Appropriate radiation dose for symptomatic relief and local control in patients with adult T cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm that occurs only in patients with human T-cell leukemia virus type 1. No large study or randomized trial investigating radiotherapy (RT) for ATL has been performed. We retrospectively reviewed 55 courses of RT for 41 consecutive patients with ATL who underwent RT between 2000 and 2016 at our institutions. The results showed that RT for local ATL lesions can achieve symptomatic improvement in 92% of cases. Local remission, either complete remission (CR) or partial response (PR), was achieved in 100% of the patients (CR: 89%, PR: 11%) with ≥40 Gy irradiation. CR or PR was achieved in 71% (CR: 29%, PR: 43%) with 30-39 Gy and in 73% (CR: 6.7%, PR: 67%) with ≤29 Gy irradiation. The mean total radiation dose in the CR and PR groups differed significantly (38 vs 25 Gy, P = 0.0002). The maximum acute toxicity was Grade 0-2 in all patients, except for one patient experienced Grade 3 radiation dermatitis. In-field relapses occurred in 36% of patients, and the frequency of in-field relapses was 11%, 30% and 71% among those who achieved CR, PR and SD, respectively. All 9 patients who received total skin irradiation experienced cutaneous relapses, with a median of 63 days (range, 7-210 days). Almost all (39 of 41) patients with ATL experienced out-of-field progression after RT. In conclusion, RT was confirmed to be effective and safe for palliative treatment of local ATL lesions.

Computed tomography-based image-guided brachytherapy for cervical cancer: correlations between dose-volume parameters and clinical outcomes.

This study evaluated the oncologic outcomes and complications of cervical cancer patients in terms of CT-based image-guided brachytherapy (IGBT) parameters. Of 68 cervical cancer patients treated with definitive radiotherapy/concurrent chemoradiotherapy, most received whole-pelvis external beam RT (EBRT) of 40 Gy in 20 fractions, pelvic EBRT with central shield of 10 Gy in 5 fractions, and CT-based IGBT of 18 Gy in 3 fractions prescribed to point A. Cumulative EBRT and IGBT doses were calculated as the total equivalent dose in 2 Gy fractions (EQD2). The median follow-up was 31 (3-52) months. The 2-year overall survival, local control, pelvic control, and disease-free survival rates of the 68 patients were 92%, 83%, 82% and 73%, respectively. The HR-CTV D90, length from the tandem axis to left/right margin of the HR-CTV (T-LR), and HR-CTV volume were significant IGBT parameters for predicting local/pelvic control. Patients who received an HR-CTV D90 of >60 Gy, compared with ≤60 Gy, had significantly better local/pelvic control. Furthermore, 70 Gy was a marginally significant HR-CTV D90 cut-off affecting local control. T-LR was an independent IGBT parameter predicting local/pelvic control on multivariate analysis. Three patients developed Grade 3 or higher treatment-related complications. The D2cm3 of organs at risk were not significant predictors of complications. Future challenges for further improving outcomes include additional interstitial needles for irregularly shaped HR-CTVs, and moderate dose escalation, especially for patients with poor tumor responses.

Educational outcomes of a medical physicist program over the past 10 years in Japan.

The promotion plan for the Platform of Human Resource Development for Cancer (Ganpro) was initiated by the Ministry of Education, Culture, Sports, Science and Technology of Japan in 2007, establishing a curriculum for medical physicists. In this study, we surveyed the educational outcomes of the medical physicist program over the past 10 years since the initiation of Ganpro. The Japan Society of Medical Physics mailing list was used to announce this survey. The questionnaire was created by members of the Japanese Board for Medical Physicist Qualification, and was intended for the collection of information regarding the characteristics and career paths of medical physics students. Students who participated in the medical physics program from 2007 to 2016 were enrolled. Thirty-one universities (17 accredited and 14 non-accredited) were represented in the survey. In total, 491, 105 and 6 students were enrolled in the Master's, Doctorate and Residency programs, respectively. Most students held a Bachelor's degree in radiological technology (Master's program, 87%; Doctorate program, 72%). A large number of students with a Master's degree worked as radiological technologists (67%), whereas only 9% (n = 32) worked as medical physicists. In contrast, 53% (n = 28) of the students with a Doctorate degree worked as medical physicists. In total, 602 students (from 31 universities) completed the survey. Overall, although the number of the graduates who worked as medical physicists was small, this number increased annually. It thus seems that medical institutions in Japan are recognizing the necessity of licensed medical physicists in the radiotherapy community.

