Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: 5-Year Efficacy and Toxicity in the DELINEATE Trial.

PURPOSE: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. METHODS AND MATERIALS: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. RESULTS: Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). CONCLUSIONS: The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: Efficacy and Toxicity in the DELINEATE Trial.

PURPOSE: To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy. METHODS AND MATERIALS: DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate- and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic resonance imaging. Fifty-five patients were treated in cohort A, and 158 patients were treated in cohort B; the first 50 sequentially treated patients in cohort B were included in this planned analysis. The primary endpoint was late Radiation Therapy Oncology Group rectal toxicity at 1 year. Secondary endpoints included acute and late toxicity measured with clinician- and patient-reported outcomes at other time points and biochemical relapse-free survival for cohort A. Median follow-up was 74.5 months for cohort A and 52.0 months for cohort B. RESULTS: In cohorts A and B, 27% and 40% of patients, respectively, were classified as having National Comprehensive Cancer Network high-risk disease. The cumulative 1-year incidence of Radiation Therapy Oncology Group grade 2 or worse rectal and urinary toxicity was 3.6% and 0% in cohort A and 8% and 10% in cohort B, respectively. There was no reported late grade 3 rectal toxicity in either cohort. Within cohort A, 4 of 55 (7%) patients had biochemical relapse. CONCLUSIONS: Delivery of a simultaneous integrated boost to intraprostatic dominant nodules is feasible in prostate radiation therapy using standard and moderately hypofractionated regimens, with rectal and genitourinary toxicity comparable to contemporary series without an intraprostatic boost.

Functional magnetic resonance: biomarkers of response in breast cancer.

Functional magnetic resonance (MR) encompasses a spectrum of techniques that depict physiological and molecular processes before morphological changes are visible on conventional imaging. As understanding of the pathophysiological and biomolecular processes involved in breast malignancies evolves, newer functional MR techniques can be employed that define early predictive and surrogate biomarkers for monitoring response to chemotherapy. Neoadjuvant chemotherapy is increasingly used in women with primary breast malignancies to down-stage the tumour and enable successful breast conservation surgery. It also plays a role in the treatment of undetected micrometastases. Cardinal physiological features of tumours that occur as a result of interactions between cancer cells, stromal cells and secreted factors and cytokines and how they change with treatment provide the opportunity to detect changes in the tumour microenvironment prior to any morphological change. Through sequential imaging, tumour response can be assessed and non-responders can be identified early to enable alternative therapies to be considered. This review summarises the functional magnetic resonance biomarkers of response in patients with breast cancer that are currently available and under development. We describe the current state of each biomarker and explore their potential clinical uses and limitations in assessing treatment response. With the aid of selected interesting cases, biomarkers related to dynamic contrast-enhanced MRI, diffusion-weighted MRI, T2*/BOLD and MR spectroscopy are described and illustrated. The potential of newer approaches, such as MR elastography, are also reviewed.