Management of Patients with Cardiovascular Implantable Electronic Devices Undergoing Radiation Therapy: A National Survey of Canadian Multidisciplinary Radiation Oncology Professionals.

Purpose: This study aimed to characterize contemporary management of Canadian patients with cardiovascular implantable electronic devices (CIEDs) undergoing radiation therapy (RT) in light of updated American Association of Physicists in Medicine guidelines. Methods and Materials: A 22-question web-based survey was distributed to members of the Canadian Association of Radiation Oncology, Canadian Organization of Medical Physicists, and Canadian Association of Medical Radiation Technologists from January to February 2020. Respondent demographics, knowledge, and management practices were elicited. Statistical comparisons by respondent demographics were performed using χ2 and Fisher exact tests. Results: In total, 155 surveys were completed by 54 radiation oncologists, 26 medical physicists, and 75 radiation therapists in academic (51%) and community (49%) practices across all provinces. The majority of respondents (77%) had managed >10 patients with CIEDs in their career. Most respondents (70%) reported using risk-stratified institutional management protocols. Respondents used manufacturer recommendations, rather than American Association of Physicists in Medicine or institutionally recommended dose limits, when the manufacturer limit was 0 Gy (44%), 0 to 2 Gy (45%), or >2 Gy (34%). The majority of respondents (86%) reported institutional policies to refer to a cardiologist for CIED evaluation both before and after completion of RT. Cumulative dose to CIED, pacing dependence, and neutron production were considered during risk stratification by 86%, 74%, and 50% of participants, respectively. Dose and energy thresholds for high-risk management were not known by 45% and 52% of respondents, with radiation oncologists and radiation therapists significantly less likely to report thresholds than medical physicists (P < .001). Although 59% of respondents felt comfortable managing patients with CIEDs, community respondents were less likely to feel comfortable than academic respondents (P = .037). Conclusions: The management of Canadian patients with CIEDs undergoing RT is characterized by variability and uncertainty. National consensus guidelines may have a role in improving provider knowledge and confidence in caring for this growing population.

Cost Effectiveness Analysis of Radiofrequency Ablation (RFA) Versus Stereotactic Body Radiotherapy (SBRT) for Early Stage Renal Cell Carcinoma (RCC).

OBJECTIVES: To conduct a cost-effectiveness analysis of stereotactic body radiotherapy (SBRT) versus radiofrequency ablation (RFA) in the non-surgical management of early stage renal cell carcinoma (RCC) according to Consolidated Health Economic Evaluation Reporting Standards (CHEERS) criteria in the Canadian healthcare system. METHODS: A Markov state transition model was constructed for initial local treatment with RFA or SBRT for early stage, kidney confined, medically inoperable RCC in a hypothetical cohort. Incremental cost effectiveness ratios (ICER) were then calculated to compare the two treatments. The analysis was conducted over 5-year time horizon from the perspective of a publicly funded health system in Canada. Secondary analyses were conducted to assess the effect of small versus large size (< 4 cm vs. > 4 cm) RCC on ICERs. Multiple one-way deterministic sensitivity analysis were conducted. Discounting of 1.5% per year was applied. RESULTS: Over 5 years, SBRT economically dominated RFA with a gain of 4.103 quality-adjusted life years (QALYs) and a cost of $16,097, compared with 3.607 QALYs at a cost of $18,324 for RFA. The ICER was $4490 CAD less per QALY for SBRT in the base case analysis (BCE). In patients with small tumors (T1a), SBRT compared with RFA was more effective and marginally more costly, resulting in an ICER of $2207 CAD per QALY gained, while for larger tumors (T1b), SBRT was less costly and more effective than RFA, resulting in an ICER of -$22904. Sensitivity analysis demonstrated significant variability in the cost-effectiveness of SBRT versus RFA when parameters were varied, with rates of distant metastasis following RFA or SBRT having the greatest implications on ICERs. CONCLUSION: Overall, SBRT used as a primary treatment for RCC shows promising effectiveness at an overall reduction in cost compared with RFA in the Canadian healthcare system. The use of SBRT appears to be cost-effective for larger tumors as well as smaller tumors. The validity of these conclusions are highly sensitive to the accuracy of local and distant progression rates reported in previous studies, and may be adjusted as the available data on SBRT and RFA continues to evolve and mature.