[Current Status and Perspective of Chemoradiotherapy for Uterine Cervical Cancer].

Fifteen years has passed since the NCI announced the clinical importance of concurrent chemoradiotherapy (CCRT) in radiotherapy for patients with locoregionally advanced uterine cervical cancer. Numerous clinical trials have been performed to further improve the outcomes of CCRT. In addition to investigations of chemotherapeutic regimens and schedules, adaptation of novel radiotherapy methods such as image-guided brachytherapy (IGBT) and intensity-modulated radiotherapy (IMRT) is encouraged in CCRT for cervical cancer.

Occupational radiation monitoring at a large medical center in Japan.

Occupational radiation dose monitoring is a method of ensuring that radiation levels are within the regulatory limits. Our objective in this study was to evaluate the radiation doses experienced by personnel at a radiology facility between 2001 and 2010. Overall, 2418 annual dose records for workers who were categorized into four occupational groups were analyzed. The groups included: (1) radiologists, (2) radiologic technologists, (3) nurses, and (4) other workers, who belong to other hospital departments, but who participate partially in some radiologic procedures. The dose distribution was found to be skewed, with 76 % of personnel having received no measurable doses and almost 2 % having received doses of more than 2 mSv. The weighted-average annual doses ranged from 0.13 to 0.57, 0.9 to 2.12, 0.01 to 0.19, and 0.01 to 0.09 mSv for the radiologists, radiologic technologists, nurses, and the other workers, respectively. The radiologic technologists received the highest radiation exposure among the four groups. It was found that the average annual doses were decreasing over time for the radiologists, radiologic technologists, and others, whereas they were increasing for the nurses. Nurses play an important role in assisting radiologists and patients during various radiologic procedures, which might have increased their average annual dose. During the 10-year period of this study, there was no incidence of a dose exceeding the annual dose limit of 20 mSv. Furthermore, there was no detectable neutron exposure.

Postoperative radiotherapy for uterine cervical cancer: impact of lymph node and histological type on survival.

AIM: To retrospectively analyze the treatment results of postoperative radiotherapy (PORT) in patients with early-stage uterine cervical cancer. PATIENTS AND METHODS: Records of 141 patients with stage IB-IIB uterine cervical cancer treated with PORT from 1985 to 2004 were retrospectively reviewed. The majority of patients received whole-pelvic radiotherapy with antero-posterior fields, and the total radiation doses ranged from 10.8-60 Gy (median: 50.4 Gy). The median follow-up of all 141 patients was 106 months (range: 0.8-273.7 months). RESULTS: Multivariate analysis revealed that positive lymph node status (p=0.001) and histological type (p=0.015) were independent prognostic factors for overall survival. The group with three or more involved lymph nodes was significantly more likely to have extra-pelvic recurrence when compared with the groups with no (p=0.006) and up to two lymph nodes (p=0.024), respectively. CONCLUSION: PORT yielded excellent pelvic control rates for early-stage uterine cervical cancer. Lymph node status and histological type were significant prognostic factors for overall survival of patients with these tumors.

External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer.

The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1-4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10-60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6-10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3-142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.

Radical radiotherapy for superficial esophageal cancer: impact of clinical N stage on survival.

AIM: To retrospectively analyze the results of radical radiotherapy for patients with superficial esophageal cancer (SEC). PATIENTS AND METHODS: Forty-eight patients with SEC were reviewed. The median dose of external beam radiotherapy was 66 Gy (range, 30 to 70 Gy). Intraluminal brachytherapy was used in 10 patients, and 15 patients (31%) underwent chemotherapy. The median follow-up period was 28 months (range, 4 to 116 months). RESULTS: Sixteen patients had recurrence (11 patients: in-field local recurrence; 3 patients: regional lymph node recurrence; 2 patients: distant metastasis), and the 5-year local control (LC) rate was 74.2%. The 5-year overall survival and disease-free survival (DFS) rates were 44.5% and 48.6%, respectively. Patients with clinical N1 disease (5-year DFS: 0%) had significantly poorer DFS than patients with clinical N0 disease (5-year DFS: 51%, p=0.019). CONCLUSION: Radical radiotherapy yielded relatively favorable LC rates in patients with SEC, and clinical N stage was a significant prognostic factor for DFS.

