Aldo Rolfo

Online Adaptive Radiotherapy for Muscle-Invasive Bladder Cancer: Results of a Pilot Study

PURPOSE To determine the advantages and disadvantages of daily online adaptive image-guided radiotherapy (RT) compared with conventional RT for muscle-invasive bladder cancer. METHODS AND MATERIALS Twenty-seven patients with T2-T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided RT using cone-beam computed tomography (CBCT). From day 1 daily soft tissue-based isocenter positioning was performed using CBCT images acquired before treatment. Using a composite of the initial planning CT and the first five daily CBCT scans, small, medium, and large adaptive plans were created. Each of these adaptive plans used a 0.5-cm clinical target volume (CTV) to planning target volume expansion. For Fractions 8-32, treatment involved daily soft tissue-based isocenter positioning and selection of suitable adaptive plan of the day. Treating radiation therapists completed a credentialing program, and one radiation oncologist performed all the contouring. Comparisons were made between adaptive and conventional treatment on the basis of CTV coverage and normal tissue sparing. RESULTS All 27 patients completed treatment per protocol. Bladder volume decreased with time or fraction number (p < 0.0001). For the adaptive component (Fractions 8-32) the small, medium, large, and conventional plans were used in 9.8%, 49.2%, 39.5%, and 1.5% of fractions, respectively. For the adaptive strategy, 2.7% of occasions resulted in a CTV V95 <99%, compared with 4.8% of occasions for the conventional approach (p = 0.42). Mean volume of normal tissue receiving a dose >45 Gy was 29% (95% confidence interval, 24-35%) less with adaptive RT compared with conventional RT. The mean volume of normal tissue receiving >5 Gy was 15% (95% confidence interval, 11-18%) less with adaptive RT compared with conventional RT. CONCLUSIONS Online adaptive radiotherapy is feasible in an academic radiotherapy center. The volume of normal tissue irradiated can be significantly smaller without reducing CTV coverage.

Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy

BackgroundImage-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically.MethodsBetween 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74Gy in 37 fractions, to 78Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment.ResultsIn the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference.ConclusionsIn this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.

Offline adaptive radiotherapy for bladder cancer using cone beam computed tomography

We investigated if an adaptive radiotherapy approach based on cone beam CT (CBCT) acquired during radical treatment was feasible and resulted in improved dosimetric outcomes for bladder cancer patients compared to conventional planning and treatment protocol. A secondary aim was to compare a conventional plan with a theoretical online process where positioning is based on soft tissue position on a daily basis and treatment plan choice is based on bladder size. A conventional treatment plan was derived from a planning CT scan in the radical radiotherapy of five patients with muscle invasive bladder cancer. In this offline adaptive protocol using CBCT, the patients had 10 CBCT: daily CBCT for the first five fractions and then CBCT scan on a weekly basis. The first five daily CBCT in each patient were used to create a single adaptive plan for treatment from fraction eight onwards. A different process using the planning CT and the first five daily CBCT was used to create small, average and large bladder volumes, giving rise to small, average and large adaptive bladder treatment plans, respectively. In a retrospective analysis using the CBCT scans, we compared the clinical target volume (CTV) coverage using three protocols: (i) conventional; (ii) offline adaptive; and (iii) online adaptive with choice of ‘plan of the day’. Daily CBCT prolonged treatment time by an average of 7 min. Two of the five patients demonstrated such variation in CTV that an offline adaptive plan was used for treatment after the first five CBCT. Comparing the offline adaptive plan with the conventional plan, the CTV coverage improved from a minimum of 60.1 to 94.7% in subsequent weekly CBCT. Using the CBCT data, modelling an online adaptive protocol showed that coverage of the CTV by the 95% prescribed dose line by small, medium and large adaptive plans were 34.9, 67.4 and 90.7% of occasions, respectively. More normal tissue was irradiated using a conventional CTV to planning target volume margin (1.5 cm) compared to an online adaptive process (0.5 cm). An offline adaptive strategy improves dose coverage in certain patients to the CTV and results in a higher conformity index compared to conventional planning. Further research in online adaptive radiation therapy for bladder cancer is indicated.

