Estimated dose to site of loco-regional recurrence after radiotherapy in anal cancer using point of origin methods.

Background and purpose: Loco-regional recurrence (LRR) dominates the failure pattern after curative radiotherapy in anal cancer. The aim of this study was to estimate dose of LRRs in anal cancer using a point of origin-based method. Method and materials: Of 321 patients with squamous cell carcinoma of the anus, 31 patients with LRR (29 local recurrences and 5 regional lymph node recurrences) were available for analysis. The recurrence volumes were delineated on recurrence magnetic resonance imaging (rMRI). Rigid and subsequent deformable co-registration of planning computerised tomography scans and rMRI were performed. Point of origin was estimated as the centre of mass (COM) and an observer-based point of origin (obs-PO). Doses to COM and obs-PO, as well as the full recurrence volume, were estimated and the relation to target volumes was extracted. Results: The median minimum dose to COM was 63.8 Gy (range 32.5-65.1 Gy) and 63.7 Gy (range 35.5-65.2 Gy) to obs-PO of local recurrences. COM was included in the high dose volume (64 Gy) in 86 % of cases, and obs-PO was included in 75 % of cases. There was no difference in minimum dose to COM and obs-PO, and the median distance between the two points was 3.3 mm (range 0.6-19.8 mm). No recurrences occurred in primarily boosted lymph nodes. Conclusion: The majority of LLRs were located within the high dose volume indicating radioresistance as the primary cause of recurrence in anal cancer. No difference between the use of COM and obs-PO was evident.

Toward 3D dose verification of an electronic brachytherapy source with a plastic scintillation detector.

BACKGROUND: Electronic brachytherapy (eBT) is considered a safe treatment with good outcomes. However, eBT lacks standardized and independent dose verification, which could impede future use. PURPOSE: To validate the 3D dose-to-water distribution of an electronic brachytherapy (eBT) source using a small-volume plastic scintillation detector (PSD). METHODS: The relative dose distribution of a Papillon 50 (P50) (Ariane Medical Systems, UK) eBT source was measured in water with a PSD consisting of a cylindrical scintillating BCF-12 fiber (length: 0.5 mm, Ø: 1 mm) coupled to a photodetector via an optical fiber. The measurements were performed with the PSD mounted on a motorized stage in a water phantom (MP3) (PTW, Germany). This allowed the sensitive volume of the PSD to be moved to predetermined positions relative to the P50 applicator, which pointed vertically downward while just breaching the water surface. The percentage depth-dose (PDD) was measured from 0 to 50 mm source-to-detector distance (SDD) in 1-3 mm steps. Dose profiles were measured along two perpendicular axes at five different SDDs with step sizes down to 0.5 mm. Characterization of the PSD consisted of determining the energy correction through Monte Carlo (MC) simulation and by measuring the stability and dose rate linearity using a well-type ionization chamber as a reference. The measured PDD and profiles were validated with corresponding MC simulations. RESULTS: The measured and simulated PDD curves agreed within 2% (except at 0 mm and 43 mm depth) after the PSD measurements were corrected for energy dependency. The absorbed dose decreased by a factor of 2 at 7 mm depth and by a factor of 10 at 26 mm depth. The measured dose profiles showed dose gradients at the profile edges of more than 50%/mm at 5 mm depth and 15%/mm at 50 mm depth. The measured profile widths increased 0.66 mm per 1 mm depth, while the simulated profile widths increased 0.74 mm per 1 mm depth. An azimuthal dependency of > 10% was observed in the dose at 10 mm distance from the beam center. The total uncertainty of the measured relative dose is < 2.5% with a positional uncertainty of 0.4 mm. The measurements for a full 3D dose characterization (PDD and profiles) can be carried out within 8 h, the limiting factor being cooling of the P50. CONCLUSION: The PSD and MP3 water phantoms provided a method to independently verify the relative 3D dose distribution in water of an eBT source.

Density calibrated cone beam CT as a tool for adaptive radiotherapy.

