Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Population-based phase II trial of stereotactic ablative radiotherapy (SABR) for up to 5 oligometastases: SABR-5.

BACKGROUND: Oligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1-3 or 1-5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates. METHODS: This is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity. DISCUSSION: SABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials. TRIAL REGISTRATION: Registered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.

Re-irradiation volumetric modulated arc therapy optimization based on cumulative biologically effective dose objectives.

The objective of this note is to introduce a clinical tool that generates ideal base plan dose distributions to enable re-irradiation volumetric modulated arc therapy (VMAT) optimization based on cumulative biological effective dose objectives for specific organs at risk (OARs). The tool is demonstrated with a lung cancer case that required re-irradiation at our clinic. First, previous treatment dose is deformed onto the retreatment computed tomography (CT) using commercial software. Then, the in-house Matlab tool alters the deformed previous dose using radiobiological concepts on a voxel-by-voxel manner to generate an ideal base plan dose distribution. Ideal base plans that were generated using the in-house Matlab tool were compatible with the Varian Eclipse™ treatment planning system. The tool enabled optimization of VMAT re-irradiation plans using cumulative dose limits for OARs and all OAR cumulative dose objectives were met on the first optimization for the recurrent lung cancer case tested.

The Vancouver rapid access clinic for palliative lung radiation, providing more than just rapid access.

PURPOSE: The Vancouver Rapid Access (VARA) clinic aimed to deliver urgent palliative radiotherapy (RT) and holistic care to patients with newly diagnosed incurable lung cancer. The purpose of this paper is to describe the 9-month pilot phase of the clinic and to compare its efficacy to standard practice. METHODS: A multidisciplinary team performed the initial consult, and if appropriate, the patient received RT the same day and was connected with supportive services as required. Patient and treatment details were prospectively collected. A retrospective chart review of similar patients in standard practice 1 year prior to VARA was performed. Variables compared between VARA and standard practice included RT wait times and supportive service referrals. RESULTS: During the pilot phase, 58 patients were assessed. Forty percent were inpatients, and 62% had an ECOG 2 or higher. Fifty-four patients received RT; the majority (72%) received RT on the same day as their consultation, compared to 41% in standard practice (p < 0.001). The most common sites treated were the bone (42%), lung (34%), and brain (14%). More than half of VARA patients (54%) were referred to an additional health service such as home care nursing compared to 31% of standard practice patients (p = 0.01). The VARA clinic decreased the proportion of patients double-booked into an oncologists schedule from 23 to 13% (p < 0.001). CONCLUSIONS: The VARA clinic has improved wait times for palliative RT, increased patient access to supportive services, and improved the workload for lung radiation oncologists. This clinic could serve as a model for other patients with incurable cancer.

Upfront Versus Delayed Systemic Therapy in Patients With Oligometastatic Cancer Treated With SABR in the Phase 2 SABR-5 Trial.

PURPOSE: The optimal sequencing of local and systemic therapy for oligometastatic cancer has not been established. This study retrospectively compared progression-free survival (PFS), overall survival (OS), and SABR-related toxicity between upfront versus delay of systemic treatment until progression in patients in the SABR-5 trial. METHODS AND MATERIALS: The single-arm phase 2 SABR-5 trial accrued patients with up to 5 oligometastases across SABR-5 between November 2016 and July 2020. Patients received SABR to all lesions. Two cohorts were retrospectively identified: those receiving upfront systemic treatment along with SABR and those for whom systemic treatment was delayed until disease progression. Patients treated for oligoprogression were excluded. Propensity score analysis with overlap weighting balanced baseline characteristics of cohorts. Bootstrap sampling and Cox regression models estimated the association of delayed systemic treatment with PFS, OS, and grade ≥2 toxicity. RESULTS: A total of 319 patients with oligometastases underwent treatment on SABR-5, including 121 (38%) and 198 (62%) who received upfront and delayed systemic treatment, respectively. In the weighted sample, prostate cancer was the most common primary tumor histology (48%) followed by colorectal (18%), breast (13%), and lung (4%). Most patients (93%) were treated for 1 to 2 metastases. The median follow-up time was 34 months (IQR, 24-45). Delayed systemic treatment was associated with shorter PFS (hazard ratio [HR], 1.56; 95% CI, 1.15-2.13; P = .005) but similar OS (HR, 0.90; 95% CI, 0.51-1.59; P = .65) compared with upfront systemic treatment. Risk of grade 2 or higher SABR-related toxicity was reduced with delayed systemic treatment (odds ratio, 0.35; 95% CI, 0.15-0.70; P < .001). CONCLUSIONS: Delayed systemic treatment is associated with shorter PFS without reduction in OS and with reduced SABR-related toxicity and may be a favorable option for select patients seeking to avoid initial systemic treatment. Efforts should continue to accrue patients to histology-specific trials examining a delayed systemic treatment approach.

Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial.

PURPOSE: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of SABR to standard of care (SOC) systemic therapy. METHODS AND MATERIALS: We enrolled patients with 1 to 5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs noncytotoxic), randomized 1:2 between continued SOC treatment versus SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all nonhematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events, and duration of systemic therapy postrandomization. RESULTS: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. The median age was 67 years, and 39 (43%) were women. The most common primary sites were lung (44%), genitourinary (23%), and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. The median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs 4.3 months in the SOC arm, but curves cross and 2-year PFS was 9% vs 24%, respectively; P = .91). The median OS was 31.2 months versus 27.4 months, respectively (P = .22). Lesional control was superior with SABR (70% vs 38%, respectively; P = .0015). There were 2 (3.4%) grade 3 and no grade 4/5 adverse events attributable to SABR. CONCLUSIONS: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Should organs at risk (OARs) be prioritized over target volume coverage in stereotactic ablative radiotherapy (SABR) for oligometastases? a secondary analysis of the population-based phase II SABR-5 trial.

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS). METHODS: This single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated. RESULTS: 549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86-0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93-0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69-0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and 'other' (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS. CONCLUSION: PTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning.

Predictors of Early Polymetastatic Relapse After SABR for up to 5 Oligometastases: A Secondary Analysis of the Phase II SABR-5 Trial.

PURPOSE: A subset of patients with oligometastatic cancer experience early widespread cancer dissemination and do not benefit from metastasis-directed therapy such as SABR. This study aimed to identify factors associated with early polymetastatic relapse (PMR). METHODS AND MATERIALS: The SABR-5 trial was a single arm phase 2 study conducted at all 6 regional cancer centers across British Columbia (BC), Canada. SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastatic lesions (total, progressing, or induced) received SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2 and life expectancy ≥6 months. This secondary analysis evaluated factors associated with early PMR, defined as disease recurrence within 6 months of SABR, which is not amenable to further local treatment. Univariable and multivariable analyses were performed using binary logistic regression. The Kaplan-Meier method and log-rank tests assessed PMR-free survival and differences between risk groups, respectively. RESULTS: Between November 2016 and July 2020, 381 patients underwent treatment on SABR-5. A total of 16% of patients experienced PMR. Worse performance status (Eastern Cooperative Oncology Group 1-2 vs 0; hazard ratio [HR] = 2.01, P = .018), nonprostate/breast histology (HR = 3.64, P <.001), and oligoprogression (HR = 3.84, P <.001) were independent predictors for early PMR. Risk groups were identified with median PMR-free survival ranging from 5 months to not yet reached at the time of analysis. Rates of 3-year overall survival were 0%, 53% (95% confidence interval [CI], 48-58), 77% (95% CI, 73-81), and 93% (95% CI, 90-96) in groups 1 to 4, respectively (P <.001). CONCLUSIONS: Four distinct risk groups for early PMR are identified, which differ significantly in PMR-free survival and overall survival. The group with all 3 risk factors had a median PMR-free survival of 5 months and may not benefit from local ablative therapy alone. This model should be externally validated with data from other prospective trials.

Progression-Free Survival and Local Control After SABR for up to 5 Oligometastases: An Analysis From the Population-Based Phase 2 SABR-5 Trial.

PURPOSE: Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial. METHODS AND MATERIALS: The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here. RESULTS: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P = .003), 4 or more metastases at SABR (HR, 1.48; P = .048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P = .008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P = .002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC. CONCLUSIONS: In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm.

Treatment With Stereotactic Ablative Radiotherapy for Up to 5 Oligometastases in Patients With Cancer: Primary Toxic Effect Results of the Nonrandomized Phase 2 SABR-5 Clinical Trial.

Importance: After the publication of the landmark SABR-COMET trial, concerns arose regarding high-grade toxic effects of treatment with stereotactic ablative body radiotherapy (SABR) for oligometastases. Objective: To document toxic effects of treatment with SABR in a large cohort from a population-based, provincial cancer program. Design, Setting, and Participants: From November 2016 to July 2020, 381 patients across all 6 cancer centers in British Columbia were treated in this single-arm, phase 2 trial of treatment with SABR for patients with oligometastatic or oligoprogressive disease. During this period, patients were only eligible to receive treatment with SABR in these settings in trials within British Columbia; therefore, this analysis is population based, with resultant minimal selection bias compared with previously published SABR series. Interventions: Stereotactic ablative body radiotherapy to up to 5 metastases. Main Outcomes and Measures: Rate of grade 2, 3, 4, and 5 toxic effects associated with SABR. Findings: Among 381 participants (122 women [32%]), the mean (SD; range) age was 68 (11.1; 30-97) years, and the median (range) follow-up was 25 (1-54) months. The most common histological findings were prostate cancer (123 [32%]), colorectal cancer (63 [17%]), breast cancer (42 [11%]), and lung cancer (33 [9%]). The number of SABR-treated sites were 1 (263 [69%]), 2 (82 [22%]), and 3 or more (36 [10%]). The most common sites of SABR were lung (188 [34%]), nonspine bone (136 [25%]), spine (85 [16%]), lymph nodes (78 [14%]), liver (29 [5%]), and adrenal (15 [3%]). Rates of grade 2, 3, 4, and 5 toxic effects associated with SABR (based on the highest-grade toxic effect per patient) were 14.2%; (95% CI, 10.7%-17.7%), 4.2% (95% CI, 2.2%-6.2%), 0%, and 0.3% (95% CI, 0%-0.8%), respectively. The cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 by Kaplan-Meier analysis was 8%, and for grade 3 or higher, 4%. Conclusions and Relevance: This single-arm, phase 2 clinical trial found that the incidence of grade 3 or higher SABR toxic effects in this population-based study was less than 5%. Furthermore, the rates of grade 2 or higher toxic effects (18.6%) were lower than previously published for SABR-COMET (29%). These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and potentially support further enrollment in randomized phase 3 clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02933242.

Prospective comparison of two cognitive screening tests: diagnostic accuracy and correlation with community integration and quality of life.

Cognitive screening tests are frequently used in brain tumor clinics. The Mini Mental State Examination (MMSE) is the most commonly used, and the Montreal Cognitive Assessment (MoCA) is an alternative. This study compares the diagnostic accuracy of both screening tests. Fifty-eight patients with brain tumors were prospectively accrued and administered the MMSE and MoCA, 67% of who completed a comprehensive neuropsychological evaluation as a gold standard comparison. Quality of life and community integration were measured with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Community Integration Questionnaire (CIQ), respectively. At the pre-defined cut-off scores, the MoCA had superior sensitivity (61.9% vs. 19.0%, P < 0.005) and the MMSE had superior specificity (94.4% vs. 55.6%, P < 0.017). The areas under the ROC curve for the MMSE (0.615, standard error = 0.091) and MoCA (0.606, standard error = 0.092) were poor, indicating that at no single cut-off score is either test both sensitive and specific. Neither the MMSE (ρ = 0.12; P < 0.444) nor MoCA (ρ = 0.24; P < 0.108) were significantly correlated with the FACT-Br. The MoCA was modestly correlated with the CIQ (ρ = 0.35; P < 0.017), but the MMSE was not (ρ = 0.14; P < 0.359). The MMSE has extremely poor sensitivity. Using this test in clinical practice, research, and clinical trials will result in failing to detect cognitive impairment in a substantial percentage of patients. The MoCA has superior sensitivity, and is better correlated with self reported measures of community integration, and therefore should be preferentially chosen in practice and clinical trials.