Adaptive radiotherapy for bladder cancer reduces integral dose despite daily volumetric imaging.

We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging.

Credentialing of radiotherapy centres for a clinical trial of adaptive radiotherapy for bladder cancer (TROG 10.01).

BACKGROUND Daily variations in bladder filling make conformal treatment of bladder cancer challenging. On-line adaptive radiotherapy with a choice of plans has been demonstrated to reduce small bowel irradiation in single institution trials. In order to support a multicentre feasibility clinical trial on adaptive radiotherapy for bladder cancer (TROG 10.01) a credentialing programme was developed for centres wishing to participate. METHODS The credentialing programme entails three components: a facility questionnaire; a planning exercise which tests the ability of centres to create three adaptive plans based on a planning and five cone beam CTs; and a site visit during which image quality, imaging dose and image guidance procedures are assessed. Image quality and decision making were tested using customised inserts for a Perspex phantom (Modus QUASAR) that mimic different bladder sizes. Dose was assessed in the same phantom using thermoluminescence dosimetry (TLD). RESULTS All 12 centres participating in the full credentialing programme were able to generate appropriate target volumes in the planning exercise and identify the correct target volume and position the bladder phantom in the phantom within 3mm accuracy. None of the imaging doses exceeded the limit of 5 cGy with a CT on rails system having the lowest overall dose. CONCLUSION A phantom mimicking the decision making process for adaptive radiotherapy was found to be well suited during site visits for credentialing of centres participating in a clinical trial of adaptive radiotherapy for bladder cancer. Combined with a planning exercise the site visit allowed testing the ability of centres to create adaptive treatment plans and make appropriate decisions based on the volumetric images acquired at treatment.

Bladder cancer radiotherapy margins: a comparison of daily alignment using skin, bone or soft tissue.

AIMS To determine the clinical target volume (CTV) to planning target volume (PTV) margins required for bladder coverage when using skin or bony or soft tissue matching on a daily basis. MATERIALS AND METHODS Twenty-seven patients with T2-T4 transitional cell carcinoma of the bladder were treated with daily online adaptive image-guided radiotherapy using cone beam computed tomography. All daily CTVs were contoured by a single observer. A retrospective comparison of coverage of the bladder CTV using skin, bone and soft tissue matching was conducted. RESULTS With the skin set-up, bladder CTV coverage with a margin of 0.5, 1.0, 1.5, 2.0 and 2.5 cm was 0, 19, 56, 93 and 96%, respectively. For the daily set-up based on bone, the respective coverage was 0, 41, 63, 89 and 96%. For soft tissue set-up based on the geometric centre of the bladder, coverage was 52, 89, 96, 100 and 100%, respectively. CONCLUSIONS Based on coverage of the CTV, the required CTV to PTV margins are smaller for the daily online soft tissue set-up compared with skin or bone.

The dosimetric consequences of anatomic changes in head and neck radiotherapy patients

Introduction: To investigate anatomical response‐related changes in the head and neck region during a course of radical radiotherapy and their impact on the planned dosimetry.

The effect of an intensive nutritional program on daily set-up variations and radiotherapy planning margins of head and neck cancer patients

This is a prospective case‐control study to assess nutritional supplementation in limiting weight loss and its impact on daily set‐up variations and planning target volume (PTV) margins in head and neck (H&N) radiotherapy (RT). Twenty sequential H&N patients were recruited for this study. Ten patients had a percutaneous endoscopic gastrostomy (PEG) tube inserted prior to RT and 10 did not. PEG use was determined by departmental guidelines for patients considered at high risk for weight loss. Daily 2D electronic portal images were taken for orthogonal verification. Set‐up variations were determined for both PEG and non‐PEG patients by calculating systematic (Σ) and random (σ) errors, and PTV margins were derived. PEG patients lost less weight (P = 0.04) over the course of RT and had a reduction in set‐up variation in the superior–inferior (SI) and anterior–posterior (AP) planes compared to those without. Mean correctional shifts in mm (range) for PEG patients were: Right–Left (RL) 0.1 (−1.9–2.1), SI −1.7 (−2.9–0.0), AP −0.4 (−2.0–0.8), and for non‐PEG patients were: RL −0.2 (−2.7–1.3), SI −1.3 (−3.1–1.0), AP 0.4 (−1.5–2.8). The adapted PTV margins (mm) in the RL, SI and AP planes, respectively, for PEG patients were 4.1, 3.3 and 3.6, and for non‐PEG were 3.9, 4.9 and 4.8. Intensive enteral support maintained weight stability in H&N patients considered at risk of weight loss during RT and this was associated with reduced set‐up variation.

