PSMA-PET guided dose-escalated volumetric arc therapy (VMAT) for newly diagnosed lymph node positive prostate cancer: Efficacy and toxicity outcomes at two years.

PURPOSE/OBJECTIVES: There are no published reports of prostate specific membrane antigen (PSMA) positron emission tomography (PET) guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) in newly diagnosed lymph node (LN) positive prostate cancer. We report early toxicity and efficacy outcomes with this approach. MATERIALS/METHODS: Patients with newly diagnosed high-risk prostate cancer were staged using PSMA PET, computed tomography (CT) and bone scans. Patients with LN positive-only metastases were offered curative therapy using 3 months androgen deprivation therapy (ADT) followed by DE-IMRT (using volumetric arc therapy), and 3 years adjuvant ADT. All patients had fiducial marker insertion, with privately insured patients having spacer hydrogel insertion. PET and prostate magnetic resonance imaging were fused with the planning CT. We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45Fx to bilateral elective pelvic LNs. RESULTS: In all, 46 patients were treated, with 83% Gleason 8-10, 67% T3/T4, median number of LNs 2 (range 1-6), and median PET-positive LN volume 1.14 cc (range 0.15-4.14). LNs were outside of standard contouring guidelines in 37% of patients. The mean PET-positive LN clinical target volume dose ranged from 73.3 to 85.9 Gy (median 83.6 Gy). With 24 months median follow-up, two year failure-free survival was 100%, and 2 year overall survival 95.7%. Acute grade 1 and 2 GI toxicity occurred in 48 and 11% of patients, and GU toxicity in 72 and 24%. Late grade 1, 2 and 3 GI toxicity occurred in 13, 2 and 0%, and GU toxicity 28, 13 and 4%. No toxicity was attributable to the high dose LN boost. CONCLUSIONS: PSMA PET-guided DE-IMRT up to 81 Gy to the prostate and involved LNs, and long term ADT, is a promising approach for newly diagnosed LN positive prostate cancer. LN contouring guidelines require re-evaluation in the era of PSMA PET imaging.

Late toxicities of prostate cancer radiotherapy with and without hydrogel SpaceAOR insertion.

INTRODUCTION: To investigate whether the implantation of a hydrogel spacer (SpaceOAR) reduces long-term rectal toxicity for prostate cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS: Patients with localised prostate cancer treated with 81 Gy in 45 fx of IMRT over 9 weeks were retrospectively compared: 65 patients with SpaceOAR and 56 patients without SpaceOAR. Planning aims restricted rectal doses to V40 Gy < 35%, V65 Gy < 17%, V75 Gy < 10%. Toxicities were evaluated between 3 months and 3 years after the completion of radiotherapy and were based on the common terminology criteria for adverse events (CTCAE) assessment tool for diarrhoea, haemorrhoids, faecal incontinence and proctitis. RESULTS: The cumulative incidence of low-grade diarrhoea (G1) was significantly higher in the non-SpaceOAR group (21.4% vs 6.2%; P = 0.016). The cumulative incidence of proctitis (grades G1 and G2) was also higher in the non-SpaceOAR group (26.7% vs 9.2%; P = 0.015); the cumulative incidence of G2 proctitis was higher in the latter group (P = 0.043). There were no differences between the treatment groups for cumulative incidences of faecal incontinence and/or haemorrhoids. Three years after IMRT, diarrhoea and proctitis were higher in the non-SpaceOAR group, without reaching statistical significance. This finding was unchanged after correcting for baseline symptoms. CONCLUSION: SpaceOAR is of benefit in reducing the cumulative incidence of low-grade diarrhoea and proctitis for up to 3 years after intensity-modulated radiotherapy.

Can a peri-rectal hydrogel spaceOAR programme for prostate cancer intensity-modulated radiotherapy be successfully implemented in a regional setting?

