Thoracic radiotherapy for mediastinal nodal recurrence.

Radiotherapy has been used to treat loco-regional recurrences located at various intra-thoracic sites, but long-term survival of these patients has been rarely observed. We report herein a lung adenocarcinoma patient with locoregional recurrence, who was successfully treated with high-dose radiotherapy. The patient could survive with no evidence of recurrence 5 years after thoracic irradiation. It is probably safe to administrate high-dose radiotherapy for some loco-regional recurrent patients with favorable prognostic factors such as good PS, no body weight loss. Further studies will be required to define a favorable subset of patients most likely to benefit from an aggressive approach.

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.

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.

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 results of proton beam therapy for cancer of the esophagus.

PURPOSE: To present the results of proton beam therapy for patients with esophageal cancer. METHODS AND MATERIALS: This study reviewed 46 patients with esophageal cancer who were treated between 1985 and 1998 using proton beams with or without X-rays. All patients had locoregionally confined disease; all but one had squamous cell carcinoma. Of the 46 patients, 40 received combinations of X-rays (median, 48 Gy) and protons (median, 31.7 Gy) as a boost. The median total dose of combined X-ray and proton radiation for the 40 patients was 76.0 Gy (range, 69.1-87.4 Gy). The remaining 6 patients received only proton beam therapy (median, 82.0 Gy; range, 75-89.5 Gy). RESULTS: The 5-year actuarial survival rate for the 46 patients, patients with T1 (n = 23), and those with T2-T4 (n = 23) was 34%, 55%, and 13%, respectively. The 5-year disease-specific survival rate for the 46 patients, those with T1, and those with T2-T4 was 67%, 95%, and 33%, respectively. The 5-year local control rate for patients with T1 and T2-T4 lesions was 83% and 29%, respectively. The site of the first relapse was locoregional for 16 patients and distant organs for 2 patients. CONCLUSION: The results suggest that proton beam therapy is an effective treatment for patients with locally confined esophageal cancer. Additional studies are required to determine the optimal total dose, fractionation schedule, and best combinations of protons and conventional X-rays with or without chemotherapy.

Preliminary estimation of treatment effect on uterine cervical squamous cell carcinoma in terms of tumor regression rate: comparison between chemoradiotherapy and radiotherapy alone.

PURPOSE: We preliminarily estimated the treatment effect on cervical cancer in terms of the tumor regression rate (TRR) achieved with chemoradiotherapy and radiotherapy alone. MATERIALS AND METHODS: The study included cervical squamous cell carcinomas treated by radiotherapy alone (n=45) or chemoradiotherapy (concurrent once-a-week cisplatin 30 mg/m2, n=13). Tumors were measured three-dimensionally on pre- and mid-treatment magnetic resonance images. TRR was defined as the slope of the exponential regression curve of tumor volume (day(-1)) on the assumption that tumors regressed exponentially with time. RESULTS: TRR ranged widely (0.004-0.090 day-(-1)) and did not significantly differ between treatment with chemoradiotherapy (median, 0.032 day(-1)) and with radiotherapy alone (median, 0.024 day(-1)) (p = 0.361). TRR > 0.05 day(-1) was seen in four chemoradiotherapy tumors (30.8%) and in six radiotherapy-alone tumors (15.0%) (p = 0.207), whereas TRR < 0.01 day(-1) was seen in no chemoradiotherapy tumors (0.0%) and in five radiotherapy-alone tumors (11.1%) (p = 0.180). TRR for tumors > 5.0 cm in diameter was greater with chemoradiotherapy (n=5) than with radiotherapy alone (n=12) (p = 0.065). CONCLUSION: Although the difference did not reach a statistically significant level, our TRR data suggest that concurrent chemotherapy heightens the radioresponse of large-size cervical cancer.

Correlation between the respiratory waveform measured using a respiratory sensor and 3D tumor motion in gated radiotherapy.

PURPOSE: The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion. METHODS AND MATERIALS: A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function. RESULTS: The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy. CONCLUSION: Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use.

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.

Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull.

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) using noninvasive fixation of the skull on solitary or oligo brain metastatic patients as an alternative to stereotactic radiosurgery (SRS) using invasive fixation. PATIENTS AND METHODS: The subjects were 87 patients who had 4 or fewer brain metastases (50 solitary, 37 oligometastases). Treatment was conducted on 159 metastases by using a linac-based stereotactic system. The median isocentric dose was 35 Gy in 4 fractions. Whole-brain irradiation was not applied as an initial treatment. For the salvage treatment of metachronous brain metastases, repeat HSRT or whole-brain irradiation was applied. RESULTS: The actuarial 1-year local tumor control rate was 81%. Treatment-related complications were observed in 4 patients in the early period (<3 months) and in 2 patients in the late period. The median survival period was 8.7 months. Metachronous brain metastases occurred in 30 patients, and none of the 18 patients who were eligible for salvage HSRT refused to receive it again. CONCLUSIONS: Hypofractionated stereotactic radiotherapy achieved tumor control and survival equivalent to those of SRS reported in the literature. The results suggested that HSRT could be an alternative for solitary or oligo brain metastatic patients with less toxicity and less invasiveness compared to SRS.

Calculation of rotational setup error using the real-time tracking radiation therapy (RTRT) system and its application to the treatment of spinal schwannoma.

PURPOSE: The efficacy of a prototypic fluoroscopic real-time tracking radiation therapy (RTRT) system using three gold markers (2 mm in diameter) for estimating translational error, rotational setup error, and the dose to normal structures was tested in 5 patients with spinal schwannoma and a phantom. METHODS AND MATERIALS: Translational error was calculated by comparing the actual position of the marker closest to the tumor to its planned position, and the rotational setup error was calculated using the three markers around the target. Theoretically, the actual coordinates can be adjusted to the planning coordinates by sequential rotation of gamma degrees around the z axis, beta degrees around the y axis, and alpha degrees around the x axis, in this order. We measured the accuracy of the rotational calculation using a phantom. Five patients with spinal schwannoma located at a minimum of 1-5 mm from the spinal cord were treated with RTRT. Three markers were inserted percutaneously into the paravertebral deep muscle in 3 patients and surgically into two consecutive vertebral bones in two other patients. RESULTS: In the phantom study, the discrepancies between the actual and calculated rotational error were -0.1 +/- 0.5 degrees. The random error of rotation was 5.9, 4.6, and 3.1 degrees for alpha, beta, and gamma, respectively. The systematic error was 7.1, 6.6, and 3.0 degrees for alpha, beta, and gamma, respectively. The mean rotational setup error (0.2 +/- 2.2, -1.3 +/- 2.9, and -1.3 +/- 1.7 degrees for alpha, beta, and gamma, respectively) in 2 patients for whom surgical marker implantation was used was significantly smaller than that in 3 patients for whom percutaneous insertion was used (6.0 +/- 8.2, 2.7 +/- 5.9, and -2.1 +/- 4.6 degrees for alpha, beta, and gamma). Random translational setup error was significantly reduced by the RTRT setup (p < 0.0001). Systematic setup error was significantly reduced by the RTRT setup only in patients who received surgical implantation of the marker (p < 0.0001). The maximum dose to the spinal cord was estimated to be 40.6-50.3 Gy after consideration of the rotational setup error, vs. a planned maximum dose of 22.4-51.6 Gy. CONCLUSION: The RTRT system employing three internal fiducial markers is useful to reduce translational setup error and to estimate the dose to the normal structures in consideration of the rotational setup error. Surgical implantation of the marker to the vertebral bone was shown to be sufficiently rigid for the calculation of the rotational setup error. Fractionated radiotherapy for spinal schwannoma using the RTRT system may well be an alternative or supplement to surgical treatment.

Effect of treatment time on outcome of radiotherapy for oral tongue carcinoma.

PURPOSE: To investigate the importance of total treatment time on the outcome of external beam radiotherapy (EBRT) followed by internal brachytherapy for the treatment of oral tongue carcinoma. METHODS AND MATERIALS: Ninety-four patients with T1-T2N0 squamous cell carcinoma of the oral tongue were treated using 35-40 Gy EBRT followed by 35-40 Gy interstitial (137)Cs brachytherapy between 1985 and 1995. The interval between the end of EBRT and the start of interstitial treatment varied for numerous unavoidable reasons, with a mean of 25.3 days and standard deviation of 3.5 days. The median follow-up period was 59.1 months (range 6-146). RESULTS: The actuarial survival rate of all cases was 78.4% at 5 years. The 5-year local control rate for those with T1 and T2 was 92.8% and 62.7%, respectively (p < 0.05). The local control rate of the primary tumor in patients with a total treatment time >43 days was statistically lower than that of patients with a total treatment time < or =43 days in all patients (p < 0.05) and in the subgroup of Stage T2 patients (p < 0.05). Multivariate analysis revealed that the local control rates in all cases were significantly related to the T stage (T2 or not), total treatment time (>43 days or not), and location of disease (posterior or not). Regression analysis for 5-year local control as a function of treatment duration showed a 2% loss of local control per day of treatment extension >30 days (r = 0.94, p < 0.01). CONCLUSION: The total treatment time was associated with the local control rate in the RT of oral tongue carcinoma. The loss in local control was estimated to be 2.0% per additional day in our series for oral tongue carcinoma.

