Evaluation of Delivered Doses in Proton Beam Therapy for Prostate Cancer Using Positron Emission Tomography/Computed Tomography Imaging.

AIMS: Proton beams deposit energy along their paths and stop abruptly without penetrating the opposite side, making it difficult to detect their actual paths. However, confirming the path may lead to evaluating the actual doses to organs at risk in proton therapy for prostate cancer. As proton beams produce positron emitters through nuclear fragmentation reactions, theoretically, proton beam paths can be measured by positron emission tomography/computed tomography (PET/CT). Therefore, this study investigated whether conducting PET/CT examinations immediately after proton beam therapy helps to assess the doses delivered to the rectal and urinary bladder walls, which are the major sites of radiation-related toxicity. MATERIALS AND METHODS: Between June 2022 and June 2023, 51 consecutive patients with prostate cancer who underwent proton beam therapy were enrolled and imaged with PET/CT to measure these radioactive particles and validate the actual dose delivered to the rectal and urinary bladder walls. RESULTS: The delivered doses assessed using PET/CT after proton beam therapy strongly correlated with the planned volume for proton beam treatment. CONCLUSIONS: PET/CT exhibited potential as a valuable tool for validating the irradiated dose to organs at risk.

Patients with severe emphysema have a low risk of radiation pneumonitis following stereotactic body radiotherapy.

OBJECTIVE: To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema. METHODS: This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75 Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49-90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard's criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT. RESULTS: On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p = 0.01), mild emphysema (p = 0.04) and no underlying lung disease (p = 0.01). CONCLUSION: Patients with severe emphysema had a low risk of RP following SBRT. ADVANCES IN KNOWLEDGE: Little is known about the association between RP and pulmonary emphysema. Patients with severe emphysema had lower risk of RP than those with no underlying lung disease.

Dosimetric evaluation of compensator intensity modulation-based stereotactic body radiotherapy for Stage I non-small-cell lung cancer.

OBJECTIVE: To evaluate the dosimetry of compensator intensity modulation-based stereotactic body radiotherapy (SBRT) [non-coplanar intensity-modulated radiotherapy (ncIMRT)], its use was compared with that of three-dimensional conformation-based SBRT, for patients with Stage I non-small-cell lung cancer (NSCLC). METHODS: 21 consecutive patients with Stage I NSCLC were treated with ncIMRT or SBRT at Tokyo Medical University. To compare the two techniques, ncIMRT and SBRT plans for each patient were generated, where the planning target volume (PTV) coverages were adjusted to be equivalent to each other. The prescribed dose was set as 75 Gy in 30 fractions. PTV coverage, conformity index, conformation number (CN) and homogeneity index (HI) were used to compare the two strategies. RESULTS: There was no statistically significant difference between PTV coverage for the 100%, 95% and 90% dose levels in the SBRT plan and those in the ncIMRT plan. The CN values were 0.53 ± 0.13 in the SBRT plan and 0.72 ± 0.10 in the ncIMRT plan. These values were significantly better than those of the SBRT plan (p < 0.001). The HI in the ncIMRT plan was 1.04 ± 0.03%, which was also significantly better than that of SBRT. CONCLUSION: The ncIMRT plan provided superior conformity and reduced the doses to the lung for patients with Stage I NSCLC. ADVANCES IN KNOWLEDGE: The delivery technique with compensator intensity modulation-based SBRT was evaluated. Concerning target motion, this is thought to be more robust and safer than SBRT for early-stage NSCLC.

The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with locally advanced prostatic carcinoma.

