Yousef Najafi

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers

PurposeTo evaluate PTV margins for hypofractionated IGRT of prostate comparing kV/kV imaging or CBCT.Patients and methodsBetween 2009 and 2012, 20 patients with low- (LR), intermediate- (IR) and high-risk (HR) prostate cancer were treated with VMAT in supine position with fiducial markers (FM), endorectal balloon (ERB) and full bladder. CBCT’s and kV/kV imaging were performed before and additional CBCT’s after treatment assessing intra-fraction motion. CTVP for 5 patients with LR and CTVPSV for 5 patients with IR/HR prostate cancer were contoured independently by 3 radiation oncologists using MRI. The van Hark formula (PTV margin =2.5Σ +0.7σ) was applied to calculate PTV margins of prostate/seminal vesicles (P/PSV) using CBCT or FM.Results172 and 52 CBCTs before and after RT and 507 kV/kV images before RT were analysed. Differences between FM in CBCT or in planar kV image pairs were below 1 mm. Accounting for both random and systematic uncertainties anisotropic PTV margins were 5-8 mm for P (LR) and 6-11 mm for PSV (IR/HR). Random uncertainties like intra-fraction and inter-fraction (setup) uncertainties were of similar magnitude (0.9-1.4 mm). Largest uncertainty was introduced by CTV delineation (LR: 1-2 mm, IR/HR: 1.6-3.5 mm). Patient positioning using bone matching or ERB-matching resulted in larger PTV margins.ConclusionsFor IGRT CBCT or kV/kV-image pairs with FM are interchangeable in respect of accuracy. Especially for hypofractionated RT, PTV margins can be kept in the range of 5 mm or below if stringent daily IGRT, ideally including prostate tracking, is applied. MR-based CTV delineation optimization is recommended.

Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

PURPOSE Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. METHODS AND MATERIALS A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. RESULTS Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. CONCLUSIONS The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

Follow up after IMRT in oral cavity cancer: update.

PurposeExcept for early stages (T1/2 N0), the prognosis for patients with oral cavity cancer (OCC) is known to be worse than for those with pharyngeal carcinoma. While definitive intensity modulated radiation therapy (IMRT)-chemotherapy affords loco-regional control rates (LRC) of approximately 80% in advanced pharyngeal cancer, corresponding rates are reported to be much lower for OCC. The aim of this work was to evaluate loco-regional disease control and overall survival (OAS) in a relatively large OCC patient cohort treated in the IMRT era.Methods and materialsBetween October 2002 and June 2011, 160 OCC patients were treated with curative intention IMRT at our department. 122 patients (76%) were referred with primary disease and 38 patients (24%) with a recurrent OCC at least 3 months after surgery alone. Definitive IMRT was performed in 44/160 patients (28%), whilst 116 patients underwent previous surgery. Simultaneous systemic therapy was administered in 72%.ResultsPatients with postoperative IMRT (+/−systemic therapy) with R0-1 status (n = 99) reached significantly higher LRC/OAS rates than patients following IMRT for macroscopic disease (n = 61), with 84%/80% versus 38%/33% at 3 years, respectively (p < 0.0001). This was found in patients treated for initial, as well as recurrent, disease. Less than 2% persisting grade 3/4 late effects were observed.ConclusionsIMRT for R0-1 situations translated into a highly significant superior LRC and OAS compared to the IMRT cohort treated for macroscopic disease. Treatment was well tolerated.

The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma.

Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations.

Importance and outcome relevance of central pathology review in prostatectomy specimens: data from the SAKK 09/10 randomized trial on prostate cancer.

To conduct a central pathology review within a randomized clinical trial on salvage radiation therapy (RT) in the presence of biochemical recurrence after prostatectomy to assess whether this results in changes in histopathological prognostic factors, such as Gleason score.

The effect of endorectal balloon on anorectal dose during postoperative volumetric arc radiotherapy of prostate cancer

PURPOSE To evaluate the impact of endorectal balloon (ERB) on anorectal dose during postoperative VMAT of prostate cancer. METHODS In ten patients referred for salvage radiotherapy CTs were obtained without ERB and with air-filled ERB of 50ml and 100ml. CTs were repeated weekly (4-6 control CTs) and registered to the respective planning CT. For each planning CT, a VMAT plan was made with defined anorectal dose constraints and propagated on the respective control CTs. The dose volumes V40Gy, V60Gy and V65Gy of the rectal and anal wall (Rwall and Awall, respectively) and the ERB position were obtained from each plan. RESULTS In plans with ERB, the mean Rwall dose volumes V40Gy, V60Gy and V65Gy were higher by 8%, 5% and 2% (ERB 50ml) and 2%, 3% and 3% (ERB 100ml) in comparison to plans without ERB. The respective Awall dose volume differences were 2%, 0%, -1% (ERB 50ml), and -3%, -2%, -2% (ERB 100ml). The dose volume variability of the Rwall was comparable with and without ERB, but was slightly reduced by ERB for the Awall. The mean ERB position variability was >2mm in anterior-posterior and inferior-superior directions. CONCLUSION The use of ERB during post-operative VMAT has no advantages for anorectal dose.

POSTER: CLINICAL TRACK: GENITOURINARY (PROSTATE INCLUDED)PO-0723: Stability of dose to the rectum during salvage radiotherapy with endorectal balloon after prostatectomy

Purpose/Objective: High dose image guided radiotherapy (IGRT) using prostate fiducials is standard of care for low and intermediate risk patients. However, high risk patients also benefit from prophylactic intensity modulated radiotherapy (IMRT) to the lymph nodes. The prostate can move independently to the pelvic nodes, therefore the safety of combining fiducial IGRT and pelvic nodal IMRT in high risk patients is uncertain. We aim to ascertain the dosimetric impact of employing fiducial-based hybrid IG-IMRT on the lymph node planning target volume (PTV). Materials and Methods: Thirty consecutive IMRT prostate and pelvic lymph node dosimetric plans were retrospectively reviewed after recalculation with incremental 1mm isocentre movements in all directions up to 10mm. In our centre, all IGRT images and shifts are recorded creating a population based database. Combining this database and the dosimetric data we calculated the overall risk of failing to maintain the following lymph node PTV statistics with fiducial IG-IMRT: PTV receiving > 99% of target dose (V99%) > 90%, PTV receiving > 95% of target dose (V95%) > 95% PTV receiving > 50% of target dose (V50%) > 100%. Results: Shifts in the left, right, and anterior directions do not have a significant impact on dose delivery with less than 0.25% risk of PTV coverage failure. Shifts posteriorly have the largest impact on dose but this still has less than 1% risk of failing PTV coverage. Conclusions: The risk of failing lymph node PTV coverage is very low with IG-IMRT and therefore we recommend adopting IG-IMRT in high risk prostate cancer patients receiving prophylactic lymph node irradiation. This will allow a reduction in CTV to PTV margins to the prostate volume leading to reduced toxicity and scope for dose escalation.