Clinical results of proton beam therapy for skull base chordoma.

PURPOSE: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. METHODS AND MATERIALS: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). RESULTS: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. CONCLUSION: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy.

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.

Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patterns of treatment failure.

PURPOSE: Lymph node metastasis is a major prognostic factor in the treatment of cervical cancer, but its nonsurgical assessment is not necessarily accurate, particularly in small nodes. We evaluated whether node-negative status could be accurately assessed using a low cutoff measure. METHODS AND MATERIALS: The subjects were 84 patients with Stage IIB-IVA cervical squamous cell carcinoma treated by definitive radiotherapy. Nodal status was assessed by CT as negative (<5 mm), possibly positive (5-10 mm), or probably positive (>10 mm). Cause-specific survival and the disease-free rate, including the pelvic recurrence-free and distant metastasis-free rates, were estimated. RESULTS: The cause-specific survival, disease-free rate, and pelvic recurrence-free rate at 5 years were significantly higher for the 32 patients with node-negative disease (83.5%, 86.1%, and 86.1%) and the 17 patients with possibly node-positive disease (59.2%, 93.8%, and 93.8%) than for the 35 patients with probably node-positive disease (32.6%, 22.0%, and 46.8%), respectively. No significant difference was found between negative and possibly node-positive status. In contrast, the distant metastasis-free rate differed significantly among node-negative (96.4%), possibly node-positive (59.3%), and probably node-positive (35.1%) status. CONCLUSION: Node-negative status assessed using a strict cutoff measure may be useful as a strong predictor of cervical cancer being confined to the pelvis.

Retrospective comparison of clinical outcome between radiotherapy alone and surgery plus postoperative radiotherapy in the treatment of stages IB-IIB cervical squamous cell carcinoma.

PURPOSE: To determine retrospectively whether radical surgery plus postoperative radiotherapy (RT) is superior to definitive RT from the standpoint of disease control and adverse events in the treatment of stages IB-IIA and stage IIB cervical squamous cell carcinoma. MATERIALS AND METHODS: The study included 143 patients treated by definitive RT (stages IB-IIA, n = 15; stage IIB, n = 27) or postoperative RT (stages IB-IIA, n = 67; stage IIB, n = 34). Cause-specific survival (CSS) and recurrence-free rate (RFR) were estimated. Late adverse events (proctitis, cystitis, lymphedema, and ileus) were graded, and the incidences were estimated. RESULTS: Overall, 5-year CSS and RFR did not differ significantly between patients treated with definitive RT (80.4% and 69.7%, respectively) and those treated with postoperative RT (80.6% and 79.1%, respectively). Rates according to clinical stage also did not differ significantly between the two types of treatment. Grades 1-3 adverse events occurred. Grades 2-3 lymphedema and Grades 2-3 ileus, but not Grades 2-3 cystitis, occurred significantly often with postoperative RT. CONCLUSION: Despite no difference in survival or patterns of recurrence, adverse events were significantly more frequent with postoperative RT than with definitive RT for both stages IB-IIA and stage IIB disease.

Carbon ion radiotherapy for unresectable retroperitoneal sarcomas.

PURPOSE: To evaluate the applicability of carbon ion radiotherapy (CIRT) for unresectable retroperitoneal sarcomas with regard to normal tissue morbidity and local tumor control. METHODS AND MATERIALS: From May 1997 to February 2006, 24 patients (17 male and 7 female) with unresectable retroperitoneal sarcoma received CIRT. Age ranged from 16 to 77 years (median, 48.6 years). Of the patients, 16 had primary disease and 8 recurrent disease. Histologic diagnoses were as follows: malignant fibrous histiocytoma in 6, liposarcoma in 3, malignant peripheral nerve sheath tumor in 3, Ewing/primitive neuroectodermal tumor (PNET) in 2, and miscellaneous in 10 patients. The histologic grades were as follows: Grade 3 in 15, Grade 2-3 in 2, Grade 2 in 3, and unknown in 4. Clinical target volumes ranged between 57 cm(3) and 1,194 cm(3) (median 525 cm(3)). The delivered carbon ion dose ranged from 52.8 to 73.6 GyE in 16 fixed fractions over 4 weeks. RESULTS: The median follow-up was 36 months (range, 6-143 months). The overall survival rates at 2 and 5 years were 75% and 50%, respectively. The local control rates at 2 and 5 years were 77% and 69%. No complications of the gastrointestinal tract were encountered. No other toxicity greater than Grade 2 was observed. CONCLUSIONS: Use of CIRT is suggested to be effective and safe for retroperitoneal sarcomas. The results obtained with CIRT were a good overall survival rate and local control, notwithstanding the fact that most patients were not eligible for surgical resection and had high-grade sarcomas.

Clinical Results of Carbon Ion Radiotherapy at NIRS.

In 1994 a Phase I/II clinical study on carbon ion radiotherapy was begun at NIRS using HIMAC, which was then the world's only heavy ion accelerator complex dedicated to medical use in a hospital environment. Among several types of ion species, we have chosen carbon ions for cancer therapy because they had the most optimal properties in terms of possessing, both physically and biologically, the most effective dose-localization in the body. The purpose of the clinical study was to investigate the efficacy of carbon ion radiotherapy against a variety of tumors as well as to develop effective techniques for delivering an efficient dose to the tumor. The RBE of carbon ions was estimated to be 2.0 to 3.0 along the SOBP for acute skin reactions. As of August 2006, a total of 2,867 patients had been entered into Phase I/II or Phase II studies and analyzed for toxicity and local tumor response. The results have shown that carbon ion radiotherapy has the potential ability to provide a sufficient dose to the tumor with acceptable morbidity in the surrounding normal tissues. Tumors that appear to respond favorably to carbon ions include locally advanced tumors and those with histologically non-squamous cell type of tumors such as adenocarcinoma, adenoid cystic carcinoma, malignant melanoma, hepatoma, and bone/soft tissue sarcoma. By taking advantage of the biological and physical properties of high-LET radiation, the efficacy of treatment regimens with small fractions in short treatment times has been confirmed for almost all types of tumors in carbon ion radiotherapy.

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.

Efficacy of intense screening and treatment for synchronous second primary cancers in patients with esophageal cancer.

BACKGROUND: The optimum management of esophageal cancers with synchronous second primary cancer (SPC) has not been determined. The aim of this study was to evaluate the efficacy of intense screening and treatment for esophageal cancers with synchronous SPC. METHODS: Between 1981 and 1997, 1479 patients with esophageal cancers were screened for synchronous SPC during the process of initial staging. Radical treatment was recommended for esophageal cancer and synchronous SPC in cases for whom both cancers were curable. Treatment results for esophageal cancer patients with or without synchronous SPC were compared. RESULTS: Among 1479 patients, 155 (10.5%) were found to have 166 synchronous SPC. Primary sites included the stomach in 65, the head and neck in 44, the colon/rectum in 27, the lung in 14 and other sites in 16 patients. Clinical stages of synchronous SPC were stage I in 41%, stage II in 20%, stage III in 25% and stage IV in 14%. The 5-year overall survival rates by clinical stages of esophageal cancers (stage 0, I, II, III, IV) in patients with synchronous SPC were 51% (95% CI, 23-78%), 43% (95% CI, 18-68%), 11% (95% CI, 0-22%), 14% (95% CI, 0-28%) and 12% (95% CI, 1-22%), respectively. The 5-year overall survival rate for patients with or without synchronous SPC were 20% (95% CI, 13-28%) and 32% (95% CI, 29-35%), respectively. No significant difference was observed between both groups (p = 0.2562). CONCLUSIONS: Intense screening and treatment may be justifiable in the light of the high detection rate of curable SPC and the reasonable survival of patients with synchronous SPC. However, a prospective study including cost-benefit analysis is needed to provide the evidence to justify the intense screening and treatment.