PURPOSE: To analyze the results in patients with locally advanced prostatic carcinoma treated by hormonal therapy followed by external radiotherapy using three-dimensional conformal radiation therapy (3D-CRT) boost. METHODS AND MATERIALS: From 1987 to 1995, 46 patients with histologically proven locally advanced adenocarcinoma of the prostate were treated with 3D-CRT at the National Cancer Center Hospital, Tokyo. The neoadjuvant androgen suppression started immediately after the diagnosis followed by radical radiation therapy, according to the prospective protocol. They were treated with photons of 6-14 MV for wide fields and the boost, of which a multiple-leaf collimator of 2-cm width was available. The boosted dose was delivered with the rotational 3D-CRT, after the delivery of whole pelvis 4-field box from a dose of 40-46 Gy up to 66 Gy. The planning target volume encompassed 1 cm outside throughout the clinical target volume, and the prostate and the seminal vesicles were included in the boost field. RESULTS: The 3D-CRT boost treatment completed as planned in all 46 patients. The median follow-up for all the patients was 60 months (range, 5-120 months). Nineteen of 46 patients died. Of these, 11 patients died of the intercurrent diseases. For all 46 patients, the 5- and 8-year overall survival rates were 61.3% and 42.4%, and the 5- and 8-year cause-specific survival rates were 82.4% and 64.4%, respectively. The prostate-specific antigen (PSA) relapse-free rates for 5- and 8-year were 64.6% and 52.5%, and the clinical local control rates for 5 and 8 years were 75.3% and 69.9%, respectively. The preradiation therapy PSA and the Gleason score were the factors that significantly associated with PSA relapse-free survival. Sixteen of 46 patients (35%) showed at least one form of late toxicities. Of these, 3 patients experienced late complications of Grade 3 (urinary, 2, proctitis, 1). CONCLUSION: The treatment results were fairly good and were consistent with those in Western countries, indicating that this study shows the preliminary status of 3D-CRT for the locally advanced prostate cancer in Japan. Preradiation therapy PSA seems to be a significant predictor of PSA relapse-free survival (p = 0.004) after neoadjuvant androgen suppression.

Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis.

PURPOSE: To retrospectively evaluate the risk factors for acute radiation pneumonitis (RP) and long-term prognosis of patients with lung cancer treated by thoracic radiotherapy. METHODS AND MATERIALS: Of the 256 lung cancer patients who underwent definitive thoracic radiotherapy between June 1988 and May 1998, the 191 patients who were capable of being evaluated were divided into three groups according to the grade of RP. RP was defined as "severe," when it caused severe clinical symptoms, such as intractable cough, dyspnea at rest, and the need for oxygen or steroid therapy. The definition was made by using a modification of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer acute radiation morbidity scoring criteria. Factors that influenced the incidence of severe RP were assessed by using the Mantel-Haenszel chi(2) test in the univariate analysis and the logistic regression test in the multivariate analysis. Survival rates was calculated by using the Kaplan-Meier method, and the p values indicating the significance of differences between the RP groups were calculated by the log-rank test. RESULTS: Of the 94 patients (49%) who experienced clinical RP in this study, the RP was mild in 69 (36%) and severe in 25 (13%) patients. The 3-year survival rates of the patients who experienced no, mild, and severe RP were 33.4%, 38.2%, and and 0%, respectively, and the survival rate of the patients who experienced severe RP was significantly poorer than the other two groups combined (p = 0.0028). The incidence of severe RP did not correlate with any of the baseline patient characteristics, radiotherapeutic factors, or chemotherapeutic variables. Two clinical risk factors were identified from medical records before radiotherapy: low PaO2 (< 80 torr) and high C-reactive protein (CRP) (> 1.0 ng/mL). Both of them were significantly related to the development of severe RP in the univariate analysis (p = 0.004 and 0.013, respectively), and low PaO2 remained a significant risk factor in the multivariate analysis (p = 0.034). Multivariate analysis also revealed the occurrence of severe RP to be the most important factor determining poor survival (p = 0.0065). There was no significant difference in survival rate according to whether the patients had been treated with corticosteroids. CONCLUSION: Mild and severe RP occurred in 69 (36%) and 25 (13%), respectively, of 191 lung cancer patients who had undergone irradiation of the chest. Only severe RP was an adverse prognostic factor. Low PaO2 (< 80 torr) before radiotherapy was a significant risk factor predictive of severe RP. The role of corticosteroids in RP could not be accurately determined.