Prospective comparison of the prognostic utility of the Mini Mental State Examination and the Montreal Cognitive Assessment in patients with brain metastases.

PURPOSE: The Mini Mental State Examination (MMSE) is the most commonly chosen cognitive screening test (CST) in clinical practice and trials, despite its poor sensitivity, likely because of its prognostic utility. The Montreal Cognitive Assessment (MoCA) is an alternative CST, is more sensitive, and is better correlated with quality of life. METHODS: Sixty-five patients with brain metastases were prospectively accrued and completed both the MMSE and MoCA. We compared the prognostic utility of both CSTs. RESULTS: The mean age of patients was 59.0 years; 42.0% had single brain metastases. Median MMSE and MoCA scores were 28 and 22, respectively. Median overall survival (OS) was worse for individuals with below- versus above-average MMSE scores (10.4 versus 36.3 weeks, p = 0.007). Likewise, below- versus above-average MoCA scores were prognostic (6.3 versus 50.0 weeks, p < 0.001). Median OS for MoCA scores <22, 22-26, and >26 were 6.3, 30.9, and 61.7 weeks, respectively (p < 0.001). On multivariable analysis, below-average MMSE scores were no longer prognostic (hazard ratio [HR] = 1.71 [0.90-3.26]), though below-average MoCA scores were (HR = 5.44 [2.70-10.94]). Furthermore, the MoCA demonstrated superior prognostic utility when comparing multivariable models with continuous CST scores. CONCLUSIONS: Our results indicate that the MoCA is a superior prognostic indicator than the MMSE. Furthermore, given its superior sensitivity and better correlation with quality of life, the MoCA should be preferentially chosen in clinical practice and trials.

Radiation Oncology Resident and Program Director Perceptions of the Job Market and Impact on Well-being.

Background Radiation oncology graduates occasionally experience difficulties obtaining employment. The purpose of this study was to explore the perceptions of radiation oncology residents (RORs) and program directors (PDs) about the job market and the potential impact on their well-being. Methods RORs and PDs from 13 Canadian training programs were invited to participate. Semi-structured interviews were conducted from March 2014 to January 2015. Knowledge/perception of the job market, impact on personal/professional life, as well as opinions regarding possible contributing factors/solutions to the job market were assessed. A conventional content analysis of each transcript was performed with the clustering of conceptually similar expressions into themes. Demographic information was summarized with descriptive statistics. Results Twenty RORs and four PDs participated. All the participants described delayed retirement and over-training as contributors to the job shortage. The majority of trainees interviewed were concerned about the job market (60%) and reported that it impacted their personal (60%) and professional (55%) relationships. PDs described the job market as negatively impacting their job satisfaction. Resident morale was ranked as poor by both groups. Conclusions Job market shortages can negatively impact the personal and professional well-being of trainees and PDs. Attention to manpower planning is important to maintaining a high-quality workforce. The cyclical undersupply and oversupply of residents occur in several countries, which makes our findings potentially relevant to residency training programs internationally.

A Patient-centered Approach to Evaluate the Information Needs of Women With Ductal Carcinoma In Situ.

OBJECTIVE: To evaluate the information needs of ductal carcinoma in situ (DCIS) patients. METHODS: Four focus groups involving 24 previously treated DCIS patients were conducted to develop a comprehensive list of questions they felt were important to have answered at the time of diagnosis. Using a survey, a separate group of patients treated for DCIS then rated the importance of having each of these questions addressed before treatment decision making. Response options were "essential," "desired," "not important," "no opinion," and "avoid." For each essential/desired question, respondents specified how addressing it would help them: "understand," "decide," "plan," "not sure," or "other." RESULTS: Focus group participants generated 117 questions used in the survey. Fifty-seven patients completed the survey (55% response rate). Respondents rated a median of 66 questions as essential. The most commonly cited reason for rating a question essential was to "understand," followed by to "decide." The top questions women deemed essential to help them understand were disease specific, whereas the top questions deemed essential to help women decide were predominantly treatment specific, pertaining to available options, recurrence and survival outcomes, and timelines to decide and start treatment. CONCLUSIONS: DCIS patients want a large number of questions answered, mostly for understanding, and also for deciding and planning. A core set of questions that most patients consider essential for decision making has been formulated and may be used in the clinical setting and in research to develop educational resources and decision-making tools specific to DCIS.

Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study.

PURPOSE: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). METHODS AND MATERIALS: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with ClinicalTrials.gov (clinicaltrials.gov identifier NCT01046123). RESULTS: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. CONCLUSIONS: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.

Does the incidence and outcome of brain metastases in locally advanced non-small cell lung cancer justify prophylactic cranial irradiation or early detection?

OBJECTIVE: The radical treatment of locally advanced non-small cell lung cancer (LA-NSCLC) currently involves combined modality therapy (CMT) with the use of chemotherapy in addition to radiation therapy and/or surgery. Chemotherapy has been shown to improve survival, but does not alter brain relapse. We reviewed the outcomes of Stage IIIA and IIIB LA-NSCLC patients treated with CMT at our institution. We assessed the incidence of brain metastases and the management and outcome of these patients. METHODS: Using our radiation-planning database (RSTS), we identified 230 consecutive patients from the years 1999 and 2000 who received radical radiation therapy to the lung. Extracting data from the chart, we identified 83 patients who were treated radically with chemotherapy, radiation and possibly surgery. These patients form the basis of this study. RESULTS: At 2 years, the actuarial rates for any brain failure, first failure in the brain and sole failure in the brain were 34.2%, 24.6% and 11.0%, respectively. Age was the only factor among sex, histology, stage, weight loss and the timing of chemotherapy and radiation that predicted for an increased risk of first failure in the brain. Patients less than age 60 had a risk of 25.6% versus 11.4% for those greater than 60 (p = 0.022). Among the patients who failed first in the brain, those who had aggressive management of their brain metastases with surgical resection in addition to whole brain radiotherapy had a median survival of 26.3 months compared with 3.3 months for those treated with palliative whole brain radiotherapy alone. CONCLUSION: Brain metastases are common in patients with LA-NSCLC treated with CMT. These patients may benefit from either prophylactic cranial irradiation or early detection and aggressive treatment of brain metastases.

The impact of peer review of volume delineation in stereotactic body radiation therapy planning for primary lung cancer: a multicenter quality assurance study.

INTRODUCTION: Although the value of peer review is increasingly recognized, there is little research documenting its impact in the setting of stereotactic body radiation therapy (SBRT) for lung cancer. This study determines the dosimetric effect of peer review of tumor and normal tissue contouring in lung SBRT planning. METHODS: Forty anonymized lung SBRT plans were retrospectively evaluated post treatment. Each plan was independently reviewed by two to three radiation oncologists using established institutional guidelines. For each structure, reviewers recorded recommendations for "no change," "minor change," "major change," or "missing contour" and provided a modified or new contour as needed. Dose-volume histograms were analyzed for dosimetric violations. RESULTS: Among 472 contoured structures evaluated, recommendations from peer review were 107 major change (23%), 176 minor change (37%), 157 no change (33%), and 32 missing (7%). Common major changes involved the skin (n = 20), heart (n = 18), and proximal bronchial tree (n = 15). Dose constraints were not achieved for 25 new or recontoured structures (5%), of which 17 involved the planning target volume (PTV). Among cases with PTV violations, the mean prescription dose coverage to the modified PTVs was 90%, compared with the protocol standard of greater than or equal to 95% coverage. The remaining violations involved the ribs (n = 5), spinal canal (n = 2), and heart (n = 1). CONCLUSIONS: Peer review of structure contouring resulted in significant changes in lung SBRT plans. Recontouring of several plans revealed violations of dose limits, most often involving inadequate PTV coverage. Peer review, especially of target volume delineation, is warranted to improve consistency and quality in lung SBRT planning.

Thymoma: a population-based study of the management and outcomes for the province of British Columbia.

