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.

Classical tandem-source dwelling covering the entire uterus: essential in modern intracavitary radiotherapy for cervical cancer?

PURPOSE: We investigated whether conventional tandem-source dwelling to cover the entire uterus, classically regarded as the target volume, is necessary in modern intracavitary radiotherapy (ICRT) for cervical cancer. MATERIALS AND METHODS: The study included 95 cervical squamous cell carcinoma patients treated by high-dose-rate ICRT (point A dose was 6.0 Gy, with three to five insertions per patient) after external beam radiotherapy (EBRT), with central pelvic doses of 12-50 Gy. The tandem-source dwell length was adjusted to the target volume specified by magnetic resonance (MR) imaging. A tandem applicator was inserted as far as the uterine fundus in accordance with the post-EBRT MR-assessed cavity length. The pre-EBRT MR-specified target volume was used for the dwell-length adjustment. The safety of the dwell-length adjustment was assessed in terms of treatment failure. RESULTS: The dwell-length adjustment was made in 248 of 366 total insertions with a dwell-length reduction of 5-55 mm (median 15 mm) at the corpus. Pelvic failure was identified in 22 patients with a 2-year pelvic disease-free survival rate of 75.6% but without evidence of failure at dwelling-skipped corpuses. CONCLUSION: Given after pelvic EBRT and ICRT of full-length dwelling in part, which may have eradicated possible subclinical extension, adjustment of the tandem-source dwell length to the MR-specified target volume appeared to be safe.

Proton irradiation in a single fraction for hepatocellular carcinoma patients with uncontrollable ascites. Technical considerations and results.

PURPOSE: To present technical considerations and results of proton irradiation in a single fraction for hepatocellular carcinoma (HCC) patients with uncontrollable ascites. PATIENTS AND METHODS: Three HCC patients with uncontrollable ascites underwent proton irradiation of 24 Gy in a single fraction. Hepatic tumors were solitary in two patients, and multiple in one, and tumor sizes were 30, 30, and 33 mm in maximum diameter. No patient had lymph node or distant metastases. The center position of radiation fields was determined and the beam range was adjusted, using CT data taken immediately before irradiation to compensate for changes in the volume of ascites. Adjustment of the beam range was within 6 mm in water-equivalent thickness. RESULTS: All irradiated tumors showed objective responses, and were controlled during the follow-up period. Of the three patients, two were alive with no evidence of disease at 13 and 30 months, respectively, after treatment. The remaining patient died of ruptured esophageal varices 6 months after treatment. No therapy-related toxicity of grade 3 or more was observed. CONCLUSION: Proton beams were successfully adjusted immediately before irradiation. Single-dose irradiation with precisely adjusted proton beams may be tolerable for HCC patients with uncontrollable ascites.

Explanation for the failure of neoadjuvant chemotherapy to improve outcomes after radiotherapy for locally advanced uterine cervical cancer from the standpoint of the tumor regression rate.

PURPOSE: Treatment outcomes for patients with locally advanced cervical cancer are no better with neoadjuvant chemotherapy (NAC) combined with radiotherapy (RT) than with RT alone. We investigated the reason for this failure from the standpoint of the tumor regression rate (RR). MATERIALS AND METHODS: A total of 48 patients with clinical stage IIB-IVA cervical squamous cell carcinoma were treated clinically with cisplatin-based NAC plus RT (n = 15) or RT alone (n = 33). The RR was defined as the slope of a tumor shrinkage curve derived with magnetic resonance images. The local control rate (LCR) and disease-free rate (DFR) were estimated by clinical stage (IIB vs. III-IVA), pretreatment volume (< or = median vs. > median), lymph node status (negative vs. positive), treatment type, overall treatment time (< or =8 weeks vs. >8 weeks), and RR (< or = median vs. > median) using univariate and multivariate analyses. RESULTS: RR during NAC or during NAC and RT (n = 15) was not significantly higher than RR by RT alone (n = 33). Low RR and positive nodal status were significantly powerful prognostic factors for both the LCR and DFR, whereas the others were not. CONCLUSION: Although effective in reducing tumor volume prior to RT, NAC showed no overall effect in increasing the RR, which was shown to be the most powerful prognostic factor.

Proton beam therapy for hepatocellular carcinoma with inferior vena cava tumor thrombus: report of three cases.

Three patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) were treated using proton beam therapy at the University of Tsukuba, Japan. A total dose of 50-70 Gy in 10-35 fractions was given to the primary tumor and IVCTT. All the patients survived for more than 1 year from the beginning of proton beam therapy (13-55 months) and no treatment-related toxicity of grade 3 or higher was observed. These cases suggest that proton beam therapy is safe and effective for patients with HCC associated with IVCTT.

