Kees Koedooder

INFLUENCE OF BLADDER AND RECTAL VOLUME ON SPATIAL VARIABILITY OF A BLADDER TUMOR DURING RADICAL RADIOTHERAPY

PURPOSE To assess the spatial variability of a bladder tumor relative to the planning target volume boundaries during radical radiotherapy, and furthermore to develop strategies to reduce spatial variability. METHODS AND MATERIALS Seventeen patients with solitary T2-T4N0M0 bladder cancer were treated with a technique delivering 40 Gy/2 Gy in 20 fractions to the whole bladder with a concomitant boost to the bladder tumor of 20 Gy in 1 Gy fractions in an overall time of 4 weeks. CT scans were made weekly, immediately after treatment, and matched with the planning CT scan. Spatial variability of the tumor, as well as bladder volume and rectal diameter, were scored for each patient each week. RESULTS In 65% of patients, a part of the tumor appeared outside the planning target volume boundaries at least one time during the course of radiotherapy. No consistent relation of this variability with time was found. Bladder volumes and rectal diameters showed marked variability during the course of treatment. A large initial bladder volume and rectal diameter predicted a large volume variation and a large tumor spatial variability. CONCLUSION In this study, a margin of 1.5 to 2 cm seemed to be inadequate in 65% of the patients with respect to spatial variability. Bladder volume and rectal diameter were found to be predictive for spatial variability of a bladder tumor during concomitant boost radiotherapy.

Concomitant boost radiotherapy for muscle invasive bladder cancer

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.

The AMORE Protocol for Advanced-Stage and Recurrent Nonorbital Rhabdomyosarcoma in the Head-and-Neck Region of Children: A Radiation Oncology View

PURPOSE A multidisciplinary approach, consisting of consecutive Ablative Surgery, MOld technique with afterloading brachytherapy and immediate surgical REconstruction (AMORE) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. METHODS AND MATERIALS After macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. RESULTS Dose to the clinical target volume varied from 40 to 50 Gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of AMORE was 1.2-16.9 years (average, 6.5 years). Follow-up was 0.2-14.5 years (average, >5.5 years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. CONCLUSIONS The AMORE protocol yields good local control and overall survival rates, and side effects are acceptable.

Pulse Frequency in Pulsed Brachytherapy Based on Tissue Repair Kinetics

PURPOSE Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics. METHOD Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h. RESULTS The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant. CONCLUSION Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.

Brachytherapy as Part of the Multidisciplinary Treatment of Childhood Rhabdomyosarcomas of the Orbit

INTRODUCTION Rhabdomyosarcomas in the orbit form a major challenge in terms of cure without severe side effects in childhood cancer. Our specifically developed approach consists of applying brachytherapy to the tumor area using a mold. Analysis of its results for 20 patients was performed. METHODS AND MATERIALS Thirteen patients were referred for brachytherapy if complete remission was not reached after chemotherapy (Group I) and 7 in case of relapse (Group II). In total, 20 patients were treated between 1991 and 2007. Four were female and 16 male; their ages varied from 1.1 to 16.5 years, with an average of 8.5 years. After macroscopically radical tumor resection, molds with holes drilled to hold flexible catheters were placed into the orbit. The dose to the clinical target volume was 40-50 Gy. RESULTS Three patients of Group I and 1 patient of Group II developed local recurrence and underwent exenteration. The progression-free survival in Group I is 71.9% (95% CI 0.44-1.0), in Group II 85.7% (95% CI 0.60-1.0), the overall 5-year survival rate of the entire group is 92% (95% CI 0.76-1.0). During treatment, no serious side effects were observed. The late complications encountered in this series were cataract in 2 patients, 1 of whom also developed mild retinopathy. Two patients with ptosis needed surgical correction. No facial asymmetries or bone growth anomalies were observed. CONCLUSIONS This entire procedure of brachytherapy with a mold offers a tailor-made treatment for orbital rhabdomyosarcomas with only few signs of late toxicity.

Treatment of localized prostatic carcinoma using the transrectal ultrasound guided transperineal implantation technique

Treatment of localized prostate cancer by ultrasonically guided transperineal 125I implantation, in contrast to open 125I implantation, may allow for ideal distribution of the seeds and may therefore lead to better treatment results. 46 patients with localized prostatic carcinoma (T1-T2, G1-G3, N0, M0) have been treated since 1985, using this new technique. The longest follow-up is 64 months (median 30 months). The irradiation implantation dose to the prostate was 160 Gy. Assessed by ultrasonography an average prostate volume reduction of 20% was achieved at 6 months, increasing to 24% at 12 months, 39% at 24 months and 56% at 48 months. To evaluate response of the primary tumor systematic ultrasonically guided needle biopsies from the previous malignant prostate areas were performed in all patients every 6 months during follow-up. Tumor-negative biopsies were obtained in 33% of patients at 12 months, 40% at 24 months, progressively increasing to 50% at 48 months. Three patients developed distant metastases, and 6 died, of whom 1 patient due to prostate cancer. Morbidity from implantation has been low and the erectile function was preserved in all patients at 12 months postimplantation. The high percentage of tumor-positive biopsies during follow-up indicates that this technique fails to cure a significant proportion of patients.

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

BackgroundResults of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.MaterialIncluded are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).TreatmentGroup I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m2: 56 pts (standard).Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m2 d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.ResultsThe 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.ConclusionIn this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.

Brachytherapy with transperineal 125Iodine seeds for localized prostate cancer

Abstract 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 ≤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.

A comparison of inverse optimization algorithms for HDR/PDR prostate brachytherapy treatment planning

PURPOSE Graphical optimization (GrO) is a common method for high-dose-rate/pulsed-dose-rate (PDR) prostate brachytherapy treatment planning. New methods performing inverse optimization of the dose distribution have been developed over the past years. The purpose is to compare GrO and two established inverse methods, inverse planning simulated annealing (IPSA) and hybrid inverse treatment planning and optimization (HIPO), and one new method, enhanced geometric optimization-interactive inverse planning (EGO-IIP), in terms of speed and dose-volume histogram (DVH) parameters. METHODS AND MATERIALS For 26 prostate cancer patients treated with a PDR brachytherapy boost, an experienced treatment planner optimized the dose distributions using four different methods: GrO, IPSA, HIPO, and EGO-IIP. Relevant DVH parameters (prostate-V100%, D90%, V150%; urethra-D(0.1cm3) and D(1.0cm3); rectum-D(0.1cm3) and D(2.0cm3); bladder-D(2.0cm3)) were evaluated and their compliance to the constraints. Treatment planning time was also recorded. RESULTS All inverse methods resulted in shorter planning time (mean, 4-6.7 min), as compared with GrO (mean, 7.6 min). In terms of DVH parameters, none of the inverse methods outperformed the others. However, all inverse methods improved on compliance to the planning constraints as compared with GrO. On average, EGO-IIP and GrO resulted in highest D90%, and the IPSA plans resulted in lowest bladder D2.0cm3 and urethra D(1.0cm3). CONCLUSIONS Inverse planning methods decrease planning time as compared with GrO for PDR/high-dose-rate prostate brachytherapy. DVH parameters are comparable for all methods.

Improved tumour control probability with MRI-based prostate brachytherapy treatment planning

Abstract Backgroun. Due to improved visibility on MRI, contouring of the prostate is improved compared to CT. The aim of this study was to quantify the benefits of using MRI for treatment planning as compared to CT-based planning for temporary implant prostate brachytherapy. Material and methods. CT and MRI image data of 13 patients were used to delineate the prostate and organs at risk (OARs) and to reconstruct the implanted catheters (typically 12). An experienced treatment planner created plans on the CT-based structure sets (CT-plan) and on the MRI-based structure sets (MRI-plan). Then, active dwell-positions and weights of the CT-plans were transferred to the MRI-based structure sets (CT-planMRI-contours) and resulting dosimetric parameters and tumour control probabilities (TCPs) were studied. Results. For the CT-planMRI-contours a statistically significant lower target coverage was detected: mean V100 was 95.1% as opposed to 98.3% for the original plans (p < 0.01). Planning on CT caused cold-spots that influence the TCP. MRI-based planning improved the TCPs by 6–10%, depending on the parameters of the radiobiological model used for TCP calculation. Basing the treatment plan on either CT- or MRI-delineations does not influence plan quality. Conclusion. Evaluation of CT-based treatment planning by transferring the plan to MRI reveals underdosage of the prostate, especially at the base side. Planning on MRI can prevent cold-spots in the tumour and improves the TCP.