Investigation of thermal and temporal responses of ionization chambers in radiation dosimetry.

The ionization chamber is a primary dosimeter that is used in radiation dosimetry. Generally, the ion chamber response requires temperature/pressure correction according to the ideal gas law. However, this correction does not consider the thermal volume effect of chambers. The temporal and thermal volume effects of various chambers (CC01, CC13, NACP parallel-plate, PTW) with different wall and electrode materials have been studied in a water phantom. Measurements were done after heating the water with a suitable heating system, and chambers were submerged for a sufficient time to allow for temperature equilibrium. Temporal results show that all chambers equilibrate quickly in water. The equilibration time was between 3 and 5 min for all chambers. Thermal results show that all chambers expanded in response to heating except for the PTW, which contracted. This might be explained by the differences in the volumes of all chambers and also by the difference in wall material composition of PTW from the other chambers. It was found that the smallest chamber, CC01, showed the greatest expansion. The magnitude of the expansion was ~1, 0.8, and 0.9% for CC01, CC13, and parallel-plate chambers, respectively, in the temperature range of 295-320 K. The magnitude of the detected contraction was <0.3% for PTW in the same temperature range. For absolute dosimetry, it is necessary to make corrections for the ion chamber response, especially for small ion chambers like the CC01. Otherwise, room and water phantom temperatures should remain within a close range.

Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: long-term results.

PURPOSE: To analyze the long-term results of a Phase II trial of radiotherapy given immediately after hyperbaric oxygenation (HBO) with multiagent chemotherapy in adults with high-grade gliomas. METHODS AND MATERIALS: Patients with histologically confirmed high-grade gliomas were administered radiotherapy in daily 2 Gy fractions for 5 consecutive days per week up to a total dose of 60 Gy. Each fraction was administered immediately after HBO, with the time interval from completion of decompression to start of irradiation being less than 15 minutes. Chemotherapy consisting of procarbazine, nimustine, and vincristine and was administered during and after radiotherapy. RESULTS: A total of 57 patients (39 patients with glioblastoma and 18 patients with Grade 3 gliomas) were enrolled from 2000 to 2006, and the median follow-up of 12 surviving patients was 62.0 months (range, 43.2-119.1 months). All 57 patients were able to complete a total radiotherapy dose of 60 Gy immediately after HBO with one course of concurrent chemotherapy. The median overall survival times in all 57 patients, 39 patients with glioblastoma and 18 patients with Grade 3 gliomas, were 20.2 months, 17.2 months, and 113.4 months, respectively. On multivariate analysis, histologic grade alone was a significant prognostic factor for overall survival (p < 0.001). During treatments, no patients had neutropenic fever or intracranial hemorrhage, and no serious nonhematologic or late toxicities were seen in any of the 57 patients. CONCLUSIONS: Radiotherapy delivered immediately after HBO with multiagent chemotherapy was safe, with virtually no late toxicities, and seemed to be effective in patients with high-grade gliomas.

Severe late complications in patients with uterine cancer treated with postoperative radiotherapy.

AIM: Severe late complications, particularly radiation enterocolitis and leg edema, remain major problems in patients with uterine cancer, who have undergone hysterectomy and postoperative external beam radiotherapy (EBRT). We carried out this retrospective analysis to identify the incidence of risk factors for such complications. PATIENTS AND METHODS: The records of 228 patients, who underwent radical hysterectomy and postoperative EBRT (uterine cervix: 149 patients; uterine corpus: 79 patients) were reviewed retrospectively. The majority of the patients (90.8%) were treated with 50 to 50.4 Gy EBRT in conventional fractionations with anteroposterior fields. Intracavitary brachytherapy (ICBT) was administered to 9 patients (3.9%), and 35 patients (15.2%) received chemotherapy. The median follow-up for all 228 patients was 81.7 months (range, 1-273 months). RESULTS: Nineteen patients (8.3%) developed severe radiation enterocolitis with a median latency of 12.6 months, and the ileum was the most frequently affected site. On multivariate analysis, smoking was an independent predictor of severe radiation enterocolitis. Nineteen patients (8.3%) developed severe leg edema with a median latency of 32.7 months. The degree of leg edema did not improve in any of the 19 patients despite intensive treatment. On multivariate analysis, addition of ICBT was an independent predictor of severe leg edema. CONCLUSION: Severe radiation enterocolitis and severe leg edema were each observed in approximately 8% of patients with uterine cancer, who underwent postoperative radiotherapy. Severe radiation enterocolitis correlated strongly with smoking, and severe leg edema correlated strongly with addition of ICBT. These factors should be considered before administering postoperative radiotherapy to uterine cancer patients.