The role of oophoropexy in patients with gynecological cancer who need radiation therapy.

Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.

A pilot study of stereotactic boost for malignant epidural spinal cord compression: clinical significance and initial dosimetric evaluation.

PURPOSE: Metastatic epidural spinal cord compression (MESCC) is a devastating complication of advanced malignancy, which can result in neurologic complications and significant deterioration in overall function and quality of life. Most patients are not candidates for optimal surgical decompression and as a result, receive urgent 3D conformal radiotherapy (3DCRT) to prevent or attempt to reverse neurologic progression. Multiple trials indicate that response and ambulatory rates after 3DCRT are inferior to surgery. The advent of stereotactic body radiation therapy (SBRT) has created a method with which a "radiosurgical decompression" boost may facilitate improve outcomes for MESCC patients. METHODS: We are conducting a pilot study to investigate SBRT boost after urgent 3D CRT for patients with MESCC. The aim of the study is to establish feasibility of this two-phase treatment regimen, and secondarily to characterize post-treatment ambulation status, motor response, pain control, quality of life and survival. DISCUSSION: We describe the study protocol and present a case report of one patient. A quality assurance review was conducted after the first seven patients, and resultant dose-constraints were revised to improve safety and feasibility of planning through more conservative organ at risk constraints. There have been no severe adverse events (grade 3-5) to date. We have illustrated clinical and dosimetric data of an example case, where a patient regained full strength and ambulatory capacity. CONCLUSIONS: Our study aims to determine if SBRT is a feasible option in addition to standard 3DCRT for MESCC patients, with the goal to consider future randomized trials if successful. Having a robust quality assurance process in this study ensures translatability going forward if future trials with multicenter and increased patient representation are to be considered. TRIAL REGISTRATION: clinicaltrials.gov; registration no. NCT03529708; https://clinicaltrials.gov/ct2/show/NCT03529708 ; First posted May 18, 2018.

Single versus multifraction radiotherapy for spinal cord compression: A systematic review and meta-analysis.

BACKGROUND: While multifraction radiotherapy (RT) regimens (MFRT) have been considered the standard of care in patients with metastatic epidural spinal cord compression (MESCC) with limited prognosis, recent randomized evidence has demonstrated that single fraction RT (SFRT) may be equivalent in terms of functional and overall outcomes. A systematic review and meta-analysis was conducted to determine the effects of SFRT compared to short course MFRT in patients with MESCC. METHODS: A search of OVID, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 2018 was conducted. Randomized and prospective non-randomized trials comparing SFRT and short course MFRT for MESCC were included. Data were analyzed using a random effects model, and relative risks (RR) or hazard ratios (HR) were reported with corresponding 95% confidence intervals (CI). Quality of evidence was assessed using the GRADE criteria. RESULTS: Overall 1717 articles were reviewed. Three randomized trials were eligible for inclusion (n = 712 patients). The pooled treatment effect for SFRT versus MFRT with respect to motor response was RR = 0.96 (95% CI = 0.86-1.07, I2 = 19%), HR = 1.00 (95% CI = 0.88-1.13, I2 = 0%) for OS, and RR = 0.97, (95% CI = 0.85-1.11, I2 = 61%) for bladder function. There was insufficient data to perform a meta-analysis on quality of life, toxicity or pain response, however available information suggests pain response appears similar between SFRT and MFRT. Overall quality of evidence was deemed moderate due to risk of bias. There was no evidence of an observed difference with respect to motor response, bladder dysfunction and OS between SFRT and MFRT for MESCC in patients with a limited prognosis.

