Identification and separation of rigid image registration error sources, demonstrated for MRI-only image guided radiotherapy.

PURPOSE: Rigid image registration (RIR) accuracy is crucial for image guided radiotherapy (IGRT). However, existing clinical image registration assessment methods cannot separate and quantify RIR error sources. Herein, we develop an extension of the 'full circle method' for RIR consistency. Paired registration circuits are used to isolate sources of RIR error caused by reference dataset substitution, from those inherent to the underlying RIR. This approach was demonstrated in the context of MRI-only IGRT, assessing substitution of MRI-derived synthetic-CT (sCT) for conventional CT, in a cohort of rectal cancer patients. MATERIALS AND METHODS: Planning CT, MRI-derived sCT, and two CBCTs from seven rectal cancer patients were retrospectively registered with global and soft tissue clipbox based RIR. Paired registration circuits were constructed using two moving (cone beam CT) images and two reference images (CT and sCT), per patient. Differences between inconsistencies in registration circuits containing CT and sCT were used to determine changes in registration accuracy due to substitution of sCT for CT. RESULTS: sCT was found to be equivalent to CT under global RIR, with median differences of 0.05 mm and 0.01°. Soft tissue clipbox based RIR with sCT exhibited gross misregistration (>5 mm or 3°) for 3 patients. Registration consistency was degraded compared to CT across the cohort, with median differences of 0.54 mm and 0.15°. CONCLUSION: A paired registration circuit methodology for assessing RIR accuracy without ground truth information was developed and demonstrated for MRI-only IGRT in rectal cancer. This highlighted a reduction in clipbox based RIR consistency when sCT was substituted for conventional CT. The developed method enabled separation of degraded registration accuracy, from other error sources within the overall registration inconsistency. This novel methodology is applicable to any RIR scenario and enables analysis of the change in RIR performance on modification of image data or process.

Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma.

AIMS: To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. MATERIALS AND METHODS: One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. RESULTS: The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. CONCLUSIONS: Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

The Effect of Dose and Quality Assurance in Early Prostate Cancer Treated with Low Dose Rate Brachytherapy as Monotherapy.

AIMS: To examine the relationship between post-implant computed tomography dosimetry and long-term prostate-specific antigen relapse-free survival in patients treated with iodine 125 (I-125) low dose rate prostate brachytherapy as monotherapy and, second, to audit recent practice against Royal College of Radiologists' (RCR) guidelines after the re-introduction of post-implant dosimetry for all patients in our centre. MATERIALS AND METHODS: Between March 1995 and September 2007, 2157 consecutive patients with localised prostate cancer underwent I-125 permanent prostate brachytherapy as monotherapy in a single UK centre. All patients were transrectal ultrasound planned delivering a 145 Gy (TG 43) minimum peripheral dose. None received supplemental external beam radiotherapy. Post-implant computed tomography-based dosimetry was undertaken between 4 and 6 weeks after treatment and was available for 711 (33%). Outcomes were analysed in terms of the relationship of D90 to prostate-specific antigen relapse-free survival (nadir 2+ definition) and all patients had a minimum follow-up of 5 years. For contemporary patients from 2011, quality metrics from post-implant computed tomography as defined by RCR guidelines are presented. RESULTS: A mean D90 of 138.7 Gy (standard deviation 24.7) was achieved for the historic cohort. Biochemical control at 10 years was 76% in patients with D90 > 140 Gy and 68% in those with D90 < 140 Gy (P < 0.01). In current practice, over the last 3 years the mean (standard deviation) D90 has increased from 154 (15.3) Gy in 2011 to 164 (13.5) Gy in 2013. Similarly, an increase in the mean (standard deviation) V100 from 92 (4.4) to 95 (3.2) % is noted over time. No difference between clinicians was noted. CONCLUSION: D90 values of less than 140 Gy continue to be predictive of increased risk of recurrence of prostate cancer across risk groups with longer follow-up. Quality assurance can be used to ensure improved and consistent implant quality in a team with multiple clinicians.

Second primary cancers occurring after I-125 brachytherapy as monotherapy for early prostate cancer.

AIMS: Prostate brachytherapy may be associated with a lower risk of radiation-induced second primary cancer (SPC) as a significantly smaller volume of normal tissue is irradiated when compared with external beam techniques. Limited data are available as it has been a routine treatment option for less than 20 years. This study identified cases of SPC in patients who underwent I-125 prostate brachytherapy as monotherapy in a single institution. MATERIALS AND METHODS: SPC incidence was retrieved by conducting a UK cancer registry search (Northern and Yorkshire Cancer Registry and Information Service) for 1805 consecutive patients with localised prostate cancer who received monotherapy with I-125 brachytherapy from 1995 to 2006 at a single public hospital. Of 1730 UK residents, the completeness of the registry match was 91% (1574 patients). The mean age at treatment (interquartile range) of the cohort was 63 (58-68) years with 1100 patients (70%) over the age of 60 years at treatment. The median (range) follow-up was 8 (6-10) years with 487 patients (31%) having 10 years or more. RESULTS: In total, 170 patients (10.8%) were diagnosed with second primaries (1 year or more after implant); 20 of these were bladder and 10 rectal cancers. The 10 year cumulative incidences were 14.6, 1 and 0.84% for any second malignancy, bladder and rectal cancer, respectively. Only the standardised incidence rate (SIR) for bladder cancer was higher at 1.54 (95% confidence interval 0.96-2.46) compared with the general population. The SIR for bladder cancer was higher in the first few years after treatment, suggesting that the increased incidence of bladder cancer is due to increased urological surveillance. CONCLUSIONS: Overall, the incidence of SPC after I-125 is comparable with other published data with no significant excess more than 5 years from treatment. Mortality secondary to SPC of the bladder or rectum is unusual.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PURPOSE: In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. METHODS: A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. RESULTS: In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). CONCLUSIONS: ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

Recto-urethral fistula following brachytherapy for localized prostate cancer.

OBJECTIVE: The use of prostate brachytherapy (BT) in the management of prostate cancer is increasing. BT is often chosen because of its perceived lower toxicity when compared with other radical therapy options. Rarely however serious complications can occur. One such complication is recto-urethral fistula (RUF). We report the incidence of RUF following BT at our centre and review the potential factors in fistula development. METHOD: A prospectively collected database was used to identify cases of RUF among 1455 patients treated with prostate BT at a single UK centre with at least 2 years of follow up. This included patients treated with BT monotherapy, as well as those treated with BT combined with external beam radiotherapy and BT used as salvage as all these groups have a higher incidence of RUF. Implant dose and volume characteristics for those patients, their co-morbidities and history of endoscopic procedures were recorded. RESULTS: Recto-urethral fistula was identified in three (0.2%) patients, occurring at 19-27 months following BT. All these patients had BT monotherapy. All three patients had rectal symptoms after their BT and had been investigated with endoscopy and low rectal biopsy. Subsequent surgical management with faecal and/or urinary diversion was required. On review of patients' BT details, radiation dose and volume parameters were higher on the postprocedure CT calculations than had been suggested by the preimplant plan. No other predisposing risk factors for RUF were identified. CONCLUSION: The incidence of RUF in our population is low. RUF following BT has been associated with rectal biopsy in previous series and this is confirmed in our report. Gastrointestinal specialists should not perform biopsy of the anterior rectum in patients who have had BT unless there is a very high clinical suspicion of malignancy.