Proton beam therapy for aged patients with hepatocellular carcinoma.

PURPOSE: To investigate the safety and efficacy of proton beam therapy for aged patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Twenty-one patients aged > or =80 years with HCC underwent proton beam therapy. At the time of irradiation, patient age ranged from 80 to 85 years (median, 81 years). Hepatic tumors were solitary in 17 patients and multiple in 4. Tumor size ranged from 10 to 135 mm (median, 40 mm) in maximum diameter. Ten, 5, and 6 patients received proton beam irradiation with total doses of 60 Gy in 10 fractions, 66 Gy in 22 fractions, and 70 Gy in 35 fractions, respectively, according to tumor location. RESULTS: All irradiated tumors were controlled during the follow-up period of 6-49 months (median, 16 months). Five patients showed new hepatic tumors outside the irradiated volume, 2-13 months after treatment, and 1 of them also had lung metastasis. The local progression-free and disease-free rates were 100% and 72% at 3 years, respectively. Of 21 patients, 7 died 6-49 months after treatment; 2 patients each died of trauma and old age, and 1 patient each died of HCC, pneumonia, and arrhythmia. The 3-year overall, cause-specific, and disease-free survival rates were 62%, 88%, and 51%, respectively. No therapy-related toxicity of Grade > or = 3 but thrombocytopenia in 2 patients was observed. CONCLUSIONS: Proton beam therapy seems to be tolerable, effective, and safe for aged patients with HCC. It may contribute to prolonged survival due to tumor control.

Hypofractionated high-dose proton beam therapy for stage I non-small-cell lung cancer: preliminary results of a phase I/II clinical study.

PURPOSE: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. RESULTS: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade > or =3 was observed. CONCLUSIONS: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC.

Long-term outcome of patients with intracranial germinoma.

PURPOSE: This study was to clarify the long-term subjective functional state and the therapeutic factors that may influence the outcome and ADL of patients with intracranial germinoma. METHODS AND MATERIALS: Subjects were 19 patients with an average age of 16.5 years. All patients received radiotherapy with a mean dose of 42.8 Gy, while 14 patients also received chemotherapies. After a median follow-up of 137 months (41-271), a written questionnaire was sent to each patient. RESULTS: Estimated 5- and 10-year event-free survival rates were 78% and 71%, respectively. Recurrence occurred in 5 patients, and 1 patient died of tumor. The extent of surgery did not affect the incidence of recurrence. Chemotherapy remained adjuvant. Radiotherapy administered to the field encompassing the whole ventricle was essential for long-term tumor control. Only one patient complained of a major treatment-related complication at the time of the questionnaire: radiation-induced cavernomas. CONCLUSIONS: Adverse effects related to treatment are not significant in this study. Radiotherapy of 24 Gy to the field encompassing the whole ventricle is essential, and elective use of chemotherapy and/or additional local boost radiotherapy may prevent recurrence and maintain quality of life (QOL) of the patients for a relatively long period.

Determination of gate-on and -off timing in respiration-gated radiotherapy.

The purpose of this study was to develop an efficient method of determining gate-on and -off timing in respiration-gated radiotherapy. Gate-on and -off timing in a breathing cycle were defined as the respiratory signal level for the start of irradiation (Ls) in the expiration phase and that for the end of irradiation (Le) in the inspiration phase, respectively. Thirty subjects participated in this study. The diaphragm was used as the tracking target, and time-dependent changes in the position of the target were measured together with those in the respiratory signal level. For each subject, the following maps were created by varying the combination of Ls and Le: absolute target displacement (ATD) map, relative target displacement (RTD) map, and gate-on duty cycle (GDC) map. By classifying respiratory signal waveforms, three respiratory types were derived (A: the length of end-expiration level >40% of a breathing cycle, B: the length of end-expiration level 20% of a breathing cycle, and C: the length of end-expiration level

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.

Sequential evaluation of hepatic functional reserve by 99mTechnetium-galactosyl human serum albumin scintigraphy after proton beam therapy: a report of three cases and a review of the literatures.