Stereotactic body radiation therapy (SBRT) in the management of non-small-cell lung cancer: Clinical impact and patient perspectives.

Stereotactic body radiation therapy (SBRT) has emerged as a new technology in radiotherapy delivery, allowing for potentially curative treatment in many patients previously felt not to be candidates for radical surgical resection of stage I non-small-cell lung cancer (NSCLC). Several studies have demonstrated very high local control rates using SBRT, and more recent data have suggested overall survival may approach that of surgery in operable patients. However, SBRT is not without unique toxicities, and the balance of toxicity, and effect on patient-reported quality of life need to be considered with respect to oncologic outcomes. We therefore aim to review SBRT in the context of important patient-related factors, including quality of life in several domains (and in comparison to other therapies such as conventional radiation, surgery, or no treatment). We will also describe scenarios in which SBRT may be reasonably offered (i.e. elderly patients and those with severe COPD), and where it may need to be approached with some caution due to increased risks of toxicity (i.e. tumor location, patients with interstitial lung disease). In total, we hope to characterize the physical, emotional, and functional consequences of SBRT, in relation to other management strategies, in order to aid the clinician in deciding whether SBRT is the optimal treatment choice for each patient with early stage NSCLC.

The role of adjuvant therapy in stage IA serous and clear cell uterine cancer: A multi-institutional pooled analysis.

OBJECTIVE: As the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation. METHODS: Retrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models. RESULTS: Post-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74-88), 70% (62-78) and 90% (82-94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77-92), log-rank p=0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91-99) vs. 84% (76-89), log-rank p=0.007) and DFS (5-year 79% (66-88) vs. 71% (63-77), log-rank p=0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90-98) vs. 84% (77-89), log-rank p=0.014) and DFS (5-year 84% (74-91) vs. 69% (61-76), log-rank p=0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS. CONCLUSIONS: In stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging.

Radical chest wall resection and hyperfractionated accelerated radiotherapy for radiation-associated angiosarcoma of the breast: A safe and effective treatment strategy.

Radiation-associated angiosarcomas (RAS) of the breast are vascular tumors arising in a previous radiation field for primary breast cancer. They occur rarely but confer a high probability of local recurrence (LR) and poor prognosis. A wide range of treatment strategies exists due to limited evidence, and although resection is the definitive treatment, LR rates remain high. It has been suggested hyperfractionated accelerated radiotherapy (HART) has the potential to prevent LR. The sarcoma group at the Juravinski Cancer Centre (JCC) reports our experience of nine patients treated with radical resection and adjuvant HART. This is one of the largest reported cohorts we are aware of to receive this treatment. The JCC pathologic data base was reviewed between the year 2006-2015 for patients with RAS. Patients who received radical surgery and immediate HART were eligible. Patients underwent radical chest wall resection and en bloc mastectomy. Radiotherapy was then delivered to 4500 cGy in 45 fractions three times daily using parallel opposed photon beams and electron patching, or volumetric modulated arc therapy. Primary outcome was recurrence-free survival in months, and records were reviewed for descriptive reports of toxicity. We compared our results to other institutions experience with surgery alone or other adjuvant therapies. Median follow-up was 19 months (range 3-41 months). One of nine patients developed LR and developed metastasis, one died of other causes, and seven are alive with no recurrent disease. There were seven reports of mild skin toxicity during treatment. One patient developed chronic wound healing complications which eventually resolved and one patient developed asymptomatic radiation osteitis of a rib. On the basis of our experience at the JCC, we recommend treatment with radical chest wall resection and adjuvant HART to prevent recurrence in RAS patients. As demonstrated in our patients, the large normal tissue volume irradiated is tolerable with in combination with small fraction sizes, and no major toxicities were seen. Further investigation into adjuvant therapy regimens and prospective studies are required to reach consensus on optimal treatment for this disease.