INTRODUCTION: The aim of this study was to investigate whether the implementation of a hydrogel spacer (SpaceOAR) programme for patients treated with 81 Gy prostate intensity-modulated radiotherapy (IMRT) in a regional setting can reduce rectal doses and toxicity. METHODS: In this retrospective study, 125 patients with localised prostate cancer treated between April 2014 (programme commencement) and June 2015 were compared: 65 with SpaceOAR (inserted by five different urologists) and 60 patients treated over the same time period without SpaceOAR. Patients were treated with 81 Gy in 45Fx of IMRT over 9 weeks. Planning aims included restricting rectal doses to V40 Gy < 35%, V65 Gy < 17%, V75 Gy < 10%. Acute toxicity was assessed weekly during radiotherapy and at 12 weeks. RESULTS: Rectal volume parameters were all significantly lower in the SpaceOAR group, with an associated reduction in acute diarrhoea (13.8% vs 31.7%). There were no significant differences in the very low rates of acute and late faecal incontinence or proctitis, however, there was a trend towards increased haemorrhoid rate in the SpaceOAR group (11.7% vs 3.1%, P = 0.09). CONCLUSION: A SpaceOAR programme in a regional setting with urologists performing low volumes of insertions (<1 per month on average) is of clinical benefit, and was associated with significantly lower radiation doses to the rectum and lower rates of acute diarrhoea.

Prostate intensity-modulated radiotherapy planning in seven mouse clicks: Development of a class solution for cancer.

AIM: The aim of the retrospective study was to develop a planning class solution for prostate intensity-modulated radiotherapy (IMRT) that achieved target and organs-at-risk (OAR) doses within acceptable departmental protocol criteria using the Monaco treatment planning system (Elekta-CMS Software, MO, USA). BACKGROUND: Advances in radiation therapy technology have led to a re-evaluation of work practices. Class solutions have the potential to produce highly conformal plans in a time-efficient manner. MATERIALS AND METHODS: Using data from intermediate and high risk prostate cancer patients, a stepwise quality improvement model was employed. Stage 1 involved the development of a broadly based treatment template developed across 10 patients. Stage 2 involved template refinement and clinical audit (n = 20); Stage 3, template review (n = 50) and Stage 4 an assessment of a revised template against the actual treatment plan involving 72 patients. RESULTS: The computer algorithm that comprised the Stage 4 template met clinical treatment criteria for 82% of patients. Minor template changes were required for a further 13% of patients. Major changes were required in 4%; one patient could not be assessed. The average calculation time was 13 min and involved seven mouse clicks by the planner. Thus, the new template met treatment criteria or required only minor changes in 95% of prostate patients; this is an encouraging result suggesting improvements in planning efficiency and consistency. CONCLUSION: It is feasible to develop a class solution for prostate IMRT using a stepwise quality improvement model which delivers clinically acceptable plans in the great majority of prostate cases.

Tangential intensity modulated radiation therapy (IMRT) to the intact breast.

INTRODUCTION: Inverse-planned intensity modulated radiation therapy (IP-IMRT) has potential benefits over other techniques for tangential intact breast radiotherapy. Possible benefits include increased homogeneity, faster planning time, less inter-planner variability and lower doses to organs at risk (OAR). We therefore conducted a pilot study of previously treated intact breast patients to compare the current forward-planned 'field-in-field' technique (FP-IMRT) with an IP-IMRT alternative. METHODS: The IP-IMRT plans of 20 patients were generated from a template created for the planning system. All patients were prescribed adjuvant whole breast radiotherapy using a hypofractionated regimen of 40.05 Gy in 15 fractions over 3 weeks. Plans were assessed based on visual inspection of coverage as well as statistical analysis and compared to the clinically acceptable FP-IMRT plans. Patients were planned retrospectively in Monaco 3.2® using a laterality-specific, tangential planning template. Minor adjustments were made as necessary to meet the planning criteria in the protocol. Dose coverage, maximums, homogeneity indices and doses to OAR were recorded. RESULTS: The IP-IMRT plans provided more consistent coverage (38.18 Gy vs. 36.08 Gy of D95; P = 0.005), a comparable though higher average maximum (D2 = 42.52 Gy vs. 42.08 Gy; P = 0.0001), more homogeneous plans (homogeneity index = 0.908 vs. 0.861; P = 0.01) and somewhat lower V20 heart and lung doses (0.11% vs. 0.89% for heart; 5.4% vs. 7.52% for lung) than FP-IMRT (P > 0.05). CONCLUSION: Clinically acceptable plans have been generated using the IP-IMRT templates in Monaco. Improvements in consistency and quality were seen when compared to the FP-IMRT plans. The template-based process is an efficient method to inversely plan IMRT for breast patients.

