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Purpose: To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients., Materials and Methods: 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/β 10 Gy and 3 Gy., Results: Median V85 Gy , V75 Gy and V60 Gy EQD2 10 were 72 cm 3 , 100 cm 3 and 233 cm 3 , respectively. Median V85 Gy EQD2 10 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm 3 ), intermediate (25-35 cm 3 ) and large (>35 cm 3 ) CTV HR volumes, the V85 Gy was 57 cm 3 , 70 cm 3 and 89 cm 3 , respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A., Conclusions: MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTV HR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: Structure-based deformable image registration (DIR) can be used to calculate accumulated brachytherapy (BT) and external-beam radiation therapy (EBRT) dose-volume histogram (DVH) parameters in cervical cancer. Since direct parameter addition does not take dose non-uniformity into account, the added value of DIR over addition methods was investigated for bladder and rectum., Materials and Methods: For twelve patients (EBRT: 46Gy, EBRT+BT: D 90 85-90Gy EQD2 in equivalent dose in 2Gy fractions) the EBRT planning CT and BT planning MRI were registered using DIR. Affected lymph nodes, located far from the BT boost region, received an EBRT boost (9.2Gy) not contributing to the BT boost dose. Cumulative bladder/rectum D 2cm3 /D 1cm3 were calculated and compared to direct addition methods, assuming uniform EBRT doses (UD), or overlapping high dose volumes (OHD)., Results: Between the three methods, the maximum differences in the cumulative DVH parameters were 3.2Gy EQD2 (bladder) and 3.3Gy EQD2 (rectum). The difference between DIR and UD was <1.8Gy EQD2 for both organs., Conclusions: The UD method provides a better estimate of D 2cm3 /D 1cm3 than the OHD method. There is no added value of DIR since differences with direct addition methods are clinically insignificant. EBRT dose distributions can be considered uniform in bladder and rectum for the evaluated dose parameters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: To determine the uncertainties in planned dose associated with catheter and organ movement during 48 hours of stepping source prostate brachytherapy., Material and Methods: Pulsed-dose rate (PDR) prostate brachytherapy as a boost is given in 24 pulses every 2 hours, making the total treatment last 48 hours. The entire treatment is based on one plan, created on the planning CT (CT1). Two follow-up CTs (CT2 and CT3) were acquired; halfway through the treatment and at the end of treatment. On these repeat scans the catheters were reconstructed and PTV and OARs were delineated. The original treatment plan was calculated on the repeat CTs. Target coverage V(100%), D(90), dose to 2cm(3) (D2cm(3)) of the rectum and bladder and dose to 0.1cm(3) of the urethra were recorded from the recalculated DVHs., Results: On the two repeat CTs the V100% decreased -1.5% and -2.3% as compared to the planning CT. For the rectum D2cm(3), the average increase was 14.8% (CT1-CT2) and 17.3% (CT1-CT3). Increase in bladder D2cm(3) was on average 23.1% (CT1-CT2) and 24.8% (CT1-CT3). For the urethra D0.1cm(3) an average decrease of -2% (CT1-CT2) and -3.2% (CT2-CT3) was observed., Conclusions: Changes in target coverage during treatment were small and considered clinically irrelevant. However, an overall increase in dose to the OARs was found as compared to the planned dose, which should be taken into account during treatment planning., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Catheters were developed that can be fixed in the prostate gland by self-expanding parts for use in PDR brachytherapy. Daily CT-scans were made to investigate the magnitude of catheter displacement. The mean absolute displacement during the 3 day treatment was 1.2 mm. The resulting minor alterations in dose-volume parameters were of no clinical importance.

Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time., Methods and Materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria., Results: The feasibility of the treatment was good. Severe acute toxicity >/=G3 was observed in seven patients (14%). Severe late toxicity >/=G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%., Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity.

Background and Purpose: Radiobiological studies suggest equivalent biological effects between continuous low dose rate brachytherapy (CLDR) and pulsed brachytherapy (PB) when pulses are applied without interruption every hour. However, radiation protection and institute-specific demands requested the design of a practical PB protocol substituting the CLDR boost in breast cancer patients. An office hours scheme was designed, considering the CLDR dose rate, the overall treatment time, pulse frequency and tissue repair characteristics. Radiobiological details are presented as well as the logistics and technical feasibility of the scheme after treatment of the first 100 patients., Materials and Methods: Biologically effective doses (BEDs) were calculated according to the linear quadratic model for incomplete repair. Radiobiological parameters included an alpha/beta value of 3 Gy for normal tissue late effects and 10 Gy for early normal tissue or tumour effects. Tissue repair half-time ranged from 0.1 to 6 h. The reference CLDR dose rate of 0.80 Gy/h was obtained retrospectively from analysis of patients' data. The treatment procedure was evaluated with regard to variations in implant characteristics after treatment of 100 patients., Results: A PB protocol was designed consisting of two treatment blocks separated by a night break. Dose delivery in PB was 20 Gy in two 10 Gy blocks and, for application of the 15 Gy boost, one 10 Gy block plus one 5 Gy block. The dose per pulse was 1.67 Gy, applied with a period time of approximately 1.5 h. An inter-patient variation of 30% (1 SD) was observed in the instantaneous source strength. Taking also the spread in implant size into account, the net variation in pulse duration amounted to 38%., Conclusion: An office hours PB boost regimen was designed for substitution of the CLDR boost in breast-conserving therapy on the basis of the BED. First treatment experience shows the office hour regimen to be convenient to the patients and no technical perturbations were encountered.

Background and Purpose: To analyze the treatment results of transperineal (125)Iodine seeds in localized prostate cancer., Patients and Methods: Between 1985 and 1996, 102 patients with T1-T2 N0 prostate cancer were treated with transperineal (125)Iodine seed implants at the Academic Medical Centre in Amsterdam. Tumours were classified as T1c in four patients, T2a in 73 patients and T2b in 25 patients. The mean pre-treatment PSA was 17 ng/ml. The (125)Iodine seeds were implanted transperineally under transrectal ultrasound guidance. The mean prostate volume was 31 ml (range 15-48 ml). An average of 49 seeds (range 29-74) was implanted. The dose to the periphery of the prostate was 160 Gy. Until 1988, 27 patients had additional external pelvic irradiation to a dose of 40 Gy in 20 daily fractions of 2 Gy., Results: The 5- and 7-year actuarial survival rates were 77 and 63%, respectively (median 102 months). Ten patients (9.5%) died from prostate cancer. The 5- and 7-year clinical progression rates were 12 and 17%, respectively. Biochemical failure rates at 5 and 7 years were 39 and 44%, respectively. Age, alkaline phosphatase, creatinine, differentiation grade, additional treatment, staging procedure, number of seeds, prostate volume, treatment period and PSA were analyzed as prognostic factors. Only pre-treatment PSA was a prognosticator of clinical and biochemical outcome but not of survival. Biochemical control at 6 years varied from 30% for pre-treatment PSA values higher than 20 ng/ml to 95% for values < or =8 ng/ml. Forty-one out of 49 patients who were sexually active before brachytherapy maintained sexual function during the follow-up. Complete urinary incontinence occurred in one patient. No rectal complications were seen in patients receiving brachytherapy alone., Conclusions: Transperineal (125)Iodine seeds brachytherapy in localized prostate cancer achieves a good clinical control and overall survival with acceptable late toxicity. Biochemical failure was strongly correlated to the pre-treatment PSA value.