Fractionated stereotactic radiotherapy of brain metastases from renal cell carcinoma.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) for brain metastases from renal cell carcinoma (RCC). METHODS AND MATERIALS: From May 1983 to September 1998, 35 patients with brain metastases from RCC underwent radiotherapy at the National Cancer Center Hospital, Tokyo; 10 patients treated initially with FSRT (FSRT group); 11 with surgery followed by conventional radiotherapy (S/CR group); and 14 with conventional radiotherapy (CR group). Survival and local control rates were determined for patients who had an ECOG performance status of 0-2. RESULTS: Overall median survival rate was 18 months, and actuarial 1- and 2-year survival rates were 57.6% and 31.0%, respectively. Median survival rates were 25.6 months for the FSRT group, 18.7 months for the S/CR group, and 4.3 months for the CR group. Significant prognostic factors associated with survival were age less than 60 years and good performance status. In patients treated with FSRT, imaging studies revealed that 21 of 24 tumors (88%) were locally controlled during a median follow-up time of 5.2 months (range 0.5-68). Actuarial 1- and 2-year local control rates were 89.6% and 55.2%, respectively. No patient suffered from acute or late complications during and following FSRT. CONCLUSIONS: FSRT offers better tumor control and prolonged survival over the S/CR or CR groups, and should be considered as primary treatment for brain metastases from RCC. Patients under 60-years-old and those with a good performance status at the beginning of radiotherapy had a better prognosis.

Reirradiation of brain and skull base tumors with fractionated stereotactic radiotherapy.

PURPOSE: We evaluated the feasibility of fractionated stereotactic radiotherapy for small intracranial recurrences after conventional radiotherapy. METHODS AND MATERIALS: Nineteen patients who had initially undergone conventional radiotherapy to intracranial lesions, receiving a median total dose of 50 Gy in 5 weeks, were retreated with stereotactic radiotherapy for their recurrences and received a median total dose of 42 Gy in seven fractions over 2.3 weeks. RESULTS: Of the 19 patients, 15 achieved local control 3-51 months after reirradiation. No patient suffered from acute reaction, but one patient with a history of extensive radiotherapy developed progressive radionecrosis 9 months after reirradiation. CONCLUSIONS: Fractionated stereotactic radiotherapy of intracranial recurrences appears to be effective in achieving in local control with negligible morbidity. We believe it merits further investigation in a prospective study.

High dose rate brachytherapy for carcinoma of the uterine cervix: comparison of two different fractionation regimens.

PURPOSE: There is no consensus as to the best dose-fractionation regimen in high dose rate (HDR) brachytherapy for cervix cancer. Since 1983, two fractionation regimens have been used in different time periods at National Cancer Center Hospital, and their treatment results have been compared in terms of 5-year survival, local control, and complication rate to find the better therapeutic regimen. METHODS AND MATERIALS: From November 1983 to October 1990, 130 patients with uterine cervix carcinoma were treated with HDR intracavitary brachytherapy using a remote afterloading system. There were 21 Stage Ib patients, 5 Stage IIa, 29 Stage IIb, 2 Stage IIIa, 68 Stage IIIb, and 5 Stage IVa. The median age was 64 years. The median follow-up time was 50 months. Radiotherapy consisted of external beam irradiation to the pelvis (mean dose of 50 Gy), combined with HDR brachytherapy (mean dose of 20 Gy to point A) given 5 Gy per session twice weekly (group A: 54 patients) or 6 Gy once weekly (group B: 76 patients). RESULTS: The overall 5-year survival was 52% in group A and 72% in group B. Local recurrence rate was 11%, and distant failure rate was 21%, with no difference between the two groups. The complication rate was significantly lower in group B (37%) than in group A (55%). Multivariate analysis has shown that factors affecting survival were stage, brachytherapy dose, and local control status. No factor was predictive of local control, but the external beam radiation dose significantly influenced the risk of complications. CONCLUSION: The once-weekly HDR intracavitary applications combined with properly adjusted external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer.

