Management of stage I testicular cancer.

PURPOSE OF REVIEW: Testicular cancer is the most common solid malignancy amongst young men, and a large proportion present with stage I disease. The options for management following radical orchiectomy are multifold. We review here approaches to treatment in this setting, providing an update on recent publications. RECENT FINDINGS: At Princess Margaret Cancer Centre, we maintain a nonrisk adapted active surveillance approach. With a dedicated surveillance program using low-dose computed tomography imaging, patients are appropriately identified early for treatment on relapse. There are ongoing investigations into minimizing toxicities of treatments for relapse, and in particular, retroperitoneal lymph node dissection (RPLND) presents an attractive alternative. This, though, remains investigational in the setting of seminoma. SUMMARY: Testicular cancer is a highly curable malignancy. In stage I disease, an active surveillance approach following radical orchiectomy is preferred, irrespective of risk-profile. This approach serves to limit the toxicity of adjuvant treatment in a significant proportion of patients, while maintaining excellent survival outcomes.

Repeatability and reproducibility of prostate apparent diffusion coefficient values on a 1.5 T magnetic resonance linear accelerator.

Background and Purpose: Integrated magnetic resonance linear accelerator (MR-Linac) systems offer potential for biologically based adaptive radiation therapy using apparent diffusion coefficient (ADC). Accurate tracking of longitudinal ADC changes is key to establishing ADC-driven dose adaptation. Here, we report repeatability and reproducibility of intraprostatic ADC using deformable image registration (DIR) to correct for inter-fraction prostate changes. Materials and Methods: The study included within-fraction repeat ADC measurements for three consecutive fractions for 20 patients with prostate cancer treated on a 1.5 T MR-Linac. We deformably registered successive fraction T2-weighted images and applied the deformation vector field to corresponding ADC maps to align to fraction 2. We delineated gross tumour volume (GTV), peripheral zone (PZ) and prostate clinical target volume (CTV) regions-of-interest (ROIs) on T2-weighted MRI and copied to ADC maps. We computed intraclass correlation coefficients (ICC) and percent repeatability coefficient (%RC) to determine within-fraction repeatability and between-fraction reproducibility for individual voxels, mean and 10th percentile ADC values per ROI. Results: The ICC between repeats and fractions was excellent for mean and 10th percentile ADC in all ROIs (ICC > 0.86), and moderate repeatability and reproducibility existed for individual voxels (ICC > 0.542). Similarly, low %RC within-fraction (4.2-17.9 %) mean and 10th percentile ADC existed, with greater %RC between fractions (10.2-36.8 %). Higher %RC existed for individual voxel within-fraction (21.7-30.6 %) and between-fraction (32.1-34.5 %) ADC. Conclusions: Results suggest excellent ADC repeatability and reproducibility in clinically relevant ROIs using DIR to correct between-fraction anatomical changes. We established the precision of voxel-level ADC tracking for future biologically based adaptation implementation.

Utilizing clinical, pathological and radiological information to guide postoperative radiotherapy in prostate cancer.

INTRODUCTION: A detectable and rising PSA following radical prostatectomy is indicative of recurrent prostate cancer. Salvage radiotherapy (SRT) with/without androgen deprivation therapy represents the main treatment option for these patients and has been historically associated with a biochemical control rate of ~70%. To determine the optimal timing, diagnostic workup, radiotherapy dosefractionation, treatment volume, and use of systemic therapy, several informative studies have been conducted in the last decade. AREAS COVERED: This review examines the recent evidence to guide radiotherapy decision making in the SRT setting. Key topics include adjuvant vs salvage RT, utilization of molecular imaging and genomic classifiers, length of androgen deprivation therapy, inclusion of elective pelvic volume, and emerging role for hypofractionation. EXPERT OPINION: Recently reported trials, conducted in an era prior to the routine use of molecular imaging and genomic classifiers, have been pivotal in establishing the current standard of care for SRT in prostate cancer. However, decisions about radiation treatment and systemic therapy may be tailored based on available prognostic and predictive biomarkers. Data from contemporary clinical trials are awaited to define and establish individualized, biomarker-driven approaches for SRT.

Practice-based training strategy for therapist-driven prostate MR-Linac adaptive radiotherapy.