BACKGROUND: Visual inspections of anatomical changes observed on daily cone-beam CT (CBCT) images are often used as triggers for radiotherapy plan adaptation to avoid unacceptable dose levels to the target or OARs. Direct CBCT dose calculations would improve the ability to adapt only those plans where dosimetric changes are observed. This study investigates the accuracy of dose calculations on CBCTs. MATERIALS AND METHODS: Calibration curves were obtained for CBCT imagers at nine identical accelerators. CBCT scans of a phantom with different density inserts were recorded for two scan modes (Head-Neck and Pelvis) and mean calibration curves were calculated. Subsequently, CBCT scans of the phantom with six different density inserts were recorded, the dose distributions on the CBCTs were calculated and compared to dose on the planning CT (pCT). The uncertainty was quantified by the dosimetric difference between the pCT and the CBCT. The two mean calibration curves were used to calculate the daily delivered CBCT dose for ten Head-Neck-, eleven Lung-, and ten pelvic patients. Additional patient calculations were performed using low-HU empirically corrected calibration curves. Patient doses were compared on target coverage and mean dose, and D1cc for OARs. RESULTS: The dose differences between pCT and CBCT for phantom data were small for all DVH parameters, with mean deviations below ±0.6% for both CBCT modes. For patient data, it was found that low-HU corrected calibration curves performed the best. The mean deviations for the mean dose and coverage of the target were 0.2%±0.7% and 0.1%±0.6%, across all patient groups. CONCLUSION: Dose calculation on CBCT images results in target coverage and mean dose with an accuracy of the order of 1%, which makes this acceptable for clinical use. The CBCT mode specific calibration curves can be used at all identical imaging devices and for all patient groups.

Robustness of elective lymph node target coverage with shrinking Planning Target Volume margins in external beam radiotherapy of locally advanced cervical cancer.

BACKGROUND AND PURPOSE: Image-Guidance decreases set-up uncertainties, which may allow for Planning Target Volume (PTV) margins reduction. This study evaluates the robustness of the elective lymph node target coverage to translational and rotational set-up errors in combination with shrinking PTV margins and determines the gain for the Organs At Risk (OARs). MATERIAL AND METHODS: Ten cervix cancer patients who underwent external beam radiotherapy with 45 Gy/25Fx were analysed. Daily Image-Guidance was based on bony registration of Cone Beam CT (CBCT) to planning CT (pCT) and daily couch correction (translation and yaw). On each pCT, four Volumetric Modulated Arc Therapy dose-plans were generated with PTV margins of 0, 3, 5 and 8 mm. The elective clinical target volume (CTV-E) was propagated from daily CBCTs to the pCT to evaluate daily CTV-E dose. Additional systematic translational isocenter shifts of 2 mm were simulated. D98% (dose received by 98% of the volume of interest) and D99.9% were extracted from each CTV-E for all dose-plans and scenarios. Total dose was accumulated by Dose-Volume Histogram addition. The dosimetric impact of PTV margin reduction on the OARs was evaluated through V30Gy (volume included within the 30 Gy isodose), V40Gy and body V43Gy. RESULTS: When decreasing the PTV margin from 5 to 0 mm, bowel V30Gy was decreased by 13% (from 247 cm3 to 214 cm3), body V43Gy by 19% (from 1462 cm3 to 1188 cm3) and PTV by 39% (from 1416 to 870 cm3). The dosimetric impact of combined systematic shifts and residual rotations on the elective target with a 0 mm PTV margin was a decrease of D98% (mean ±â€¯SD) from 44.1 Gy ±â€¯0.4 Gy to 43.7 Gy ±â€¯0.8 Gy and a minimum of 42.4 Gy. CONCLUSION: PTV margin reduction from 5 to 0 mm induced significant OARs dosimetric gains while elective target coverage remained robust to positioning uncertainties.

Cone beam computed tomography-based monitoring and management of target and organ motion during external beam radiotherapy in cervical cancer.

