Hypofractionated helical intensity-modulated radiotherapy of the prostate bed after prostatectomy with or without the pelvic lymph nodes - the PRIAMOS trial

BACKGROUND: While evidence on safety and efficacy of primary hypofractionated radiotherapy in prostate cancer is accumulating, data on postoperative hypofractionated treatment of the prostate bed and of the pelvic lymph nodes is still scarce. This phase II trial was initiated to investigate safety and feasibility of hypofractionated treatment of the prostate bed alone or with the pelvic lymph nodes. METHODS/DESIGN: A total of 80 prostate cancer patients with the indication for adjuvant radiotherapy will be enrolled, where 40 patients with a low risk of lymph node involvement (arm 1) and another 40 patients with a high risk of lymph node involvement (arm 2) will each receive 54 Gy in 18 fractions to the prostate bed. Arm 2 will be given 45 Gy to the pelvic lymph nodes additionally. Helical Tomotherapy and daily image guidance will be used. DISCUSSION: This trial was initiated to substantiate data on hypofractionated treatment of the prostate bed and generate first data on adjuvant hypofractionated radiotherapy of the pelvic lymph nodes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT0162071

Helical intensity-modulated Radiotherapy of the Pelvic Lymph Nodes with Integrated Boost to the Prostate Bed - Initial Results of the PLATIN 3 Trial

BACKGROUND: Adjuvant and salvage radiotherapy of the prostate bed are established treatment options for prostate cancer. While the benefit of an additional radiotherapy of the pelvic lymph nodes is still under debate, the PLATIN 3 prospective phase II clinical trial was initiated to substantiate toxicity data on postoperative IMRT of the pelvic lymph nodes and the prostate bed. METHODS: From 2009 to 2011, 40 patients with high-risk prostate cancer after prostatectomy with pT3 R0/1 M0 or pT2 R1 M0 or a PSA recurrence and either > 20% risk of lymph node involvement and inadequate lymphadenectomy or pN + were enrolled. Patients received two months of antihormonal treatment (AT) before radiotherapy. AT continuation was mandatory during radiotherapy and was recommended for another two years. IMRT of the pelvic lymph nodes (51.0 Gy) with a simultaneous integrated boost to the prostate bed (68.0 Gy) was performed in 34 fractions. PSA level, prostate-related symptoms and quality of life were assessed at regular intervals for 24 months. RESULTS: Of the 40 patients enrolled, 39 finished treatment as planned. Overall acute toxicity rates were low and no acute grade 3/4 toxicity occurred. Only 22.5% of patients experienced acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity. During follow-up, 10.0% late grade 2 GI and 5.0% late grade 2 GU toxicity occurred, and one patient developed late grade 3 proctitis and enteritis. After a median observation time of 24 months the PLATIN 3 trial has shown in 97.5% of all patients sufficient safety and thus met its prospectively defined aims. After a median of 24 months, 34/38 patients were free of a PSA recurrence. CONCLUSIONS: Postoperative whole-pelvis IMRT with an integrated boost to the prostate bed can be performed safely and without excessive toxicity. TRIAL REGISTRATION: Trial Numbers: ARO 2009–05, ClinicalTrials.gov: NCT01903408

Accelerated large volume irradiation with dynamic Jaw/Dynamic Couch Helical Tomotherapy