Pulmonary nodules: a quantitative method of diagnosis by evaluating nodule perimeter difference to approximate oval using three-dimensional CT images.

The purpose of this study was to investigate whether maximum nodule perimeter to the approximate oval could discriminate benign nodules from malignancy. Measurement of maximum nodule perimeter difference to the approximate oval was performed using volume-rendering images of three directions of each pulmonary nodule. The margin was then traced manually and our custom software delineated the approximate oval automatically. The maximum nodule perimeter difference was 26.5±23.3 mm for malignant and 16.6±16.9 mm for benign nodules, showing an almost statistically significant difference (P=.07). This study suggests that the maximum nodule perimeter difference to the approximate oval of the malignant nodules has a tendency to be longer than benign nodules.

Development of gastro-lymphatic fistula during chemoradiotherapy for advanced esophageal cancer: a case report.

This is a case report of a gastro-lymphatic fistula which appeared during chemoradiotherapy for advanced esophageal cancer. A 60-year-old male was referred to the University of the Ryukyus Hospital because of a 10 kg monthly weight loss and dysphagia. Computed tomography (CT) scans indicated thickened esophageal wall at the lower thoracic esophagus and a swollen lymph node attached to the lesser curvature of the stomach. Histological analysis of the biopsy specimen revealed poorly differentiated squamous cell carcinoma and the diagnosis was of advanced esophageal cancer. A combination of chemotherapy (nedaplatin and 5-fluorouracil) and radiotherapy was initiated. After radiotherapy (20 Gy), CT scans revealed that the swollen lymph node penetrated the gastric wall resulting in a gastro-lymphatic fistula. Although gastrostomy and intestinal fistula repair were performed for gastric decompression and tube feeding, respectively, the patient's general status did not improve and he died two months after interruption of his chemoradiotherapy. The results indicate that there may be some risks of gastro-lymphatic fistula in patients treated with concurrent chemoradiotherapy for advanced esophageal cancer when there are possible signs of involvement by CT scans.

Spinal recurrence from intracranial germinoma: risk factors and treatment outcome for spinal recurrence.

PURPOSE: To analyze retrospectively the risk factors of spinal recurrence in patients with intracranial germinoma and clinical outcomes of patients who developed spinal recurrence. METHODS AND MATERIALS: Between 1980 and 2007, 165 patients with no evidence of spinal metastases at diagnosis were treated with cranial radiotherapy without spinal irradiation. The median follow-up in all 165 patients was 61.2 months (range, 1.2-260.1 months). RESULTS: After the initial treatment, 15 patients (9.1%) developed spinal recurrences. Multivariate analysis revealed that large intracranial disease (>/=4 cm) and multifocal intracranial disease were independent risk factors for spinal recurrence. Radiation field, total radiation dose, and the use of chemotherapy did not affect the occurrence of spinal recurrences. Of the 15 patients who experienced spinal recurrence, the 3-year actuarial overall survival and disease-free survival (DFS) rates from the beginning of salvage treatments were 65% and 57%, respectively. In the analysis, presence of intracranial recurrence and salvage treatment modality (radiotherapy with chemotherapy vs. radiotherapy alone) had a statistically significant impact on DFS. The 3-year DFS rate in patients with no intracranial recurrence and treated with both spinal radiotherapy and chemotherapy was 100%, whereas only 17% in patients with intracranial recurrence or treated with radiotherapy alone (p = 0.001). CONCLUSION: Large intracranial disease and multifocal intracranial disease were risk factors for spinal recurrence in patients with intracranial germinoma with no evidence of spinal metastases at diagnosis. For patients who developed spinal recurrence alone, salvage treatment combined with spinal radiotherapy and chemotherapy was effective in controlling the recurrent disease.

[Concurrent chemoradiotherapy for squamous cell carcinoma of the anal canal-report of four cases].

We have treated four Japanese patients with squamous cell carcinoma of the anal canal using concurrent chemoradiotherapy. The chemotherapy consisted of one or two cycles of mitomycin C 10 mg/m(2)/day (intravenous bolus injection) on day 1, and 5-fluorouracil 700 or 1,000 mg/m(2)/day (continuous intravenous infusion) on days 2-5 during radiotherapy. The total radiation dose was 40-54 Gy to the primary lesion. Acute grade 4 hematological toxicity was observed in one patient. These four patients have been alive and free of disease (follow-ups of 55, 14, 7 and 5 months, respectively), with excellent function of the anal sphincter after treatment. These results suggest that concurrent chemoradiotherapy is safe and effective for Japanese patients with squamous cell carcinoma of the anal canal.

Treatment and prognosis of brain metastases from gynecological cancers.

Brain metastases from gynecological cancers were retrospectively investigated in 18 patients who were treated between 1985 and 2006. Six patients received surgical resection followed by radiotherapy, and 12 patients received only radiotherapy. The median survival for all patients was 4.1 months (range 0.7-48.2 months), and the actuarial survival rates were 11% at both 12 months and 24 months. Univariate analysis showed that treatment modality, extracranial disease status, total radiation dose, number of brain metastases, and Karnofsky performance status (KPS) all had statistically significant impacts on survival. Two patients survived for more than 2 years, and both had single brain metastasis, inactive extracranial disease, 90-100% KPS, and were treated with surgical resection followed by radiotherapy. Improvements in neurological symptoms were observed in 10 of the 12 patients treated with palliative radiotherapy, with median duration of 3.1 months (range 1.5-4.5 months). The prognoses for patients with brain metastases from gynecological cancers were generally poor, although selected patients may survive longer with intensive brain tumor treatment. Palliative radiotherapy was effective in improving the quality of the remaining life for patients with unfavorable prognoses.

Treatment and prognosis of brain metastases from breast cancer.

BACKGROUND: To analyze retrospectively the results of treatments for patients with brain metastases from breast cancer. MATERIALS AND METHODS: The records of 65 breast cancer patients with brain metastases who were treated between 1985 and 2005 were reviewed. For brain metastases, 11 patients (17%) were treated with surgical resection followed by radiotherapy, and the remaining 54 patients were treated with radiotherapy alone. Systemic chemotherapy was also administered to 11 patients after brain radiotherapy. RESULTS: The overall median survival for all patients was 6.1 months (range, 0.4-82.2 months). In univariate analysis, treatment modality, Karnofsky performance status (KPS), administration of systemic chemotherapy, extracranial disease status and total radiation dose each had significant impact on overall survival, and in multivariate analysis, treatment modality, KPS and administration of systemic chemotherapy were significant prognostic factors. Eight patients survived for more than 2 years after the diagnosis of brain metastases, and all these patients were treated with surgical resection and/or systemic chemotherapy in addition to radiotherapy. For the 45 patients treated with palliative radiotherapy (without systemic chemotherapy), the improvements in neurological symptoms were observed in 35 patients (78%), with the median duration of improvement of 3.1 months (range, 1.5-4.4 months). CONCLUSIONS: The prognoses for patients with brain metastases from breast cancer were generally poor, although selected patients may survive longer with intensive brain tumor treatment, such as surgical resection and/or systemic chemotherapy in addition to brain radiotherapy. For patients with unfavorable prognoses, palliative radiotherapy was effective in improving the quality of the remaining lifetime.

Radiation enterocolitis requiring surgery in patients with gynecological malignancies.

PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of radiation enterocolitis requiring surgery in patients with gynecologic malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with pelvic radiotherapy were retrospectively reviewed. The majority of the patients (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%) developed radiation enterocolitis requiring surgery. Terminal ileum was the most frequent site (50%) and most of the lesions had stenosis or perforation. On univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM), smoking and primary site had an impact on the complications, and on multivariate analysis, abdominopelvic surgery, DM, and smoking were independent predictors of the complications requiring surgery. After the surgical intervention, the frequency of Grade 2 or more bleeding was significantly lower in patients treated with intestinal resection in addition to decompression than those treated with intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis requiring surgery usually occurred at the terminal ileum and was strongly correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the management, liberal resection of the affected bowel appears to be the preferable therapy.