BACKGROUND AND PURPOSE: Organ motion is a challenge during high-precision external beam radiotherapy in cervical cancer, and improved strategies for treatment adaptation and monitoring of target dose coverage are needed. This study evaluates a cone beam computed tomography (CBCT)-based approach. MATERIALS AND METHODS: In twenty-three patients, individualized internal target volumes (ITVs) were generated from pre-treatment MRI and CT scans with full and empty bladders. The target volumes encompassed high-risk clinical target volume (CTV-T HR) (gross tumor volume + remaining cervix) and low risk (LR) CTV-T (CTV-T HR + uterus + parametriae + upper vagina). Volumetric Modulated Arc Therapy (VMAT) was used to deliver a dose of 45 Gy in 25 fractions. CBCTs were used for setup and for radiation therapists (RTTs) to evaluate the target coverage (inside/outside the planning target volume). CBCTs were reviewed offline. Estimates of the dose delivered with minimum (point) doses across all fractions to CTV-T HR (aim 42.75 Gy) and CTV-T LR (aim 40 Gy) were assessed. In patients with insufficient dose coverage, re-plans were generated based on previous imaging. RESULTS: Median (range) of the ITV-margins (mean of anterior-posterior margins) related to uterus and cervix was 1.2 (0.5-2.2 and 1.0-2.1) cm. RTTs were able to assess the target coverage in 90% of all CBCTs (505/563). With re-planning, one patient had considerable benefit (12.7 Gy increase of minimum dose) to CTV-T LR_vagina, four patients had improved dose to the CTV-T LR_uterus (1.2-1.8 Gy), and 3 patients did not benefit from re-planning. CONCLUSIONS: Daily CBCT-based monitoring of target coverage by the RTTs has proven safe with limited workload. It allows for reduction in the treated volumes without compromising the target dose coverage.

Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer - A multicentre dose planning study.

BACKGROUND AND PURPOSE: Organ preservation strategies are increasingly being explored for early rectal cancer. This requires revision of target volumes according to disease stage, as well as new guidelines for treatment planning. We conducted an international, multicentre dose planning study to develop robust planning objectives for modern radiotherapy of a novel mesorectal-only target volume, as implemented in the STAR-TReC trial (NCT02945566). MATERIALS AND METHODS: The published literature was used to establish relevant dose levels for organ at risk (OAR) plan optimisation. Ten representative patients with early rectal cancer were identified. Treatment scans had mesorectal target volumes as well as bowel cavity, bladder and femoral heads outlined, and were circulated amongst the three participating institutions. Each institution produced plans for short course (SCRT, 5 × 5 Gy) and long course (LCRT, 25 × 2 Gy) treatment, using volumetric modulated arc therapy on different dose planning systems. Optimisation objectives for OARs were established by determining dose metric objectives achievable for ≥90% of plans. RESULTS: Sixty plans, all fulfilling target coverage criteria, were produced. The planning results and literature review suggested optimisation objectives for SCRT: V 10Gy < 180 cm3, V 18Gy < 110 cm3, V 23Gy < 85 cm3 for bowel cavity; V 21Gy < 15% and V 25Gy < 5% for bladder; and V 12.5Gy < 11% for femoral heads. Corresponding objectives for LCRT: V 20Gy < 180 cm3, V 30Gy < 130 cm3, V 45Gy < 90 cm3 for bowel cavity; V 35Gy < 22% and V 50Gy < 7% for bladder; and V 25Gy < 15% for femoral heads. Constraints were validated across all three institutions. CONCLUSION: We utilized a multicentre planning study approach to develop robust planning objectives for mesorectal radiotherapy for early rectal cancer.

Prospective evaluation of acute toxicity and patient reported outcomes in anal cancer and plan optimization.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) is the standard therapy for localized anal cancer (AC), but this treatment is associated with substantial toxicity. However, there is a lack of prospectively collected toxicity and patient reported outcome (PRO) data from larger cohorts. The purpose was to prospectively collect and determine agreement between physician assessed toxicity (CTCAE) and PRO during and after CRT and to compare IMRT, VMAT and proton-based planning in a subgroup of patients. MATERIAL AND METHODS: Patients, treated with CRT for AC, were included between 2015 and 2017. NCI-CTCAE v.4.0, EORTC QLQ-C30 and CR29 data were collected baseline, mid-therapy, end-of therapy and 2-4 weeks posttherapy. Treatment planning with 5- or 6-fixed field IMRT, 2 and 3 arc VMAT, and 3- and 4-field proton plans were compared. RESULTS: One-hundred patients were included. Both CTCAE and PROs related to acute toxicity reached a maximum at end of therapy. Incidences of PROs were markedly higher with only slight to fair agreement to CTCAE, (κ 13-37). Comparative planning revealed dosimetric equality of IMRT and VMAT plans, but superiority of proton plans. CONCLUSIONS: The high incidence of PRO scores and weak agreement to CTCAE suggest that PROs are important tools complementary to CTCAE in evaluating patient symptoms during and after CRT. Proton therapy has the potential to lower radiation doses to most organs at risk.

Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study.

INTRODUCTION: Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery. METHODS AND ANALYSIS: STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2. ETHICS AND DISSEMINATION: The medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14240288, 20 October 2016. NCT02945566; Pre-results, October 2016.