BACKGROUND: Helical Tomotherapy (HT) has unique capacities for the radiotherapy of large and complicated target volumes. Next generation Dynamic Jaw/Dynamic Couch HT delivery promises faster treatments and reduced exposure of organs at risk due to a reduced dose penumbra. METHODS: Three challenging clinical situations were chosen for comparison between Regular HT delivery with a field width of 2.5 cm (Reg 2.5) and 5.0 cm (Reg 5.0) and DJDC delivery with a maximum field width of 5.0 cm (DJDC 5.0): Hemithoracic Irradiation, Whole Abdominal Irradiation (WAI) and Total Marrow Irradiation (TMI). For each setting, five CT data sets were chosen, and target coverage, conformity, integral dose, dose exposure of organs at risk (OAR) and treatment time were calculated. RESULTS: Both Reg 5.0 and DJDC 5.0 achieved a substantial reduction in treatment time while maintaining similar dose coverage. Treatment time could be reduced from 10:57 min to 3:42 min / 5:10 min (Reg 5.0 / DJDC 5.0) for Hemithoracic Irradiation, from 18:03 min to 8:02 min / 8:03 min for WAI and to 18:25 min / 18:03 min for TMI. In Hemithoracic Irradiation, OAR exposure was identical in all modalities. For WAI, Reg 2.5 resulted in lower exposure of liver and bone. DJDC plans showed a small but significant increase of ∼ 1 Gy to the kidneys, the parotid glans and the thyroid gland. While Reg 5.0 and DJDC were identical in terms of OAR exposure, integral dose was substantially lower with DJDC, caused by a smaller dose penumbra. CONCLUSIONS: Although not clinically available yet, next generation DJDC HT technique is efficient in improving the treatment time while maintaining comparable plan quality

Intensity modulated or fractionated stereotactic reirradiation in patients with recurrent nasopharyngeal cancer

<p>Abstract</p> <p>Purpose</p> <p>To report our experience with intensity-modulated or stereotactic reirradiation in patients suffering from recurrent nasopharyngeal carcinoma</p> <p>Patients and Methods</p> <p>The records of 17 patients with recurrent nasopharygeal carcinoma treated by intensity-modulated (n = 14) or stereotactic (n = 3) reirradiation in our institution were reviewed. Median age was 53 years and most patients (n = 14) were male. The majority of tumors showed undifferentiated histology (n = 14) and infiltration of intracranial structures (n = 12). Simultaneous systemic therapy was applied in 8 patients. Initial treatment covered the gross tumor volume with a median dose of 66 Gy (50-72 Gy) and the cervical nodal regions with a median dose of 56 Gy (50-60 Gy). Reirradiation was confined to the local relapse region with a median dose of 50.4 Gy (36-64Gy), resulting in a median cumulative dose of 112 Gy (91-134 Gy). The median time interval between initial and subsequent treatment was 52 months (6-132).</p> <p>Results</p> <p>The median follow up for the entire cohort was 20 months and 31 months for survivors (10-84). Five patients (29%) developed isolated local recurrences and three patients (18%) suffered from isolated nodal recurrences. The actuarial 1- and 2-year rates of local/locoregional control were 76%/59% and 69%/52%, respectively. Six patients developed distant metastasis during the follow up period. The median actuarial overall survival for the entire cohort was 23 months, transferring into 1-, 2-, and 3-year overall survival rates of 82%, 44% and 37%. Univariate subset analyses showed significantly increased overall survival and local control for patients with less advanced rT stage, retreatment doses > 50 Gy, concurrent systemic treatment and complete response. Severe late toxicity (Grad III) attributable to reirradiation occurred in five patients (29%), particularly as hearing loss, alterations of taste/smell, cranial neuropathy, trismus and xerostomia.</p> <p>Conclusion</p> <p>Reirradiation with intensity-modulated or stereotactic techniques in recurrent nasopharyngeal carcinoma is feasible and yields encouraging results in terms of local control and overall survival in patients with acceptable toxicity in patients with less advanced recurrences. However, the achievable outcome is limited in patients with involvement of intracranial structures, emphasising the need for close monitoring after primary therapy.</p

The influence of fractionated radiotherapy on the stability of spinal bone metastases: a retrospective analysis from 1047 cases

