Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients.

PURPOSE: Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT. METHODS AND MATERIALS: Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction. RESULTS: A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted. CONCLUSIONS: ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.

The influence of geometrical changes on the dose distribution after I-125 seed implantation of the prostate.

PURPOSE: After prostate implantation, dose calculation is usually based on a single imaging session, assuming no geometrical changes occur during the months of dose accumulation. In this study, the effect of changes in anatomy and implant geometry on the dose distribution was investigated. MATERIALS AND METHODS: One day, 1 month and 312 months after seed implantation, a combined TRUS-CT scan was made of 13 patients. Based on these scans changes in dose rate distribution were determined in prostate, urethra and bladder and a 'geometry corrected' dose distribution was estimated. RESULTS: When based on the day-1 scan, parameters representing high dose volumes in prostate and urethra were largely underestimated: V150 of the prostate 18+/-10% and V120 of the urethra 47+/-32%. The dose to a 2cm(3) hotspot in the bladder wall (D2cc), however, was overestimated by 31+/-35%. Parameters based on scans 1 month post-implant or later were all within +/-5% of geometry corrected values. CONCLUSION: Values meant to indicate the adequacy of dose coverage of the prostate, V100 and D90, were not influenced by geometrical changes and were independent of the post-implant scan date. Other parameters representing high dose volumes changed strongly within the first month after implantation.

Re-irradiation of the human spinal cord.

PURPOSE: Experimental animal data give evidence of long-term recovery of the spinal cord after irradiation. By extrapolation of these data, re-irradiation regimens were designed for eight patients who required palliative radiotherapy. As a consequence of re-irradiation, their spinal cords were exposed to cumulative doses exceeding the tolerance dose. Radiobiological and clinical data are presented. PATIENTS AND METHOD: Eight patients were re-irradiated on the cervical (n = 1), thoracic (n = 5) and lumbar (n = 2) spinal cord. The time interval between the initial and re-treatment ranged from 4 months to 12.7 years (median: 2.5 years). (Re-)treatment schemes were designed and analyzed on basis of the biologically effective dose (BED) according to the linear-quadratic model. The repair capacity (alpha/beta ratio) for the cervico-thoracic and lumbar spinal cord was assumed to be 2 Gy and 4 Gy, with a BEDtolerance of 100 Gy and 84 Gy, respectively. RESULTS: The cumulative irradiation dose applied to the spinal cord varied between 125 and 172% of the BEDtolerance. During follow-up, ranging from 33 days to > 4.5 years (median: 370 days) none of the patients developed neurological complications. Seven patients died from tumor progression, and one patient is still alive. CONCLUSION: Long-term recovery of the spinal cord from radiation injury, which has been demonstrated in rodents and primates, may also occur in humans.

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate.

BACKGROUND AND PURPOSE: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). METHODS AND MATERIALS: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. RESULTS: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED(NT/TUM) ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor and normal tissue repair half-times and equal overall treatment time. For the same fraction size, an even larger normal tissue sparing can be obtained by prolongation of the HDR overall treatment time. CONCLUSION: Radiobiologic model calculations presented here aim to demonstrate that hypofractionation in HDR might have its opportunities for widening the therapeutic window, but definitely has its limits. For each specific combination of the parameters, a theoretical optimal HDR fraction size with regard to relative or absolute normal tissue sparing can be estimated, but because of uncertainty in the biologic parameters, these hypofractionation schemes cannot be generalized for all HDR brachytherapy indications.