INTRODUCTION: Thymomas are rare neoplasms with variable clinical behavior. Our primary study aim was to analyze treatment practices and outcomes in a population-based cohort of thymoma patients. We hypothesized that stage I and II thymomas would have high cure rates with resection and adjuvant radiation, whereas locally advanced cases would benefit from multimodality therapy. METHODS: All patients, diagnosed with thymoma or thymic carcinoma in British Columbia between 1994 and 2009, were identified using the British Columbia Cancer Agency Registry. Chart review was used to collect demographic and treatment data. Detailed pathology review was performed using the World Health Organization classification. RESULTS: One hundred and seventy-one patients were identified for analysis. The 5-year overall survival was 93.3%, 88.7%, 74.6%, 43.4% for stages I, II, III, and IV, respectively. Survival varied significantly among patients with thymoma compared with thymic carcinoma. In patients with stage II disease, adjuvant radiation did not confer an overall survival or recurrence-free survival benefit. Seventy-five patients had locally advanced disease. There was practice variation in treatment of these patients. Patients with thymoma undergoing trimodality treatment had a 5-year median overall survival of 80%, whereas patients with thymic carcinoma had poor outcomes despite aggressive treatment. CONCLUSIONS: Survival rates in this population-based series were comparable to those in previously published reports. The ideal management of thymic tumors involves a multidisciplinary approach, particularly in locally advanced disease and selection of patients for adjuvant radiation therapy.

Information needs of post-menopausal women with hormone receptor positive early-stage breast cancer considering adjuvant endocrine therapy.

OBJECTIVE: To identify questions that post-menopausal women with receptor-positive early-stage breast cancer want answered before their adjuvant-endocrine-therapy decision is made. METHODS: We surveyed patients eligible for adjuvant-endocrine therapy in the previous 3-18 months. Participants rated the importance of getting each of 95 questions answered before the decision is made (options: essential/desired/not important or no opinion/avoid). For each question rated "essential"/"desired", the participant also identified the purpose(s) for the answer: to help her understand, decide, plan, or other reason(s). RESULTS: The response rate was 55% (188/343). Participants rated a mean of 57 (range: 1-95) questions "essential", 80 (range: 1-95) "essential" or "desired", and 2 (range: 0-27) "avoid". Every question was "essential" to ≥31% of participants, and "essential"/"desired" to ≥63%. All but eleven questions were rated as "avoid" by ≥1 participant. The most frequent purposes for "essential" questions were to: understand their situations (mean 45, range: 0-95), decide (mean 18, range: 0-94), and plan (mean 13, range: 0-95). CONCLUSION: Many patients want a lot of information before this decision is made but there is wide variation within the group in both the number and in which questions they want answered. PRACTICE IMPLICATIONS: Patient education in this setting needs to be tailored to the needs of the individual patient.

Information for decision making by post-menopausal women with hormone receptor positive early-stage breast cancer considering adjuvant endocrine therapy.

PURPOSE: To identify the information that post-menopausal women with hormone-receptor positive, early-stage breast cancer want, to help them decide among six treatment options for adjuvant-endocrine therapy. METHODS: We surveyed women with early-stage breast cancer who were eligible for adjuvant endocrine-therapy 3-18 months earlier. Participants rated the importance of getting each of 95 questions answered before this decision is made (options: essential/desired/not important/avoid). For questions rated essential or desired, participants identified the purpose(s) for having the question answered: to help them understand, make the decision, plan, or other. Participants indicated the role they played in their actual decision and the role they would prefer if the decision was made today. They also indicated whether they felt they had had a choice of endocrine therapy treatments. RESULTS: 188 of 343 questionnaires were returned (response rate 55%). Mean age was 67 yr (range 38-88 yr); 76% were married, and 39% had secondary school education or less. On average, respondents rated 18 questions (range 0-94) essential for decision making. Each question was rated essential for decision making by ≥ 7% of participants but only 1 question by >50%. Regarding roles, 89% of respondents had participated in their actual decision and would want to again; an additional 9% had not participated in their actual decision but would want to at the time of the survey. The percentage of respondents who felt they had no choice of endocrine therapy treatments varied between centres, 25% vs 41% and 49%. CONCLUSIONS: Most patients want to participate in the decision but they vary widely in the amount and which specific details they want to help them make the decision. IMPLICATION: The wide variation in questions considered important means the support should be tailored to the needs of the individual patient.