Benchmarking dosimetric quality assessment of prostate intensity-modulated radiotherapy.

PURPOSE To benchmark the dosimetric quality assessment of prostate intensity-modulated radiotherapy and determine whether the quality is influenced by disease or treatment factors. PATIENTS AND METHODS We retrospectively analyzed the data from 155 consecutive men treated radically for prostate cancer using intensity-modulated radiotherapy to 78 Gy between January 2007 and March 2009 across six radiotherapy treatment centers. The plan quality was determined by the measures of coverage, homogeneity, and conformity. Tumor coverage was measured using the planning target volume (PTV) receiving 95% and 100% of the prescribed dose (V(95%) and V(100%), respectively) and the clinical target volume (CTV) receiving 95% and 100% of the prescribed dose. Homogeneity was measured using the sigma index of the PTV and CTV. Conformity was measured using the lesion coverage factor, healthy tissue conformity index, and the conformity number. Multivariate regression models were created to determine the relationship between these and T stage, risk status, androgen deprivation therapy use, treatment center, planning system, and treatment date. RESULTS The largest discriminatory measurements of coverage, homogeneity, and conformity were the PTV V(95%), PTV sigma index, and conformity number. The mean PTV V(95%) was 92.5% (95% confidence interval, 91.3-93.7%). The mean PTV sigma index was 2.10 Gy (95% confidence interval, 1.90-2.20). The mean conformity number was 0.78 (95% confidence interval, 0.76-0.79). The treatment center independently influenced the coverage, homogeneity, and conformity (all p < .0001). The planning system independently influenced homogeneity (p = .038) and conformity (p = .021). The treatment date independently influenced the PTV V(95%) only, with it being better at the start (p = .013). Risk status, T stage, and the use of androgen deprivation therapy did not influence any aspect of plan quality. CONCLUSION Our study has benchmarked measures of coverage, homogeneity, and conformity for the treatment of prostate cancer using IMRT. The differences seen between centers and planning systems and the coverage deterioration over time highlight the need for every center to determine their own benchmarks and apply clinical vigilance with respect to maintaining these through quality assurance.

Toxicity and Long-Term Outcomes of Dose-Escalated Intensity Modulated Radiation Therapy to 74Gy for Localised Prostate Cancer in a Single Australian Centre

Purpose To report the toxicity and long-term outcomes of dose-escalated intensity-modulated radiation therapy (IMRT) for patients with localised prostate cancer. Methods and Materials From 2001 to 2005, a total of 125 patients with histologically confirmed T1-3N0M0 prostate cancer were treated with IMRT to 74Gy at the Austin Health Radiation Oncology Centre. The median follow-up was 5.5 years (range 0.5–8.9 years). Biochemical prostate specific antigen (bPSA) failure was defined according to the Phoenix consensus definition (absolute nadir + 2ng/mL). Toxicity was scored according to the RTOG/EORTC criteria. Kaplan-Meier analysis was used to calculate toxicity rates, as well as the risks of bPSA failure, distant metastases, disease-specific and overall survival, at 5 and 8-years post treatment. Results All patients completed radiotherapy without any treatment breaks. The 8-year risks of ≥ Grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 6.4% and 5.8% respectively, and the 8-year risks of ≥ Grade 3 GU and GI toxicity were both < 0.05%. The 5 and 8-year freedom from bPSA failure were 76% and 58% respectively. Disease-specific survival at 5 and 8 years were 95% and 91%, respectively, and overall survival at 5 and 8 years were 90% and 71%, respectively. Conclusions These results confirm existing international data regarding the safety and efficacy of dose-escalated intensity-modulated radiation therapy for localised prostate cancer within an Australian setting.