Fractionated stereotactic radiotherapy of small intracranial malignancies.

PURPOSE: To retrospectively evaluate the effectiveness of fractionated stereotactic radiotherapy (FSRT) in patients with small intracranial malignancies. METHODS AND MATERIALS: From July 1991 to March 1997, 80 patients with a total of 121 brain or skull-base tumors were treated with FSRT alone, and were followed for periods ranging from 3 to 62 months (median 9.8). The majority of patients received 42 Gy in 7 fractions over 2.3 weeks, but in July 1993, protocols using smaller fraction doses were introduced for patients whose radiation-field diameters were larger than 3 cm or whose tumors were close to critical normal tissues. RESULTS: For 64 patients with metastatic brain tumors the overall median survival was 8.3 months and 1-year actuarial survival rate was 33%. Significant prognostic factors were: the presence of extracranial tumors, pre-treatment performance status, and the lung as a primary site. Patients without extracranial tumors prior to FSRT had a median survival of 21.2 months. For seven patients with high-grade glioma, 1-year actuarial local control rate was 75%, with a median survival of 10.3 months. For patients with skull-base tumors the local control was achieved in 6 of 6 patients (100%), with a median survival of 30.7 months. No one suffered from acute complications, but three patients, two of whom had undergone FSRT as the third course of radiotherapy, developed late radiation injuries. CONCLUSION: Overall high local control and low morbidity rates suggest that FSRT is an effective and safe modality, even for those with a history of prior irradiation. However, patients with risk factors should be treated with smaller fraction doses.

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.

Linac-based small-field radiotherapy for brain tumors.

Small-field radiotherapy based on a 6-MeV linac and a conventional head mold is investigated as an alternative to radiosurgery with stereotactic frames. The system requires no additional device and allows fractionated treatment. The dose distributions obtained are comparable to those reported with a Gamma Unit. Overall positioning errors are within 2 mm. Using this approach, seven patients with brain tumors who could not have been treated otherwise, underwent fractionated radiotherapy with total accumulated doses ranging from 70 to 108 Gy. The treatment was tolerated well with no acute toxicity or adverse effect encountered during the follow-up period of 8-14 months. All of the patients remained free from disease progression in the treated volumes. Although the follow-up is brief, the preliminary results suggest that this is a simple and inexpensive but effective system for the treatment of small intracranial malignancies.

Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules.

Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy.

External radiotherapy for decompression of cholangiocellular carcinoma with obstructive jaundice: report of a case.

Percutaneous transhepatic catheter drainage (PTCD) is generally performed for the treatment of obstructive jaundice. However, in some cases it is difficult to perform insertion because of lack of dilatation of the intrahepatic bile duct. We report a patient who had been suffering from jaundice as a result of recurrent cholangiocarcinoma near the hilum and whose symptoms were relieved by external radiotherapy. We consider radiotherapy for cholangiocarcinoma effective palliative treatment for decompression of obstructive jaundice.

Brain involvement in Hodgkin's disease: case reports and review of the literature.

Hodgkin's disease involving in the central nervous system is extremely rare. It usually spreads contiguously, as visceral involvement is generally thought to occur secondary to involved adjacent lymph nodes. We report three such cases found in our institution in the last two decades. Based upon our limited experience together with reported data, whole brain irradiation combined with systemic chemotherapy remains the treatment of choice for these lesions.

[Improvement in function-preservation in radiotherapy for pediatric malignancies].