The treatment strategy for malignant liver tumors should be appropriately determined because post-treatment quality of life greatly depends on the patients' residual hepatic function. In this report, we present three patients with malignant liver tumors treated by proton beam therapy in whom pre- and post-therapeutic hepatic functional reserves were evaluated sequentially for more than a year by 99mTechnetium-galactosyl human serum albumin (99mTc-GSA) scintigraphy. All three patients exhibited the distinctive time course of 99mTc-GSA uptake efficiency, which suggested a transient decline in the ratio of liver activity to heart and liver activity at 15 minutes (LHL15) 3-6 months after proton beam therapy. This change was not in parallel with that expected from a functioning normal liver tissue volume. In a year after proton beam therapy, LHL15 recovered nearly to the pre-treatment level in all three patients. Our observations may be related to the up-regulation of receptor-mediated 99mTc-GSA uptake during hepatic regeneration after proton beam therapy.

Proton beam therapy for hepatocellular carcinoma with limited treatment options.

BACKGROUND: 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. METHODS: Twenty-one patients with HCC for whom other treatment modalities either were contraindicative or were unfeasible because of coexisting diseases and unfavorable conditions received proton beam therapy. Four patients had renal failure, 2 patients had severe heart disease, 9 patients had severe cirrhosis, 1 patient had aplastic anemia, 1 patient had a dissecting abdominal aortic aneurysm before treatment, and 4 patients had bleeding tendency or unresectable tumors. Moreover, 2 of the latter 4 patients were allergic to iodine, and 2 other patients were unable to be catheterized for transcatheter arterial chemoembolization. Hepatic tumors were solitary in 14 patients and multiple in 7 patients, and the tumors ranged in greatest dimension from 25 mm to 100 mm (median, 40 mm). No patient had regional lymph node or distant metastasis. Total doses of 63 grays (Gy) to 84 Gy (median, 73 Gy) in 13 to 27 fractions (median, 18 fractions) were used for tumor treatments. RESULTS: All but 1 of the irradiated tumors were controlled at a median follow-up of 3.3 years. The objective response rate was 81%, and the primary site-control rate was 93% at 5 years. Eleven patients had intrahepatic recurrences, and 2 patients had distant metastases in the lungs. Four of 11 patients with intrahepatic recurrences received a second course of proton beam therapy, and all recurrent tumors were controlled. The overall and cause-specific survival rates were 62% and 82% at 2 years, respectively, and 33% and 67% at 5 years, respectively. Grade > or =3 therapy-related toxicities were not observed. CONCLUSIONS: Proton beam therapy was safe and effective for a variety of patients with HCC. The current results suggested that this method was tolerable and effective, even for patients with HCC who had limited treatment options.

Proton beam therapy for invasive bladder cancer: a prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy.

PURPOSE: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. METHODS AND MATERIALS: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. RESULTS: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. CONCLUSIONS: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.

Repeated proton beam therapy for hepatocellular carcinoma.

PURPOSE: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at the University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. RESULTS: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. CONCLUSIONS: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors.

PURPOSE: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. METHODS AND MATERIALS: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day(-1)) of the shrinkage curve by fitting to an exponential equation. RESULTS: Early-assessed radioresponse ranged from 0.001 to 0.106 day(-1) (median, 0.021 day(-1)) and late-assessed radioresponse from 0.009 to 0.091 day(-1) (median, 0.021 day(-1)), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R(2) = 0.714, p = 0.0005). CONCLUSIONS: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness.

Proton beam therapy for hepatocellular carcinoma with portal vein tumor thrombus.

BACKGROUND: 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. METHODS: Twelve patients with HCC who had tumor thrombus in the main trunk or major branches of the portal vein (clinical T3-T4N0M0) were treated with proton beam therapy. At the time they received proton beam irradiation, patients ranged in age from 42 years to 80 years (median, 62 years), and their tumors ranged in size from 40 mm to 110 mm (median, 60 mm) in greatest dimension. A total dose of 50-72 gray (Gy) (median, 55 Gy) in 10-22 fractions was delivered to the tumors, including PVTT. RESULTS: All tumors that were treated with proton beam therapy remained controlled at a median follow-up of 2.3 years (range, 0.3-7.3 years). Among 12 patients, 10 patients had new liver tumors outside the irradiated volume 0.1-2.4 years after proton beam therapy, and 3 patients also had distant metastases; consequently, 8 patients died of disease, and 2 patients were salvaged by further therapies. The remaining two patients were alive with no evidence of disease 4.3 years and 6.4 years after proton beam therapy. The progression-free survival rates were 67% at 2 years and 24% at 5 years. The median progression-free survival was 2.3 years. According to the Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group), therapy-related toxicity > or = Grade 3 was not observed. CONCLUSIONS: Proton beam therapy for patients with HCC who had PVTT was feasible and effective. It appeared to improve survival and local control significantly for these patients.

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.