Background: The effect of radiotherapy, in particular the application of different multi-fraction schedules in the management of unstable spinal bone metastases (SBM), is incompletely understood. This study aims to compare the radiological response regarding various dose and fractionation schedules of radiotherapy in the palliative treatment of SBM. Methods: We retrospectively assessed 1047 patients with osteolytic SBM, treated with palliative radiotherapy at our department between 2000 and 2015. Lung cancer (40.2%), breast (16.7%) and renal cancer (15.2%) were the most common solid tumors in this study. Different common multi-fraction regimen (5x4Gy, 10x3Gy, 14 × 2.5Gy and 20x2Gy) were compared with regard to radiological response and recalcification at 3 and 6 months after radiotherapy. The Taneichi score was used for classification of osteolytic SBM. Results: Median follow up was 6.3 months. The median overall survival (OS) in the short-course radiotherapy (SCR) group using less than 10 treatment fractions was 5.5 months vs. 9.5 months in the long-course radiotherapy (LCR) group using in excess of 10 fractions (log rank p &lt; .0001). Overall survival (OS) in the SCR group after 3 and 6 months was 66.8 and 49.1%, respectively vs 80.9 and 61.5%, respectively in the LCR group. 17.6% (n = 54/306) and 31.1% (n = 89/286) of unstable SBM were classified as stable in the SCR group at 3 and 6 months post radiotherapy, respectively (p &lt; .001 for both). In the LCR group, 24.1% (n = 28/116) and 34.2% (n = 38/111) of unstable SBM were stabilized after 3 and 6 months, respectively (p &lt; .001 for both). Conclusions: Our study shows no significant difference in stabilization achieving recalcification rates between multi-fraction schedules (SCR vs. LCR) in the palliative management of unstable SBM. Both groups with multi-fraction regimen demonstrate a stabilizing effect following 3 and 6 months after radiotherapy

Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer

Background: To report our experience with increased dose intensity-modulated radiation and concurrent systemic chemotherapy as definitive treatment of locally advanced esophageal cancer. Patients and methods: We analyzed 27 consecutive patients with histologically proven esophageal cancer, who were treated with increased-dose IMRT as part of their definitive therapy. The majority of patients had T3/4 and/or N1 disease (93%). Squamous cell carcinoma was the dominating histology (81%). IMRT was delivered in step-and-shoot technique in all patients using an integrated boost concept. The boost volume was covered with total doses of 56-60 Gy (single dose 2-2.14 Gy), while regional nodal regions received 50.4 Gy (single dose 1.8 Gy) in 28 fractions. Concurrent systemic therapy was scheduled in all patients and administered in 26 (96%). 17 patients received additional adjuvant systemic therapy. Loco-regional control, progression-free and overall survival as well as acute and late toxicities were retrospectively analyzed. In addition, quality of life was prospectively assessed according to the EORTC QLQs (QLQ-OG25, QLQ-H&N35 and QLQ-C30). Results: Radiotherapy was completed as planned in all but one patient (96%), and 21 patients received more than 80% of the planned concurrent systemic therapy. We observed ten locoregional failures, transferring into actuarial 1-, 2- and 3-year-locoregional control rates of 77%, 65% and 48%. Seven patients developed distant metastases, mainly to the lung (71%). The actuarial 1-, 2- and 3-year-disease free survival rates were 58%, 48% and 36%, and overall survival rates were 82%, 61% and 56%. The concept was well tolerated, both in the clinical objective examination and also according to the subjective answers to the QLQ questionnaire. 14 patients (52%) suffered from at least one acute CTC grade 3/4 toxicity, mostly hematological side effects or dysphagia. Severe late toxicities were reported in 6 patients (22%), mostly esophageal strictures and ulcerations. Severe side effects to skin, lung and heart were rare. Conclusion: IMRT with concurrent systemic therapy in the definitive treatment of esophageal cancer using an integrated boost concept with doses up to 60 Gy is feasible and yields good results with acceptable acute and late overall toxicity and low side effects to skin, lung and heart

Linear accelerator-based stereotactic fractionated photon radiotherapy as an eye-conserving treatment for uveal melanoma