Use of a prospective cohort study in the development of a bladder scanning protocol to assist in bladder filling consistency for prostate cancer patients receiving radiation therapy.

INTRODUCTION: Evidence of variations in bladder filling effecting prostate stability and therefore treatment and side-effects is well established with intensity modulated radiation therapy (IMRT). This study aimed to increase bladder volume reproducibility for prostate radiation therapy by implementing a bladder scanning (BS) protocol that could assist patients' bladder filling at computed tomography (CT) simulation and treatment. METHODS: Based on a retrospective review of 524 prostate cancer patients, a bladder volume of 250-350 mL was adopted as 'ideal' for achieving planning dose constraints. A prospective cohort study was conducted to assess the clinical utility of measuring patients' bladder volumes at CT simulation using an ultrasound bladder scanner (Verathon 9400 BladderScan(®)). A revised bladder preparation protocol was utilised by a bladder scan group (BS) and a non-BS group followed the standard departmental bladder preparation protocol. Time and volume data for the BS group (n = 17) were compared with the non-BS group (n = 17). RESULTS: The BS cohort had a CT bladder volume range of 221-588 mL; mean 379 mL, SD 125 mL. The non-BS group had a larger range: 184-757 mL; mean 373 mL, SD 160 mL (P = 0.9171). There was a positive correlation between CT volume and BS volume in the BS group (r = 0.797; P = 0.0002) although BS volumes were smaller: range 160-420 mL; mean 251 mL; SD 91 mL; P < 0.0001). The maximum bladder volume receiving 50 Gy (V50) from the BS group was 46.4%, mean 24.5%. The maximum bladder V50 from the non-BS group was 50.9%, mean 27.3% (P = 0.5178). Treatment data from weekly cone beam CT scans were also compared over 6 weeks. They were assessed as being a pass if bladder and bowel requirements were acceptable. The BS group proceeded to treatment on the basis of a pass 92.7% of the time, whereas the pass rate for non-BS group was 75%; difference 17.7% (P < 0.0001). CONCLUSION: The BS is a useful tool for achieving consistent, appropriately sized bladder volumes in prostate cancer patients.

Testing the Assessment of New Radiation Oncology Technology and Treatments framework using the evaluation of post-prostatectomy radiotherapy techniques.

INTRODUCTION: We tested the ability of the Assessment of New Radiation Oncology Technology and Treatments framework to determine the clinical efficacy and safety of intensity-modulated radiation therapy (IMRT) compared with 3-dimensional radiation therapy (3DCRT) for post-prostatectomy radiation therapy (PPRT) to support its timely health economic evaluation. METHODS: Treatment plans produced using FROGG guidelines provided dosimetry parameters for both techniques at 64 Gy and 70 Gy and were also used to model early and late outcome probabilities. Clinical parameters were derived from early toxicity and quality of life patient data, systematic literature review and expert opinion. Dosimetry parameters were correlated with the measures of clinical efficacy and safety. RESULTS: Data from two patient cohorts (29 and 27 respectively) were collected within the project timeframe, providing evidence for acute toxicity and quality of life, and dosimetric comparisons. Relative rates of tumour control probability (TCP) and normal tissue control probability (NTCP) modelling were readily derived from the planning exercise and demonstrated advantages in uncomplicated TCP for IMRT over 3DCRT, predominantly due to normal tissue sparing. The safety of IMRT delivery was demonstrated with TCP uncompromised by IMRT protocol violations, which achieved rectal sparing only by reducing minimum target dose and coverage. CONCLUSION: Sources of desk-top and patient-based evidence were successfully used to demonstrate potential improved clinical efficacy and safety of applying dose escalation using IMRT instead of 3DCRT in PPRT.

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

INTRODUCTION: There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. METHODS: Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. RESULTS: Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. CONCLUSIONS: We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy.