Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial.

PURPOSE: After publication of the radiation field design in the American College of Surgeons Oncology Group Z0011 trial, a radiation therapy quality assurance review was integrated into the Intergroup-Sentinel-Mamma (INSEMA) trial. We aimed to investigate the role of patient characteristics, extent of axillary surgery, and radiation techniques for dose distribution in ipsilateral axillary levels. METHODS AND MATERIALS: INSEMA (NCT02466737) has randomized 5542 patients who underwent breast-conserving surgery. Of these, 276 patients from 108 radiation therapy facilities were included in the central review, using the planning records of the first 3 patients treated at each site. RESULTS: Of the 276 patients, 41 had major deviations (ie, no axillary contouring or submission of insufficient records) leading to exclusion. A total of 235 (85.1%) radiation therapy planning records were delineated according to the INSEMA protocol, including 9 (3.8%) cases with minor deviations. At least 25% of INSEMA patients were unintentionally treated with ≥95% of the prescribed breast radiation dose in axillary level I. Approximately 50% of patients were irradiated with a median radiation dose of more than 85% of prescription dose in level I. Irradiated volumes and applied doses were significantly lower in levels II and III compared with level I. However, 25% of patients still received a median radiation dose of ≥75% of prescription dose to level II. Subgroup analysis revealed a significant association between incidental radiation dose in the axilla and obesity. Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution. CONCLUSIONS: Assuming ≥80% of prescribed breast dose as the optimal dose for curative radiation of low-volume disease in axillary lymph nodes, at least 50% of reviewed INSEMA patients received an adequate dose in level I, even with contemporary 3-dimensional techniques. Dose coverage was much less in axillary levels II and III, and far below therapeutically relevant doses.

Radiotherapy for orbital lymphoma : outcome and late effects.

PURPOSE: To analyze the effectiveness of radiotherapy in the management of orbital non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: 42 patients (median age 64.5 years) were reviewed retrospectively. The median follow-up period was 58 months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive NHLs). 16 patients had advanced NHLs in stages II-IV with orbital involvement (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20-46 Gy) for indolent lymphoma and 44 Gy (20-48 Gy) for aggressive lymphoma. Patients with stage IE were treated with at least 30 Gy. RESULTS: The 5-year local control rate for patients with stage I was 100%, the 5-year overall survival 91%. Two distant relapses were found, but no lymphoma-related death was detected. The 5-year local control rate for patients in stages II, III, and IV was 80%. Two local failures were detected. The 5-year overall survival for the advanced stages was 47%, nine patients with stages III and IV died due to systemic progression of lymphoma. Acute, radiotherapy-related complications grade 3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six patients, treated with doses of > 36 Gy, developed grade 3 complications (four cataract, two dryness). CONCLUSION: Radiotherapy alone yields excellent local control and overall survival rates in orbital lymphoma stage IE. Local irradiation is also well tolerated and effective in advanced NHL stages with orbital infiltration. Doses of > 36 Gy resulted in an increase of late complications.

Radiation therapy of mesothelioma: the Heidelberg experience and future aspects.

Pleural mesothelioma is a rare but fatal tumour. Numerous attempts to find effective treatment approaches have, in general, been disappointing. To date, the most promising treatment is surgery, or surgery in combination with radio and chemotherapy as a part of a multidisciplinary approach. Preliminary results from clinical trials evaluating intensity modulated radiotherapy are encouraging. Further randomised trials are proposed.

External beam radiotherapy fails to prevent restenosis after iliac or femoropopliteal percutaneous transluminal angioplasty: results of a prospective randomized double-blind study.

PURPOSE: Early restenosis is one of the major complications after successful percutaneous transluminal angioplasty (PTA), in main, as well as peripheral, arteries. The effectiveness of hypofractionated external beam radiotherapy (EBRT) as a prophylaxis for restenosis was examined in a prospective, randomized, double-blind, clinical trial. METHODS AND MATERIALS: Forty-eight patients underwent sham RT and 47 were treated with daily RT in 3-Gy fractions, to a total dose of 21 Gy. The follow-up lasted for 12 months, and the examinations included pressure measurements and calculations of the ankle-brachial index or duplex sonography ("peak velocity ratio"). If restenosis was suspected, additional angiography was performed. RESULTS: No statistically significant difference was found between the treatment groups: sham RT 16 failures (33.3%) and EBRT group 21 failures (45.7%; p = 0.292). EBRT also showed no substantial effects on subgroups classified by the specific length of the lesion or in diabetic patients. CONCLUSION: External beam radiotherapy does not prevent restenosis. A reduction in the failure rate >8% using fractionated EBRT with doses aimed at keloid prevention can be ruled out with a probability of 97.5%. Endovascular brachytherapy remains the preferred therapeutic method for achieving restenosis prophylaxis through RT.

[Male gonadal dose in adjuvant 3-d-pelvic irradiation after anterior resection of rectal cancer. Influence to fertility]. / Radiogene Hodenbelastung durch Streustrahlung bei adjuvanter 3-D-Beckenbestrahlung nach anteriorer Resektion beim RektumkarzinomEinfluss auf die Fertilität.

BACKGROUND: Rectal cancer is a common malignant disease and occurs not infrequently in younger men. We verified the dose to the testes from scattered radiation in adjuvant pelvic irradiation following anterior resection of rectal cancer. PATIENTS AND METHOD: We measured the scattered gonadal dose of 18 patients in vivo with thermoluminescence detectors, which were fixed on four defined points on the scrotum during radiation on three consecutive days. All patients were treated three-dimensionally planned using a three-field box lying in prone position in a bellyboard. A total dose of 50.4 Gy was given in 28 fractions of 1.8 Gy. From 45 up to 50.4 Gy the radiation fields were modified to lateral-opposing fields which were shortened from the top to protect the small bowel. RESULTS: The mean gonadal dose per fraction of all patients was 0.057 Gy (median 0.05 Gy) with a range between 0.035 and 0.114 Gy. The standard deviation was 0.02 Gy. The calculated cumulative mean gonadal dose after 28 fractions was 1.60 Gy (0.98-3.19 Gy). CONCLUSIONS: Germinal epithelium is very sensitive to low-dose irradiation, according to a negative fractionation effect. It is known that gonadal total doses of 1 Gy with single doses of 0.03-0.05 Gy can result in a temporary azoospermia with following recovery in most cases. If gonadal total doses exceed 1.5 Gy a substantial increase in irreversible azoospermia must be expected. With respect to the data reported in the literature our measured mean gonadal total dose of 1.60 Gy will lead with high probability to an irreversible infertility. Because of the small number of patients in our study, the data must be interpreted with caution, however, it is very important in patient's informed consent to draw attention to the high risk of infertility. The possibility of sperm cryoconservation should be discussed with the patient.

Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients.

PURPOSE: Stereotactic radiosurgery is an alternative option to neurosurgical excision in the management of patients with brain metastases. We retrospectively analyzed patients with brain metastases of malignant melanoma who were treated at our institution for outcome and prognostic factors. PATIENTS AND METHODS: 64 patients with 122 cerebral metastases were treated with stereotactic radiosurgery between 1986 and 2000. Twelve patients (19%) showed neurologic symptoms at the time of treatment, and 46 patients (72%) had extracerebral tumor manifestation at that time. The median dose to the 80% isodose line, prescribed to encompass the tumor margin, was 20 Gy (range, 15-22 Gy). RESULTS: Neurologic symptoms improved in five of twelve symptomatic patients. 41 patients remained asymptomatic or unchanged in their neurologic symptoms. Only five patients (8%) temporarily worsened neurologically after therapy despite no signs of tumor progression. With a mean follow-up time of 9.4 months, actuarial local control was 81% after 1 year. There was a statistically significant dose and size dependency of local tumor control. Median actuarial survival after treatment was 10.6 months. Patients without extracerebral tumor manifestation showed a superior survival (p = 0.04). CONCLUSIONS: Despite high local tumor control rates, the prognosis of patients with cerebral metastases of malignant melanoma remains poor. Stereotactic radiosurgery has the potential of stabilizing or improving neurologic symptoms in these patients in a palliative setting.