In radiotherapeutic management for pediatric tumors, we have to pay more attention to confinement of higher dose to the target volume than for adult tumors, in order that the risk of untoward normal tissue complications dose not increase, such as growth retardation. Two current approaches performing in our department to match this purpose are presented, namely, perioperative brachytherapy and fractionated stereotactic radiotherapy (F-SRT). In perioperative brachytherapy for bone and soft tissue sarcoma, plastic guide tubes for introducing radioactive sources are placed in the residual tumor bed or at the margins during the surgery, and patients are treated by high-dose-rate brachytherapy after surgery. Patients are not restricted in radioprotective area, and the overall treatment period is short enough. F-SRT is used either as the boost of conventional brain radiotherapy in primary brain neoplasms, or as hypofractionated F-SRT for control of metastatic brain tumors, with nearly perfect local control and maintenance of good quality of life. F-SRT is planned in 3-dimensional fashion from computed tomography images. Easily detachable, relocatable cast made for F-SRT is useful in pediatric patients.

Orbital lymphoproliferative disorders (OLPDs): value of MR imaging for differentiating orbital lymphoma from benign OPLDs.

BACKGROUND AND PURPOSE: Accurate discrimination of orbital lymphoma from benign orbital lymphoproliferative disorders is crucial for treatment planning. We evaluated MR imaging including DWI and contrast-enhanced MR imaging for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders. MATERIALS AND METHODS: Forty-seven histopathologically proved orbital lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital lymphoproliferative disorders) were evaluated. Two board-certified radiologists reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion-weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and contrast-enhancement ratio of all lesions were measured and optimal cutoff thresholds and areas under curves for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders were determined using receiver operative characteristic analysis; corresponding sensitivities and specificities were calculated. RESULTS: Multivariate logistic regression analysis showed that ill-defined tumor margin (P = .003) had a significant association with orbital lymphoma whereas the "flow void sign" (P = .005) and radiologic evidence of sinusitis (P = .0002) were associated with benign orbital lymphoproliferative disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were significantly lower than those of benign orbital lymphoproliferative disorders (P < .01). An ADC of less than 0.612 × 10(-3) mm(2)/s and a contrast-enhancement ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770, sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for predicting orbital lymphoma, respectively. CONCLUSIONS: Some characteristic MR imaging features and quantitative DWI and contrast-enhanced MR imaging are useful in further improving the accuracy of MR imaging for differentiation of orbital lymphoma from benign orbital lymphoproliferative disorders.

A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer.

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.

Prognostic factors in patients with locally advanced pancreatic carcinoma receiving chemoradiotherapy.

BACKGROUND: The combination of radiation therapy and chemotherapy (chemoradiotherapy [CRT]) has been accepted as standard therapy for patients with locally advanced pancreatic carcinoma (PC). This study investigated prognostic factors in patients with locally advanced PC receiving CRT. METHODS: Fifty-five consecutive patients with locally advanced PC, who received concurrent radiotherapy (50.4 grays) and chemotherapy using 5-fluorouracil or cisplatin, were analyzed retrospectively to investigate prognostic factors. RESULTS: Median survival time and overall survival rates at 1 and 2 years were 301 days, 35.1% and 2.4%, respectively. By multivariate analysis using the Cox proportional hazards model, performance status of 0-1 (P < 0.01), absence of regional lymph node swelling (P < 0.01), and serum CA 19-9 level of less than 1000 (P = 0.02) were independent favorable prognostic factors. A prognostic index based on the coefficients of those prognostic factors was used to classify patients into three groups with good, intermediate, and poor prognoses. The median survival times for these three groups were 410, 239, and 143 days, respectively (P < 0.01). CONCLUSIONS: The results may be helpful in predicting life expectancy, determining treatment strategies, and designing future clinical trials.

Long-term observations of a patient with choroidal melanoma following fractionated stereotactic radiotherapy: a case report.

A 60-year-old man with choroidal melanoma was treated with fractionated stereotactic radiotherapy and followed for 6 years. During this period, the tumor has not changed in size, and the patient has experienced only a slight decrease in visual acuity. In this case, stereotactic radiotherapy appears to have been safe and effective and may also be a cost-effective alternative to particle or plaque therapy.