Hansjoerg Vees

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

Abstract Background. Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. Material and methods. From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48–82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. Results. After a median follow-up of 31 months (range, 9–89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15–0.93). Conclusion. Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study

BackgroundA study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT.MethodsPlans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (DMax) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI90) parameters.ResultsTumor coverage (GTV and PTV) was improved with RA (V95% 92.6 ± 7.9 and 83.7 ± 3.3%), when compared to IMRT (V95% 88.6 ± 10.8 and 77.2 ± 2.2%). The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 ± 10.5%) and better for the PTV (V95%85.6 ± 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 ± 3.0 and 38.0 ± 25.3%) and IMPT (3.9 ± 2.7 and 25.1 ± 21.1%), when compared to IMRT (9.8 ± 5.3 and 60.7 ± 41.7%). CI90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photons techniques.ConclusionRA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk.

Small cell carcinoma of the urinary bladder: A retrospective, multicenter rare cancer network study of 107 patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Impact of 18F-FDG PET/CT on target volume delineation in recurrent or residual gynaecologic carcinoma

BackgroundTo evaluate the impact of 18F-FDG PET/CT on target volume delineation in gynaecological cancer.MethodsF-FDG PET/CT based RT treatment planning was performed in 10 patients with locally recurrent (n = 5) or post-surgical residual gynaecological cancer (n = 5). The gross tumor volume (GTV) was defined by 4 experienced radiation oncologists first using contrast enhanced CT (GTVCT) and secondly using the fused 18F-FDG PET/CT datasets (GTVPET/CT). In addition, the GTV was delineated using the signal-to-background (SBR) ratio-based adaptive thresholding technique (GTVSBR). Overlap analysis were conducted to assess geographic mismatches between the GTVs delineated using the different techniques. Inter- and intra-observer variability were also assessed.ResultsThe mean GTVCT (43.65 cm3) was larger than the mean GTVPET/CT (33.06 cm3), p = 0.02. In 6 patients, GTVPET/CT added substantial tumor extension outside the GTVCT even though 90.4% of the GTVPET/CT was included in the GTVCT and 30.2% of the GTVCT was found outside the GTVPET/CT. The inter- and intra-observer variability was not significantly reduced with the inclusion of 18F-FDG PET imaging (p = 0.23 and p = 0.18, respectively). The GTVSBR was smaller than GTVCT p ≤ 0.005 and GTVPET/CT p ≤ 0.005.ConclusionsThe use of 18F-FDG PET/CT images for target volume delineation of recurrent or post-surgical residual gynaecological cancer alters the GTV in the majority of patients compared to standard CT-definition. The use of SBR-based auto-delineation showed significantly smaller GTVs. The use of PET/CT based target volume delineation may improve the accuracy of RT treatment planning in gynaecologic cancer.

Long-term Results of a Comparative PET/CT and PET/MRI Study of 11 C-Acetate and 18 F-Fluorocholine for Restaging of Early Recurrent Prostate Cancer

Purpose The aims of this study were to assess the intraindividual performance of 18F-fluorocholine (FCH) and 11C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management. Methods Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA] ⩽3 ng/mL), primary radiotherapy (n = 8, prostate-specific antigen ⩽5 ng/mL), or radical prostatectomy + salvage radiotherapy (n = 15) underwent ACE and FCH PET-CT (n = 29) or PET-MRI (n = 4) studies in a randomized sequence 0 to 21 days apart. Results The detection rate for ACE was 66% and for FCH was 60%. Results were concordant in 79% of the cases (26/33) and discordant in 21% (retroperitoneal, n = 5; pararectal, n = 1; and external iliac nodes, n = 1). After a median FU of 41 months (n = 32, 1 patient lost to FU), the site of relapse was correctly identified by ACE and FCH in 53% (17/32) and 47% (15/32) of the patients, respectively (2 M1a patients ACE+/FCH−), whereas in 6 of 32 patients the relapse was not localized. Treatment approach was changed in 11 (34.4%) of 32 patients and 9 (28%) of 32 patients restaged with ACE and FCH PET, respectively. Conclusions In early recurrent PCa, ACE and FCH showed minor discrepancies, limited to nodal staging and mainly in the retroperitoneal area, with true positivity of PET findings confirmed in half of the cases during FU. Treatment approach turned out to be influenced by ACE or FCH PET studies in one third of the patients.

First year experience with IORT for breast cancer at the Geneva University Hospitals

Purpose: The Breast Centre at the Geneva University Hospitals implemented guidelines for breast cancer intraoperative radiotherapy (IORT) in 2012. The present study evaluates early breast and skin toxicities observed during the first year of the implementation. Material and methods: From February 2012 to January 2013, 52 women received IORT for primary breast cancer treated with conservative surgery. IORT was delivered with the Intrabeam ® system. The prescribed dose was 20 Gy at the applicator’s surface. No further radiation was to be given according to the following criteria: age ≥50 years old, histopathology of invasive ductal, mucinous, tubular, medullar or colloid carcinoma, unifocal tumor, absence of lymphovascular invasion (LVI), absence of extensive in situ component, tumor size ≤30 mm, pathological nodal status pN0 by sentinel node biopsy or pN1mi by axillary dissection, and clear resection margins ≥2 mm. If the criteria were not met, additional whole breast radiotherapy (WBRT) to an equivalent dose of 50 Gy in 2-Gy fractions was to be given post-operatively. Toxicity grades were based on LENT-SOMA scoring tables. Results: IORT was given as exclusive radiation therapy in 34 (65%) patients, whereas 18 (35%) patients received an additional hypofractionated WBRT of 40-47.25 Gy in 15-21 fractions, one of whom further received after IORT-WBRT an additional electron boost of 13.5 Gy to the tumor bed in 6 fractions. At 1-month post-IORT, no heart toxicity was recorded. Six (11.5%) patients presented grade 2 lung symptoms. Breast/skin most frequent toxicities were seroma, grade 3 in 13 of 52 (25%) patients. One patient had a wound dehiscence requiring suture, and one patient had hematoma after immediate bilateral breast reconstruction with implants. Regarding the 18 patients who received additional WBRT, subsequent reevaluation after the WBRT found no heart toxicity, grade 1 lung symptoms in 1 (5%) patient, and grade 3 breast and skin toxicity in 2 (11%) patients (1 persistent seroma and 1 skin dryness). The breast and skin toxicity observed in patients after additional WBRT was not significantly increased as compared with the toxicity earlier observed after IORT, P=0.631. Conclusions: Early evaluation of IORT found mild to moderate breast and skin toxicity. Toxicity was not significantly increased in patients receiving additional WBRT.