[Concurrent chemotherapy and radiation therapy for unresectable locally advanced carcinoma of the esophagus. Phase II study and clinical review on literature]. / Primäre Radiochemotherapie inoperabler fortgeschrittener Osophaguskarzinome. Ergebnisse einer Phase-II-Studie und Literaturübersicht.

BACKGROUND: Neither surgical advances nor those in therapeutic radiology have been able to significantly reduce the mortality related to esophageal carcinomas. The results of combining: first surgery, then radiation therapy, which have been unsatisfactory for decades, encourage therapeutic concepts involving a variety of modalities. PATIENTS AND METHODS: For 50 patients with unresectable locally advanced esophageal carcinomas, a palliative concurrent chemotherapy and radiation therapy was carried out according to the "intent to treat" principle. The aim was a minimal dose of 40 Gy. The concurrent chemotherapy was carried out using cisplatin/5-FU during the 1st and 4th weeks of radiation therapy. In the case of partial or complete remission, the chemotherapy was to be continued as maintenance therapy with a maximum of four cycles. In the case of no change or minor response, instead of maintenance chemotherapy, the dose of local radiation was to be increased by means of brachytherapy. RESULTS: The median survival rate for the entire population under study was 8.7 months. The survival rates of 1, 2, 3, 4, and 5 years were, respectively, 38%, 20.5%, 13.7%, 6.8%, and 6.8%. The remission rates were as follows: NC: 14 patients (28%), PR: 32 patients (64%), CR: 4 patients (8%). 17 patients (34%) tolerated the full concurrent chemotherapy; only twelve patients (24%) tolerated supportive chemotherapy. The following factors exhibited a significant correlation to survival: the intensity of the chemotherapy, the Karnofsky index, the age of the patients, and the improvement of oral food intake. CONCLUSIONS: The concurrent chemotherapy was toxic and the benefit to the patients questionable. At best, meta-analyses of randomized studies along the lines of "evidence-based medicine" demonstrate for concurrent chemotherapy and radiation therapy an improvement of 2-year survival rates, but with these also involving a high level of toxicity. Due to the heterogeneous data available, the value of the primary, sequential treatment combining chemotherapy and radiation therapy is uncertain.

Open low-field magnetic resonance imaging in radiation therapy treatment planning.

PURPOSE: To evaluate the possibilities of an open low-field magnetic resonance imaging (MRI) scanner in external beam radiotherapy treatment (RT) planning. METHODS AND MATERIALS: A custom-made flat tabletop was constructed for the open MR, which was compatible with standard therapy positioning devices. To assess and correct image distortion in low-field MRI, a custom-made phantom was constructed and a software algorithm was developed. A total of 243 patients (43 patients with non-small-cell lung cancer, 155 patients with prostate cancer, and 45 patients with brain tumors) received low-field MR imaging in addition to computed tomographic (CT) planning imaging between January 1998 and September 2001 before the start of the irradiation. RESULTS: Open low-field MRI provided adequate images for RT planning in nearly 95% of the examined patients. The mean and the maximal distortions 15 cm around the isocenter were reduced from 2.5 mm to 0.9 mm and from 6.1 mm to 2.1 mm respectively. The MRI-assisted planning led to better discrimination of tumor extent in two-thirds of the patients and to an optimization in lung cancer RT planning in one-third of the patients. In prostate cancer planning, low-field MRI resulted in significant reduction (40%) of organ volume and clinical target volume (CTV) compared with CT and to a reduction of the mean percentage of rectal dose of 15%. In brain tumors, low-field MR image quality was superior compared with CT in 39/45 patients for planning purposes. CONCLUSIONS: The data presented here show that low-field MRI is feasible in RT treatment planning when image correction regarding system-induced distortions is performed and by selecting MR imaging protocol parameters with the emphasis on adequate images for RT planning.

