Toxicity and Patient-Reported Outcomes of a Phase 2 Randomized Trial of Prostate and Pelvic Lymph Node Versus Prostate only Radiotherapy in Advanced Localised Prostate Cancer (PIVOTAL).

PURPOSE: To establish the toxicity profile of high-dose pelvic lymph node intensity-modulated radiation therapy (IMRT) and to assess whether it is safely deliverable at multiple centers. METHODS AND MATERIALS: In this phase 2 noncomparative multicenter trial, 124 patients with locally advanced, high-risk prostate cancer were randomized between prostate-only IMRT (PO) (74 Gy/37 fractions) and prostate and pelvic lymph node IMRT (P&P; 74 Gy/37 fractions to prostate, 60 Gy/37 fractions to pelvis). The primary endpoint was acute lower gastrointestinal (GI) Radiation Therapy Oncology Group (RTOG) toxicity at week 18, aiming to exclude a grade 2 or greater (G2+) toxicity-free rate of 80% in the P&P group. Key secondary endpoints included patient-reported outcomes and late toxicity. RESULTS: One hundred twenty-four participants were randomized (62 PO, 62 P&P) from May 2011 to March 2013. Median follow-up was 37.6 months (interquartile range [IQR], 35.4-38.9 months). Participants had a median age of 69 years (IQR, 64-74 years) and median diagnostic prostate-specific androgen level of 21.6 ng/mL (IQR, 11.8-35.1 ng/mL). At week 18, G2+ lower GI toxicity-free rates were 59 of 61 (96.7%; 90% confidence interval [CI], 90.0-99.4) for the PO group and 59 of 62 (95.2%; 90% CI, 88.0-98.7) for the P&P group. Patients in both groups reported similarly low Inflammatory Bowel Disease Questionnaire symptoms and Vaizey incontinence scores. The largest difference occurred at week 6 with 4 of 61 (7%) and 16 of 61 (26%) PO and P&P patients, respectively, experiencing G2+ toxicity. At 2 years, the cumulative proportion of RTOG G2+ GI toxicity was 16.9% (95% CI, 8.9%-30.9%) for the PO group and 24.0% (95% CI, 8.4%-57.9%) for the P&P group; in addition, RTOG G2+ bladder toxicity was 5.1% (95% CI, 1.7%-14.9%) for the PO group and 5.6% (95% CI, 1.8%-16.7%) for the P&P group. CONCLUSIONS: PIVOTAL demonstrated that high-dose pelvic lymph node IMRT can be delivered at multiple centers with a modest side effect profile. Although safety data from the present study are encouraging, the impact of P&P IMRT on disease control remains to be established.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

Intra-fraction motion of the prostate during treatment with helical tomotherapy.

BACKGROUND AND PURPOSE: To measure the geometric uncertainty resulting from intra-fraction motion and intra-observer image matching, for patients having image-guided prostate radiotherapy on TomoTherapy. MATERIAL AND METHODS: All patients had already been selected for prostate radiotherapy on TomoTherapy, with daily MV-CT imaging. The study involved performing an additional MV-CT image at the end of treatment, on 5 occasions during the course of 37 treatments. 54 patients were recruited to the study. A new formula was derived to calculate the PTV margin for intra-fraction motion. RESULTS: The mean values of the intra-fraction differences were 0.0mm, 0.5mm, 0.5mm and 0.0° for LR, SI, AP and roll, respectively. The corresponding standard deviations were 1.1mm, 0.8mm, 0.8mm and 0.6° for systematic uncertainties (Σ), 1.3mm, 2.0mm, 2.2mm and 0.3° for random uncertainties (σ). This intra-fraction motion requires margins of 2.2mm in LR, 2.1mm in SI and 2.1mm in AP directions. Inclusion of estimates of the effect of rotations and matching errors increases these margins to approximately 4mm in LR and 5mm in SI and AP directions. CONCLUSIONS: A new margin recipe has been developed to calculate margins for intra-fraction motion. This recipe is applicable to any measurement technique that is based on the difference between images taken before and after treatment.