Background: The purpose of this retrospective analysis is to analyze clinical outcome, visual acuity and enucleation rates after linear accelerator-based stereotactic fractionated photon radiotherapy for primary uveal melanoma. Methods: Twenty-four patients with primary uveal melanoma treated at the Department of Radiation and Oncology of the University Hospital Heidelberg between 1991 and 2015 were analyzed regarding survival and treatment-related toxicity including eye- and sight-preservation. Results: Photon radiotherapy (RT) offered good overall local control rates with a local progression-free survival (LPFS) of 82% after 5 years and a median LPFS of 5.5 years at a median follow-up time of 5.2 years. Gender had a significant impact on LPFS yielding a mean LPFS of 8.1 years for women and 8.7 years for men (p = 0.04). Of all local progressions, 80% occurred within the first 5 years after RT. In one case, enucleation as final therapy option was necessary. Enucleation-free survival (EFS) was related to the radiotherapy dose (p &lt; 0.0001). Thus, higher prescribed doses led to a significantly higher enucleation rate. T-stage had no significant impact on EFS, but affected the enucleation rate (p = 0.01). The overall survival (OS) rate was 100% after 2 years and 70% after 5 years with a median OS of 5.75 years. Age (p = 0.046), T stage (p = 0.019), local control rate (p = 0.041) and the time between diagnosis and the first radiation session (p = 0.01) had a significant effect on OS. Applied biologically effective dose (BED) did not significantly influence OS or PFS. A 2-year sight preservation rate of 75% could be achieved. In all patients, irradiation could be applied safely without any interruptions due to side effects. Six significant late toxicities with consequential blindness could be observed, making a secondary enucleation necessary in four patients. An impairment of visual acuity due to chronic optic nerve atrophy was identified in five patients within 2 years after treatment. Conclusions: Linear accelerator-based stereotactic fractionated photon radiotherapy is an effective method in the treatment of uveal melanoma with excellent local control rates and a 2-year vision retention rate comparable to brachytherapy (BRT) or proton beam radiotherapy, even available in small centers and easy to implement. Interdisciplinary decision making is necessary to guarantee best treatment for every patient

Correction of patient positioning errors based on in-line cone beam CTs: clinical implementation and first experiences

BACKGROUND: The purpose of the study was the clinical implementation of a kV cone beam CT (CBCT) for setup correction in radiotherapy. PATIENTS AND METHODS: For evaluation of the setup correction workflow, six tumor patients (lung cancer, sacral chordoma, head-and-neck and paraspinal tumor, and two prostate cancer patients) were selected. All patients were treated with fractionated stereotactic radiotherapy, five of them with intensity modulated radiotherapy (IMRT). For patient fixation, a scotch cast body frame or a vacuum pillow, each in combination with a scotch cast head mask, were used. The imaging equipment, consisting of an x-ray tube and a flat panel imager (FPI), was attached to a Siemens linear accelerator according to the in-line approach, i.e. with the imaging beam mounted opposite to the treatment beam sharing the same isocenter. For dose delivery, the treatment beam has to traverse the FPI which is mounted in the accessory tray below the multi-leaf collimator. For each patient, a predefined number of imaging projections over a range of at least 200 degrees were acquired. The fast reconstruction of the 3D-CBCT dataset was done with an implementation of the Feldkamp-David-Kress (FDK) algorithm. For the registration of the treatment planning CT with the acquired CBCT, an automatic mutual information matcher and manual matching was used. RESULTS AND DISCUSSION: Bony landmarks were easily detected and the table shifts for correction of setup deviations could be automatically calculated in all cases. The image quality was sufficient for a visual comparison of the desired target point with the isocenter visible on the CBCT. Soft tissue contrast was problematic for the prostate of an obese patient, but good in the lung tumor case. The detected maximum setup deviation was 3 mm for patients fixated with the body frame, and 6 mm for patients positioned in the vacuum pillow. Using an action level of 2 mm translational error, a target point correction was carried out in 4 cases. The additional workload of the described workflow compared to a normal treatment fraction led to an extra time of about 10–12 minutes, which can be further reduced by streamlining the different steps. CONCLUSION: The cone beam CT attached to a LINAC allows the acquisition of a CT scan of the patient in treatment position directly before treatment. Its image quality is sufficient for determining target point correction vectors. With the presented workflow, a target point correction within a clinically reasonable time frame is possible. This increases the treatment precision, and potentially the complex patient fixation techniques will become dispensable