[Lung dose depending on exact patient positioning during total body irradiation (TBI). Isoeffectiveness considerations to assess the risk of interstitial pneumonia after TBI]. / Lungendosis in Abhängigkeit von der Lagerungsgenauigkeit bei Ganzkörperbestrahlungen (TBI). Isoeffektivitätsüberlegungen zur Einschätzung des Risikos einer interstitiellen Pneumonitis nach Ganzkörperbestrahlung.

PURPOSE: In this case report, we studied the effect of patient's movements on total lung dose during total body irradiation (TBI). The dose-effect relationship regarding the development of interstitial pneumonitis and the problem of defining a threshold value are discussed. Based on considerations about the isoeffects we calculated the pneumonitis risk in dependence of increasing lung dose. PATIENTS AND METHOD: We calculated dose-volume histograms of the lung for defined lateral deviations (0-3 cm) from the isocenter. Total dose was 12 Gy, given in six fractions over 3 days. Lung shields were used after a total dose of 9 Gy. Lung shields were transferred into the Helax-TMS planning system to quantify the influence of lateral deviation to lung dose. RESULTS: The child's lateral deviation amounted up to 3 cm. Median dose of the whole lung amounted up to 11.64 Gy depending on lateral deviation. DISCUSSION: In TBI, the lung limits the total dose. To estimate the risk of radiation pneumonitis, we calculated the isoeffective lung dose of our TBI regime for a fractionation scheme of 2 Gy daily using a formalism of van Dyk. The increase of median lung dose from 9.76 to 11.64 Gy would isoeffectively correspond to the increase from 19 Gy (no deviation) to 20.9 Gy (3 cm lateral deviation) with conventional fractionation. According to Burman, a pneumonitis risk of approximately 20% could be expected. CONCLUSION: With an estimated pneumonitis risk of approximately 20%, in indication for irradiation in general anesthesia seems to be reasonable. This is practicable in cooperation with radiation oncologists, anesthesists and pediatricians and should be included into therapeutic concepts.

The role of radiation therapy in the management of desmoid tumors.

PURPOSE: To investigate the role of radiation therapy (RT) in the management of desmoid tumors. PATIENTS AND METHODS: Retrospective analysis was performed on 28 patients with desmoid tumors treated with radiation therapy between March 1989 and March 1999. Tumor site was intraabdominal in three, abdominal wall in three and extraabdominal in 22 patients. Median tumor dose was 48 Gy (range 36-60 Gy). Radiation therapy was delivered postoperatively in 26 of 28 patients, two patients received radiation therapy for unresectable recurrent tumors. RESULTS: Median follow-up was 46 months (range 13-108 months). Actuarial 5-year control rate was 73%. We observed six recurrences, located within the radiation field in one patient, out of field in two and at the field margin in three patients. All patients with intraabdominal tumors have been controlled without severe side effects. CONCLUSIONS: Radiation therapy is an effective treatment after incomplete resection of desmoid tumors. We did not observe a benefit for tumor doses exceeding 50 Gy. In some patients with circumscribed intraabdominal desmoid tumors, radiation therapy might be a treatment option with low toxicity, if 3-D treatment planning is utilized.

Inverse planning and intensity-modulated radiotherapy in patients with prostate cancer.

Inverse planning and IMRT are methods with the potential to improve substantially clinical results in radiotherapy of prostate cancer. Available early clinical data demonstrate the feasibility and safety of high-dose IMRT for patients with localized prostate cancer and provide a proof-of-principle that this method improves dose conformality relative to tumor coverage and exposure to normal tissues.