Purpose: To develop a practice-based training strategy to transition from radiation oncologist to therapist-driven prostate MR-Linac adaptive radiotherapy. Methods and materials: In phase 1, 7 therapists independently contoured the prostate and organs-at-risk on T2-weighted MR images from 11 previously treated MR-Linac prostate patients. Contours were evaluated quantitatively (i.e. Dice similarity coefficient [DSC] calculated against oncologist generated online contours) and qualitatively (i.e. oncologist using a 5-point Likert scale; a score ≥ 4 was deemed a pass, a 90% pass rate was required to proceed to the next phase). Phase 2 consisted of supervised online workflow with therapists required no intervention from the oncologist on 10 total cases to advance. Phase 3 involved unsupervised therapist-driven workflow, with offline support from oncologists prior to the next fraction. Results: In phase 1, the mean DSC was 0.92 (range 0.85-0.97), and mean Likert score was 3.7 for the prostate. Five therapists did not attain a pass rate (3-5 cases with prostate contour score < 4), underwent follow-up one-on-one review, and performed contours on a further training set (n = 5). Each participant completed a median of 12 (range 10-13) cases in phase 2; of 82 cases, minor direction were required from the oncologist on 5 regarding target contouring. Radiation oncologists reviewed 179 treatment fractions in phase 3, and deemed 5 cases acceptable but with suggestions for next fraction; all other cases were accepted without suggestions. Conclusion: A training stepwise program was developed and successfully implemented to enable a therapist-driven workflow for online prostate MR-Linac adaptive radiotherapy.

Case Report: MR-Guided Adaptive Radiotherapy, Some Room to Maneuver.

Background: A magnetic resonance linear accelerator (MR-Linac) provides superior soft tissue contrast to evaluate inter- and intra-fraction motion and facilitate online adaptive radiation therapy (ART). We present here an unusual case of locally advanced castrate-resistant prostate cancer treated with high-dose palliative ultra-hypofractionated radiation therapy on the MR-Linac with significant inter-fraction tumor regression. Case Presentation: The patient was a 65-year-old man diagnosed with metastatic prostate cancer to bone and pelvic lymph nodes 7 years prior. At diagnosis, he presented with a PSA of 23 ng/ml and was commenced on a luteinizing hormone-releasing hormone agonist, achieving a PSA nadir of 4.68 ng/ml at 12 months. The patient subsequently had progressive lower urinary tract symptoms, his PSA increased to 47 ng/ml, and there was a markedly enlarged pelvic mass involving the prostate with gross extra-capsular disease and invasion into the posterior bladder wall. The patient was referred for palliative radiation to the pelvic mass due to urinary symptoms, pain, and lower limb paraesthesia. Treatment was planned to be delivered on the MR-Linac with a schedule of 36 Gy over 6 weekly factions allowing for maximal target dose delivery while minimizing surrounding organs at risk (OARs) radiation exposure. Unexpectedly, the target volume had a marked 49% (453 cc to 233 cc) reduction that was accounted for in the online adaptive process. A new reference plan was generated after 3 fractions to add sacral plexus as an OAR, previously not visible due to mass encroachment. The patient reported ongoing reduction in urinary symptoms, pelvic pain, and lower limb paresthesia by the end of treatment. Conclusion: Using daily MR-guided ART, improved visualization of the changing target and OARs ensured safe dose escalation. The unexpected positive response of the target and improved patient outcomes demonstrated the added value of the MR-Linac for online adaptive radiotherapy in this setting.

Impact of intrafraction changes in delivered dose of the day for prostate cancer patients treated with stereotactic body radiotherapy via MR-Linac.

Purpose: The purpose of this study is to evaluate the impact of intrafraction pelvic motion by comparing the adapted plan dose (APD) and the computed delivered dose of the day (DDOTD) for patients with prostate cancer (PCa) treated with SBRT on the MR-Linac. Methods: Twenty patients with PCa treated with MR-guided adaptive SBRT were included. A 9-field IMRT distribution was adapted based on the anatomy of the day to deliver a total prescription dose of 3000 cGy in 5 fractions to the prostate plus a 5 mm isotropic margin. Prostate, bladder, and rectum were re-contoured on the MR-image acquired during treatment delivery (MRBO). DDOTD was computed by propagating the dose from the daily adapted plan generated during treatment onto the MRBO. Results: Target coverage was met for all fractions, however, computed DDOTD was significantly less than the APD (p < 0.05). During an average treatment of 53 min, mean bladder volume increased by 116%, which led to a significant decrease in the DDOTD bladder D40% (p < 0.001). However, DDOTD to bladder 5 cc was significantly higher (p < 0.001) than APD. Rectum intrafraction changes were observed based on a volume change of -20% to 83% and presence of significant dose changes from APD to DDOTD for rectum D20% (p < 0.05) and D1cc (p < 0.0001). Conclusions: Intrafraction motion observed during prostate SBRT treatment on the MR-Linac have dosimetric impacts on both the target and organs at risk. Post-treatment computation using DDOTD may inform adaptation beyond anatomic changes in subsequent treatment fractions to best capitalize on MR-Linac technology and widen the therapeutic index of SBRT for PCa.

