Stereotactic Ablative Radiotherapy for Gynecological Oligometastatic and Oligoprogessive Tumors.

Importance: The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake. Objective: To evaluate the outcomes of SABR in patients with oligometastatic and oligoprogressive gynecologic cancers. Design, Setting, and Participants: In this retrospective pooled analysis, patients with oligometastatic and oligoprogressive gynecologic cancers receiving SABR at 5 institutions from Canada and the US were studied. Data were collected from January 2011 to December 2020, and data were analyzed from January to December 2023. Exposure: Stereotactic ablative radiotherapy. Main Outcomes and Measures: Cumulative incidence of local and distant recurrence, chemotherapy-free survival (CFS), and overall survival (OS) probabilities after SABR were calculated using Kaplan-Meier methods. Univariable and multivariable analysis was conducted using Cox regression methods. Results: A total of 215 patients with 320 lesions meeting criteria were included in the analysis; the median (range) age at primary diagnosis was 59 (23-86) years. The median (range) follow-up from SABR was 18.5 (0.1-124.5) months. The primary site included the endometrium (n = 107), ovary (n = 64), cervix (n = 30), and vulva or vagina (n = 14). Local cumulative incidence of recurrence was 13.7% (95% CI, 9.4-18.9) and 18.5% (95% CI, 13.2-24.5) at 1 and 5 years, respectively. Distant cumulative incidence of recurrence was 48.5% (95% CI, 41.4-55.1) and 73.1% (95% CI, 66.0-79.0) at 1 and 5 years, respectively. OS was 75.7% (95% CI, 69.2-81.1) and 33.1% (95% CI, 25.3-41.1) at 1 and 5 years, respectively. The median CFS was 21.7 months (95% CI, 15.4-29.9). On multivariable analysis, local recurrence was significantly associated with nodal metastasis, lesion size, biologically effective dose, treatment indication, institution, and primary disease type. Distant progression-free survival was associated with nodal targets and lesion size. OS and CFS were significantly associated with lesion size. Conclusions and Relevance: In this study, SABR appeared to have excellent local control with minimal toxic effects in this large patient group, and certain patients may achieve durable distant control and OS as well. It may be possible to delay time to chemotherapy in select patient subtypes and therefore reduce associated toxic effects. Prospective multicenter trials will be critical to establish which characteristics procure the greatest benefit from SABR use and to define the ideal time to implement SABR with other oncologic treatments.

The Effectiveness and Safety of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Oligoprogressive Breast Cancer: A Systematic Review.

Stereotactic body radiotherapy (SBRT) has emerged as a technique to treat oligoprogressive sites among patients with breast cancer who are otherwise doing well on systemic therapy. This study systematically reviewed the efficacy and safety of SBRT in the setting of oligoprogressive breast cancer. A literature search was conducted in the MEDLINE database. Studies regarding SBRT and oligoprogressive breast cancer were included. Key outcomes of interest were toxicity, local control, progression, and overall survival. From 863 references, five retrospective single-center cohort studies were identified. All studies included patients with both oligometastatic and oligoprogressive disease; 112 patients with oligoprogressive breast cancer were identified across these studies. Patient age ranged from 22 to 84, with a median of 55 years of age. Most patients had hormone-receptor-positive and HER2-negative disease. SBRT doses varied from 24 to 60 Gy in 1-10 fractions based on the location/size of the lesion. Forty toxicity events were reported, of which the majority (n = 25, 62.5%) were grade 1-2 events. Among 15 patients who received SBRT concurrently with a CDK4/6 inhibitor, 37.5% of patients experienced grade 3-5 toxicities. Progression-free and overall survival ranged from 17 to 57% and 62 to 91%, respectively. There are limited data on the role of SBRT in oligoprogressive breast cancer, and prospective evaluation of this strategy is awaited to inform its safety and efficacy.

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.

Mepitel Film for the Prevention of Acute Radiation Dermatitis in Breast Cancer: A Randomized Multicenter Open-Label Phase III Trial.

PURPOSE: Radiation dermatitis (RD) is common in patients undergoing breast radiotherapy. Mepitel film (MF) can reduce RD, but the results from two randomized controlled trials are conflicting. We aimed to conduct a confirmatory randomized controlled trial in patients at risk of RD. METHODS: Patients were randomly assigned to receive MF or standard care (2:1 ratio). Patients with large breasts after lumpectomy (bra size ≥ 36 inches or cup size ≥ C) or after mastectomy were eligible. Stratification factors included surgery type, dose fractionation, and administration of boost/bolus. The primary end point was grade (G) 2 or 3 RD using the Common Terminology Criteria for Adverse Events v5.0. Secondary end points included patient- and clinician-reported outcomes. RESULTS: Between January 2020 and May 2022, 376 patients were included in the modified intention-to-treat analysis. The incidence of G2 or 3 RD was significantly lower in MF patients compared with standard care (n = 39/251, 15.5%; 95% CI, 11.3 to 20.6% v n = 57/125, 45.6%; 95% CI, 36.7 to 54.8% respectively, odds ratio (OR): 0.20, P < .0001). Benefits of MF remained significant in patients who developed G 3 RD (n = 7, 2.8%; 95% CI, 1.1 to 5.7% v n = 17, 13.6%; 95% CI, 8.1 to 20.9%, OR: 0.19) and moist desquamation (n = 20, 8.0%; 95% CI, 4.9 to 12.0% v n = 24, 19.2%; 95% CI, 12.7 to 27.1%, OR: 0.36). When evaluating the combined patient and health care provider score using Radiation-Induced Skin Reaction Assessment Scale, the MF arm had significantly lower scores (P < .0001). Individual items on the Radiation-Induced Skin Reaction Assessment Scale also favored the MF for both patient- and clinician-reported outcomes. Blistering/peeling, erythema, pigmentation, and edema were significantly reduced in the MF arm. Three patients removed the film prematurely because of rash (n = 2) and excessive pruritus (n = 1). CONCLUSION: MF significantly reduces RD in patients undergoing breast radiotherapy.

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.

Quality-of-Life Outcomes and Toxic Effects Among Patients With Cancers of the Uterus Treated With Stereotactic Pelvic Adjuvant Radiation Therapy: The SPARTACUS Phase 1/2 Nonrandomized Controlled Trial.

Importance: Adjuvant radiation plays an important role in reducing locoregional recurrence in patients with uterine cancer. Although hypofractionated radiotherapy may benefit health care systems and the global community while decreasing treatment burden for patients traveling for daily radiotherapy, it has not been studied prospectively nor in randomized trials for treatment of uterine cancers, and the associated toxic effects and patient quality of life are unknown. Objective: To evaluate acute genitourinary and bowel toxic effects and patient-reported outcomes following stereotactic hypofractionated adjuvant radiation to the pelvis for treatment of uterine cancer. Design, Setting, and Participants: The Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS) phase 1/2 nonrandomized controlled trial of patients accrued between May 2019 and August 2021 was conducted as a multicenter trial at 2 cancer centers in Ontario, Canada. In total, 61 patients with uterine cancer stages I through III after surgery entered the study. Interventions: Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly. Main Outcomes and Measures: Assessments of toxic effects and patient-reported quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and endometrial EN24) were collected at baseline, fractions 3 and 5, and at 6 weeks and 3 months of follow-up. Descriptive analysis was conducted, calculating means, SDs, medians, IQRs, and ranges for continuous variables and proportions for categorical variables. Univariate generalized linear mixed models were generated for repeated measurements on the quality-of-life scales. Results: A total of 61 patients were enrolled (median age, 66 years; range, 51-88 years). Tumor histologic results included 39 endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 dedifferentiated. Sixteen patients received sequential chemotherapy, and 9 received additional vault brachytherapy. Median follow-up was 9 months (IQR, 3-15 months). Of 61 patients, worst acute gastrointestinal tract toxic effects of grade 1 were observed in 33 patients (54%) and of grade 2 in 8 patients (13%). For genitourinary worst toxic effects, grade 1 was observed in 25 patients (41%) and grade 2 in 2 patients (3%). One patient (1.6%) had an acute grade 3 gastrointestinal tract toxic effect of diarrhea at fraction 5 that resolved at follow-up. Only patient-reported diarrhea scores were both clinically (scores ≥10) and statistically significantly worse at fraction 5 (mean [SD] score, 35.76 [26.34]) compared with baseline (mean [SD] score, 6.56 [13.36]; P < .001), but this symptom improved at follow-up. Conclusions and Relevance: Results of this phase 1/2 nonrandomized controlled trial suggest that stereotactic hypofractionated radiation was well tolerated at short-term follow-up for treatment of uterine cancer. Longer follow-up and future randomized studies are needed to further evaluate this treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04866394.

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 Canadian national guideline on the neoadjuvant treatment of invasive breast cancer, including patient assessment, systemic therapy, and local management principles.

PURPOSE: The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. METHODS: An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. RESULTS: Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. CONCLUSIONS: Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.

Does Prophylactic Paraortic Lymph Node Irradiation Improve Outcomes in Women With Stage IIIC1 Endometrial Carcinoma?

PURPOSE: To evaluate the impact of prophylactic paraortic lymph node (PALN) radiation therapy (RT) on clinical outcomes in patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 endometrial cancer (EC). METHODS AND MATERIALS: A multi-institutional retrospective study included patients with International Federation of Obstetrics and Gynecology 2018 stage IIIC1 EC lymph node assessment, status postsurgical staging, followed by adjuvant chemotherapy and RT using various sequencing regimens. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. In addition, propensity score matching was used to estimate the effect of the radiation field extent on survival outcomes. RESULTS: A total of 378 patients were included, with a median follow-up of 45.8 months. Pelvic RT was delivered to 286 patients, and 92 patients received pelvic and PALN RT. The estimated OS and RFS rates at 5 years for the entire cohort were 80% and 69%, respectively. There was no difference in the 5-year OS (77% vs 87%, P = .47) and RFS rates (67% vs 70%, P = .78) between patients treated with pelvic RT and those treated with pelvic and prophylactic PALN RT, respectively. After propensity score matching, the estimated hazard ratios (HRs) of prophylactic PALN RT versus pelvic RT were 1.50 (95% confidence interval, 0.71-3.19; P = .28) for OS and 1.24 (95% confidence interval, 0.64-2.42; P = .51) for RFS, suggesting that prophylactic PALN RT does not improve survival outcomes. Distant recurrence was the most common site of first recurrence, and the extent of RT field was not associated with the site of first recurrence (P = .79). CONCLUSIONS: Prophylactic PALN RT was not significantly associated with improved survival outcomes in stage IIIC1 EC. Distant metastasis remains the most common site of failure despite routine use of systemic chemotherapy. New therapeutic approaches are necessary to optimize the outcomes for women with stage IIIC1 EC.

Dosimetry and outcomes in patients receiving radiotherapy for synchronous bilateral breast cancers.

BACKGROUND: Synchronous bilateral breast cancer (SBBC) is rare and there is little evidence describing organs at risk (OAR) and limits to the heart and lungs caused by radiotherapy (RT). Quantifying mean heart dose (MHD) and mean lung dose (MLD) from RT in this patient cohort may lead to better understanding of doses to OAR and resultant effects on clinical outcomes. The primary objective was to assess median MHD and MLD in SBBC, while secondary aims included analyses of 1) factors associated with MHD and MLD, 2) V5 and V20 values and 3) factors associated with clinical outcomes. METHODS: Patients planned for adjuvant bilateral whole breast/chest wall (WB) RT from a single institution treated in 2011-2018 were included. Median MHD and MLD (Gy) were stratified by hypofractionated (42.56 Gy/16 fractions, HFRT) and conventional fractionation (50 Gy/ 25 fractions, CFRT) and summarized separately based on the following treatments: 1) locoregional RT, WB tangential RT either 2) no boost 3) sequential boost or 4) simultaneous integrated boost. MHD, MLD, lung V5 and V20 values, and demographics were collected. Linear regression analyses identified factors associated with MHD and MLD and factors associated with clinical outcomes. RESULTS: A total of 88 patients were included. The median MHD for HFRT and CFRT was 1.99 Gy and 2.94 Gy, respectively. The median MLD for HFRT and CFRT was 6.00 Gy and 10.08 Gy, respectively. MHD and MLD were significantly associated with the occurrence of a cardiac or pulmonary event post-radiation. Patients who had a mastectomy or tumoral muscle involvement were more likely to develop a local recurrence, metastasis or new primary while patients who had a lumpectomy or tumor with a positive estrogen receptor status were less likely to experience these events. CONCLUSIONS: Further investigation should be conducted to identify SBBC RT techniques that mitigate dose to OARs to improve clinical outcomes in bilateral breast patients.

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer.

PURPOSE: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes. METHODS AND MATERIALS: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. RESULTS: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001. CONCLUSIONS: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.

Stereotactic Body Radiation Therapy (SBRT) for a Patient with a Myocardial Metastasis: A Case Report.

Metastatic lesions of the heart are rare but have the potential to cause significant morbidity. We describe the case of a patient with renal cell carcinoma who presented with shortness of breath and palpitations and was found to have a metastatic myocardial lesion causing arrythmia. He received stereotactic body radiation therapy (SBRT) to alleviate symptoms and provide local control. SBRT planning was executed using a four-dimensional computed tomography (4DCT) scan to account for respiratory and cardiac motion. Images from a planning magnetic resonance imaging (MRI) scan and a gated diagnostic MRI scan of the heart were fused with the 4DCT to assist with delineating the tumour. A dose of 30 Gy in five fractions was delivered without incident. The patient's cardiac MRI at two months post-treatment showed stability of his cardiac lesion. He subsequently died of distant disease progression, without any recurrence of his cardiac symptoms. SBRT may be considered for patients who present with a symptomatic metastatic cardiac lesion.

Substantial lymphovascular space invasion predicts worse outcomes in early-stage endometrioid endometrial cancer.

INTRODUCTION: Substantial as opposed to focal or no lymphovascular space invasion (LVSI) is proposed as an independent adverse prognostic factor in patients with early-stage endometrioid endometrial cancer (EEC). We reviewed outcomes of patients treated with adjuvant vaginal brachytherapy (VB) alone in a single institution, stratified by LVSI extent. METHODS AND MATERIALS: Retrospective review identified Stage I-II EEC patients receiving VB alone from 2010 to 2017. Extent of LVSI was reported as none, focal, or substantial. Kaplan-Meier estimates and Log-Rank test were used to determine significance between variables. Cox proportional hazards model was used for multivariate analyses. RESULTS: In total, 325 patients were identified with a median follow-up of 35 (23-48) months. LVSI was found in 112 patients with extent reported in 78, 45 (58%) had focal, and 33 (42%) substantial LVSI. Estimated disease-free survival for those with substantial LVSI was 73 (57-94)%, focal LVSI 89 (79-100)%, and no LVSI 94 (90-98)% at 48 months (p = 0.012). On multivariate analyses substantial LVSI was the only risk factor predictive of pelvic [HR substantial vs no: 7.2 (1.0-51.6); p = 0.048] and distant failure [HR substantial vs no: 4.4 (1.2-16.3); p = 0.027]. Both high-grade disease [HR 3 vs 1: 5.5 (1.2-25.6); p = 0.031] and extent of LVSI [HR substantial vs no: 4.4 (1.7-11.4); p = 0.002] predicted for worse disease-free survival. DISCUSSION: Substantial LVSI was the strongest adverse prognostic factor for pelvic and distant failure in this cohort of EEC patients receiving adjuvant VB alone, suggesting this subset may benefit from additional adjuvant therapy. This study underscores the importance of quantifying LVSI extent in EEC.

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.

Overall and chemotherapy-free survival following stereotactic body radiation therapy for abdominopelvic oligometastases.

