–6.6 years after cranial irradiation and the other two patients were salvaged by further intensive therapies. The remaining 27 relapse‐free patients have survived for 1.4–15.8 years (mean 10.1) after cranial irradiation. Twenty‐six of the 29 survivors are long‐term survivors of more than 5 years. Although there was one patient with an abnormal result in each value of growth hormone (GH), adrenocorticotropic hormone (ACTH), and prolactin (PRL), and two patients with abnormal results in thyroid‐stimulating hormone (TSH) values, none of the patients had clinical symptoms of pituitary hormone abnormality and none required hormone supplements. The final height SDS decreased significantly compared with the height SDS at diagnosis of ALL in the long‐term survivors (P = 0.001) and the height SDS of the patients who had received cranial irradiation at a young age tended to decrease gradually (P = 0.019). However, no patient showed severe growth failure. It is considered that prophylactic 18 Gy cranial irradiation plus chemotherapy for ALL in childhood can effectively prevent CNS relapse and is unlikely to produce clinically significant late effects, although it may cause slight pituitary hormone abnormality.

Noninvasive and Curative Radiation Therapy for Sebaceous Carcinoma of the Eyelid

PURPOSE Sebaceous carcinoma of the eyelid is a rare malignancy. Surgical excision remains the standard and most reliable curative treatment. However, surgery is sometimes not possible because many patients are elderly, and it frequently causes functional and cosmetic impairment of the eyelid. We therefore carried out a study to determine the role of radiation therapy in relation to sebaceous carcinoma of the eyelid. METHODS AND MATERIALS Thirteen patients with sebaceous carcinoma of the eyelid underwent radiation therapy with curative intent. There were 6 men and 7 women, and their ages at irradiation ranged from 60 to 85 years (median, 78 years). Only 1 patient had cervical lymph node metastasis, and none of the patients had distant metastasis. A total dose of 50 to 66.6 Gy (median, 60 Gy) was delivered to tumor sites in 22 to 37 fractions. RESULTS All irradiated tumors were controlled at a median follow-up period of 55 months. Only 1 patient had recurrence of cervical lymph node metastasis outside the radiation field, at 22 months after irradiation. The 5-year local progression-free and disease-free rates were 100% and 89%, respectively. The overall and disease-free survival rates at 5 years were 100% and 89%, respectively. Although acute and transient therapy-related reactions of Grade 2 or less were observed, there were no severe toxicities of Grade 3 or greater. CONCLUSIONS Radiation therapy is a safe and effective treatment for patients with sebaceous carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.