Dosimetric comparison of MR-guided adaptive IMRT versus 3DOF-VMAT for prostate stereotactic radiotherapy.

INTRODUCTION: To compare the dosimetry of prostate stereotactic radiotherapy (SBRT) delivered by adaptive intensity modulated radiotherapy (A-IMRT) and 3 degree of freedom volumetric modulated arc therapy (3DOF-VMAT). METHODS & MATERIALS: Twenty-five prostate patients treated with High Dose Rate (HDR) brachytherapy followed by SBRT were included (fifteen with hydrogel spacer in place for treatment). Interfraction changes in the volume of prostate, rectum and bladder were measured. Fractional dose to these structures was estimated for A-IMRT and 3DOF-VMAT for comparison against the corresponding reference dose and between each other. RESULTS: Clinically acceptable dose was delivered to prostate in all 125 fractions through A-IMRT and 3DOF-VMAT. A-IMRT was better than 3DOF-VMAT in reducing dose to 1 cm3 of rectum. Conversely, 3DOF-VMAT was superior in sparing 50% and 20% of rectum. When comparing the reference and delivered dose, there was no significant difference for Bladder D5cm3 for either technique. However, rectum in the high dose region benefited more from A-IMRT by being irradiated to a lower than reference dose in more fractions than 3DOF-VMAT. Hydrogel spacer reduced the rectal dose and was associated with a smaller deviation from reference dose for rectum D50% for A-IMRT. CONCLUSIONS: Despite the presence of large interfraction organ volumes changes, clinically acceptable dose was delivered to the prostate by both systems. A-IMRT facilitated a greater rectal sparing from the high dose region than 3DOF-VMAT. Further reduction in rectal dose could be achieved by hydrogel spacer to displace the rectum, or by adaptation delivered by VMAT.

Current Evidence for Stereotactic Body Radiotherapy in Lung Metastases.

Lung metastases are the second most common malignant neoplasms of the lung. It is estimated that 20-54% of cancer patients have lung metastases at some point during their disease course, and at least 50% of cancer-related deaths occur at this stage. Lung metastases are widely accepted to be oligometastatic when five lesions or less occur separately in up to three organs. Stereotactic body radiation therapy (SBRT) is a noninvasive, safe, and effective treatment for metastatic lung disease in carefully selected patients. There is no current consensus on the ideal dose and fractionation for SBRT in lung metastases, and it is the subject of study in ongoing clinical trials, which examines different locations in the lung (central and peripheral). This review discusses current indications, fractionations, challenges, and technical requirements for lung SBRT.

National survey on image-guided radiotherapy practice in New Zealand.

INTRODUCTION: This survey aimed to assess the use of image-guided radiotherapy (IGRT) within New Zealand (NZ) and evaluate the quality of IGRT delivery. METHOD: All nine centres in NZ were invited to participate in an online survey in November 2015. Questions were asked on type of IGRT technologies available, IGRT use by tumour site and frequency of imaging. In addition, questions were asked in reference to the American Society for Radiation Oncology (ASTRO) White Paper recommendations on safe practice of IGRT. RESULTS: Seven of the nine centres (78%) responded. Kilovoltage cone-beam CT (CBCT), kilovoltage planar imaging and megavoltage electronic portal imaging were the most commonly used IGRT technologies. CBCT was most frequently used in gynaecology (100%), genitourinary (86%) and head and neck (86%) sites. Despite the availability of similar IGRT technologies, there was significant variation in their application between centres. All centres used online IGRT; however, the frequency of imaging varied across the tumour sites and individual centres. Daily online IGRT use ranged from 43% to 86% across the tumour sites. Overall, there was good compliance by the NZ centres to the White Paper recommendations, with at least 71% reached for each element. However, the compliance rates for the individual centres ranged between 50% and 100%. The most commonly identified barrier to IGRT use was lack of guidelines/education (43%). CONCLUSION: Image-guided radiotherapy is widely used in NZ; however, there is a wide variation in its application between centres. Detailed tumour site-specific, imaging modality-specific national guidelines will allow standardization of IGRT practices.