INTRODUCTION: Limited data establish the efficacy and safety of SBRT in the abdominopelvic (AP) space, where SBRT delivery is challenging due to the proximity of radiosensitive luminal gastrointestinal (GI) organs. The aim of this study was to assess clinical outcomes in patients with AP OM treated with SBRT. METHODS: Eligible patients were those with OM (defined as metastases in ≤3 total sites) in the AP space (excluding liver) treated with SBRT. Descriptive statistics and Kaplan-Meier estimates of (LC), progression-free survival (PFS), overall survival (OS) and chemotherapy-free survival (CFS) were performed. RESULTS: Fifty-one patients with 58 AP OM received SBRT between 2011 and 2015. Median follow-up was 21.9 months. All SBRT treatments were delivered in 5 fractions with a median dose of 35 Gy (25-40 Gy). Progression post-SBRT occurred in 38/51 patients (75%), with a median PFS of 4.9 months (95% CI: 2.5-7.5), and 2-year PFS of 29%. Rates of 2-and 4-year LC were 74% and 69%, respectively. Median OS was 42.6 months (95% CI: 31-55). Oligometastatic progression occurred in 21/38 patients, and of those, 48% (10/21) received further SBRT. Resulting 2- and 4-year CFS were 47% and 37%, respectively (median 15.1 months). Nineteen patients (37%) experienced a grade 1 or 2 acute toxicity. One grade 3 (acute) toxicity was observed. No grade 4 or 5 toxicities were detected. CONCLUSIONS: SBRT to AP OM was associated with sustained LC, excellent OS and minimal toxicity. The use of SBRT allowed for prolonged CFS and the salvage of limited-burden distant failures.

A Comparison of Radiation Techniques in Patients Treated With Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer.

PURPOSE: The standard of care in management of patients with good performance status and unresectable stage III non-small cell lung cancer (NSCLC) therapy is concurrent chemoradiation. Newer techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) are replacing 3-dimensional conformal radiation (3DCRT) despite low-quality evidence of improved outcomes. We used population-based data to examine survival outcomes by radiation technique. METHODS AND MATERIALS: A population-based retrospective cohort of patients with stage III NSCLC treated with concurrent chemoradiation from 2009 to 2017 in Ontario were identified. The primary outcome was a comparison of overall survival among 3DCRT, IMRT, and VMAT, calculated using the Kaplan-Meier method and compared using log-rank test. Cox regression was used to investigate effect of radiation type on overall survival adjusted for other covariates. RESULTS: A total of 3872 patients were treated with 3DCRT (n = 1178), IMRT (n = 1847), or VMAT (n = 847). A decline in 3DCRT and increase in VMAT use were observed over time. Median survival in months was 21.2 (95% confidence interval [CI], 20.0-22.8) for 3DCRT, 23.9 (95% CI, 22.3-25.6) for IMRT, and 24.9 (95% CI, 22.5-27.4) for VMAT, but these differences were not statistically significant (P = .06). CONCLUSIONS: Our study demonstrates that survival is not compromised in patients receiving IMRT or VMAT (compared with 3DCRT). Thus, given the potential dosimetric advantages associated with these techniques, VMAT and IMRT are recommended for the management of patients with stage III NSCLC.

Attitudes and beliefs toward the use of stereotactic body radiotherapy in oligometastatic breast cancer: A commentary on a survey of Canadian Medical Oncologists.

Stereotactic body radiotherapy (SBRT) is a highly ablative local therapy which has emerged as part of the treatment paradigm for patients with oligometastatic (OM) breast cancer (defined by 5 or fewer sites). This patient group has demonstrated improved prognosis in some cases and may therefore, benefit from aggressive local treatment. The role of upfront SBRT in newly diagnosed OM breast cancer in addition to systemic therapy is not clear, yet it is being increasingly utilized within the oncology community. The Canadian medical system is an ideal platform in which to investigate SBRT into the OM breast cancer setting, as it is not routinely implemented across centers at this time, as there is potential for robust collaboration between oncologists in the small community to investigate SBRT, and there is limited financial or industry motivation for early SBRT uptake compared with other countries. It is critical therefore to define the optimal patient population and scenarios for which SBRT should be investigated, as well as offered in the interim to Canadian patients. We therefore conducted a survey of Canadian Medical Oncologists, the primary physicians and gatekeepers of patients with OM breast cancer, to characterize their beliefs, opinions, and areas of controversy in the use of SBRT for OM breast cancer.

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.