Carpe Diem: Making the Most of Plan-of-the-Day for Cervical Cancer Radiation Therapy.

PURPOSE: Radiation therapy is the key treatment for locally advanced cervical cancer. Organ motion presents a challenge to accurate targeting of external beam radiation therapy. The plan-of-the-day (PotD) adaptive approach is therefore an attractive option. We present our experience and the procedural steps required to implement PotD for cervix cancer. METHODS AND MATERIALS: We reviewed relevant studies on organ motion and adaptive radiation therapy identified through a literature search and cross referencing. These included 10 dosimetric and 3 quality of life studies directly assessing the PotD approach to radiation therapy in cervix cancer. RESULTS: Studies show improvements in target coverage and reduction of dose received by normal tissues and suggest improved toxicity. Clinical implementation of PotD has been slow because of a number of difficulties and uncertainties, which we discuss with the aim of helping teams to implement PotD at their center. CONCLUSIONS: The PotD approach improves dosimetry and may improve toxicity. We describe a framework to assist with practical implementation.

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.

Evaluation of organ motion-based robust optimisation for VMAT planning for breast and internal mammary chain radiotherapy.

AIMS: In patients undergoing locoregional radiotherapy (RT) for breast cancer including the internal mammary chain (IMC), VMAT has been shown to be superior to tangential-field radiotherapy in terms of target coverage and minimising dose to heart and lungs. In this study we describe and validate organ motion-based robust optimisation for generating breast and locoregional lymph node VMAT plans that are robust to inter-fractional changes. MATERIALS AND METHODS: In this retrospective study of five patients with left-sided breast cancer requiring locoregional breast radiotherapy including the IMC, non-robust plans were generated in the nominal scenario (planning-CT) and corresponding robust plans were created by optimising over a range of simulated CTs representing worst-case scenario shape changes to the breast. Both plans were re-calculated on CBCT images (n = 67) acquired prior to RT to generate estimates of delivered fractional dose. Plan robustness to inter-fractional changes was assessed in terms of the estimated target coverage and OAR dose. RESULTS: Organ motion-based robust optimisation was able to generate clinically acceptable treatment plans in the nominal scenario on the planning CT with no significant differences to OAR dose between the robust and non-robust planning techniques. All plans (robust and non-robust) achieved the mandatory target coverage requirements. Estimates of delivered dose demonstrated a significant improvement in breast target coverage for the robust plans compared to non-robust plans. For the breast CTV, 92% of the robust plans achieved the optimal D98% > 95% clinical goal as compared to 71% of the non-robust plans (p < 0.01). 94% of robust plans achieved acceptable superficial breast coverage, as compared to 55% for the non-robust technique. CONCLUSIONS: Organ motion-based robust optimisation VMAT is able to produce clinically acceptable organ-at-risk sparing plans for locoregional breast radiotherapy (including the IMC) that are robust to inter-fractional changes, therefore reducing the likelihood of reactive adaptive re-planning.

Dose prescription with spatial uncertainty for peripheral lung SBRT.

Current clinical practice is to prescribe to 95% of the planning target volume (PTV) in 4D stereotactic body radiotherapy (SBRT) for lung. Frequently the PTV margin has a very low physical density so that the internal target volume (ITV) receives an unnecessarily high dose. This study investigates the alternative of prescribing to the ITV while including the effects of positional uncertainties. Five patients were retrospectively studied with volumetric modulated arc therapy treatment plans. Five plans were produced for each patient: a static plan prescribed to PTV D95% , three probabilistic plans prescribed to ITV D95% and a static plan re-prescribed to ITV D95% after inverse planning. For the three probabilistic plans, the scatter kernel in the dose calculation was convolved with a spatial uncertainty distribution consisting of either a uniform distribution extending ±5 mm in the three orthogonal directions, a distribution consisting of delta functions at ±5 mm, or a Gaussian distribution with standard deviation 5 mm. Median ITV D50% is 23% higher than the prescribed dose for static planning and only 10% higher than the prescribed dose for prescription to the ITV. The choice of uncertainty distribution has less than 2% effect on the median ITV dose. Re-prescribing a static plan and evaluating with a probabilistic dose calculation results in a median ITV D95% which is 1.5% higher than when planning probabilistically. This study shows that a robust probabilistic approach to planning SBRT lung treatments results in the ITV receiving a dose closer to the intended prescription. The exact form of the uncertainty distribution is not found to be critical.