Evaluating Peer Review of Palliative Radiation Plans at a Canadian Tertiary Care Cancer Center.

INTRODUCTION: Peer review (PR) of palliative-intent radiation plans is an important but understudied component of quality assurance. This retrospective review aims to improve our understanding of palliative PR by examining the characteristics of reviewed plans and peer feedback along with the associated time burden of two different types of PR processes. METHODS: This single-institution, quality assurance project assessed palliative PR between 2018 and 2020. Initially, the PR involved a multi-disciplinary team PR. Subsequently, it transitioned to independent PR by a single physician. Characteristics of reviewed plans and feedback on PR were captured and abstracted. Time requirements of PR were based on self-reported estimates and attendance records. RESULTS: A total of 1942 cases were reviewed, representing 85.7% (1942/2266) of all palliative-intent plans between 2018 and 2020. A total of 41.1% (n=799) were simple (2D/3D) radiation plans while 56.0% (n=1087) were complex (volumetric modulated arc therapy (VMAT) or tomotherapy) plans. Approximately one-third (30.4%, n=590) of all plans were stereotactic treatments. The rate of any peer feedback was 2.3% (n=45), while the rate of a specific recommended or implemented change was 1.2% (n=24) and 0.9% (n=18), respectively. PR before the start of treatment was associated with more frequent recommended (p=0.005) and implemented changes (p=0.008). Most other factors, including plan complexity and use of stereotactic radiation, were not predictive in this analysis. Comparing the independent versus team PR approach, there was no significant difference in recommended or implemented changes. The mean±standard deviation (SD) staff time required per plan reviewed was 36±6 and 37±6 minutes, including 21±6 and 10±6 minutes of physician time, for team and independent PR, respectively. CONCLUSION: This work highlights the high frequency of complex and stereotactic radiation in the palliative setting, along with the importance of timely PR and the potential benefit of reviewing even simple, 2D/3D radiation plans. Additionally, from a process perspective, our work showed that independent PR may require less dedicated physician time.

Stereotactic body radiotherapy for distant metastases to the head and neck.

PURPOSE: To report clinical outcomes for patients with metastatic disease to the head and neck (HN) treated with stereotactic body radiation therapy (SBRT). METHODS: A retrospective review of patients treated with SBRT to HN sites from 2012 to 2020 was conducted. Treatment indications included the following: oligometastases, oligoprogression, and control a dominant area of progression (DAP). Kaplan-Meier method was used to estimate local control (LC), regional control (RC), overall survival (OS), and progression-free survival (PFS). Univariable (UVA) and multivariable analyses (MVA) were performed. Grade 3-4 acute and late toxicities were reported by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty-six patients (58 lesions) were analysed with a median follow-up of 16 months. Primary sites included lung (25.0%), kidney (19.6%), breast (19.6%) and other (35.8%). SBRT indications were as follows: oligometastases (42.9%), oligoprogression (19.6%) and local control of a dominant area of progression (37.5%). Most patients received SBRT to a single neck node (n = 47, 81.0%). Median SBRT dose was 40 Gy (range 25-50 Gy) in five fractions, with a median biologically effective dose (BED10) of 72 Gy (range 37.5-100 Gy). One- and 2-year LC and RC rates were 97.6% and 72.7% as well as 100% and 86.7%, respectively. Median OS was 19.2 months (95% [CI] 14.8-69.4), and median PFS was 7.4 months (95% [CI] 5.2-11.9). The 1-year OS and PFS rates for oligometastases, oligoprogression and DAP were 95.8%, 63.6% and 38.1% (p = 0.0039) as well as 56.5%, 27.3% and 19.1% (p = 0.0004), respectively. On MVA, treatment indication and histology were predictive for OS, while indication and prior systemic therapy were predictive for PFS. Cumulative late grade 3 + toxicity rate was 11.3%, without grade 5 events. CONCLUSION: The use of SBRT for metastatic disease to the HN provided excellent LC rates with low rates of regional failure and an acceptable toxicity profile, highlighting its utility in these patients. Patients with oligometastatic disease had better OS and PFS than others.

Stereotactic Body Radiotherapy for Extracranial Oligometastatic Disease from Head and Neck Primary Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT. METHODS: A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint. RESULTS: Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported. CONCLUSIONS: SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer.

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan-Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively.

Outcomes for oligometastatic head and neck cancer treated with stereotactic body radiotherapy: Results from an international multi-institutional consortium.

BACKGROUND: We report the results of an international multi-institutional cohort of oligometastatic (OMD) head and neck cancer (HNC) patients treated with SBRT. METHODS: Patients with OMD HNC (≤5 metastases) treated with SBRT between 2008 and 2016 at six institutions were included. Treated metastasis control (TMC), progression-free survival (PFS), and overall survival (OS) were analyzed by multivariable analysis (MVA). RESULTS: Forty-two patients with 84 HNC oligometastases were analyzed. The TMC rate at 1 and 2 years were 80% and 66%, with a median time to recurrence of 10.1 months. The median PFS and OS were 4.7 and 23.3 months. MVA identified a PTV point maximum (BED)10 > 100 Gy as a predictor of improved TMC (HR = 0.31, p = 0.034), and a cumulative PTV > 48 cc as having worse PFS (HR = 2.99, p < 0.001). CONCLUSION: Favorable TMC and OS was observed in OMD HNCs treated with SBRT.

Stereotactic or Conventional Radiation for Early-Stage Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Stereotactic ablative radiotherapy (SABR) has been increasingly used for the treatment of inoperable early-stage non-small cell lung cancer (NSCLC). It has been shown to provide promising local control (LC) and toxicity in prospective trials. However, randomized trials have shown conflicting results in terms of whether SABR confers an overall survival (OS) advantage compared to conventionally fractionated radiotherapy (CFRT). A systematic review of Medline and Embase (inception to December 2020) was performed on early-stage NSCLC patients randomized to SABR versus CFRT. Two independent reviewers screened titles, abstracts, and manuscripts. A random-effects model was used to estimate treatment effects. Toxicity outcomes were compared by the Cochran-Mantel-Haenszel test. Individual patient data were digitally approximated and pooled as secondary analysis. The literature search identified 1494 studies, and 16 studies were included for full-text review. Two randomized trials were identified, including a total of 203 patients, of which 115 (57%) received SABR, and 88 (43%) received CFRT. The weighted mean age was 74 years and 48% of patients were male. Most patients had T1 cancers (67%). Stereotactic ablative radiotherapy was not associated with a significant improvement in OS (hazard ratio: 0.84; 95% confidence interval (CI) 0.34-2.08, p=0.71). There was no significant difference in LC between SABR and CFRT (relative risk: 0.59; CI 0.28-1.23, p=0.16). Of the commonly reported adverse events, one grade 4 toxicity of dyspnea was reported for SABR, while all others i.e., grade 3 or higher toxicities were similar. Stereotactic ablative radiotherapy demonstrated less esophagitis, dyspnea, and skin reaction of any grade. Despite widespread adoption and extensive single-arm prospective and retrospective studies suggesting its benefit, this systematic review and meta-analysis of randomized trials fail to confirm improvements in LC, OS, and toxicity profile of SABR over CFRT in early NSCLC. This small study is likely underpowered to detect clinically significant differences.

Mistaken Metastasis: Radiation-Induced Rib Fracture Mimicking Malignancy on Computerized Tomography Case Report.

A 62-year-old woman with a 40-pack-year smoking history and severe chronic obstructive pulmonary disease with early-stage right upper lobe non-small cell lung cancer (NSCLC) was treated with stereotactic ablative radiotherapy (SABR). Two years after treatment, a surveillance computerized tomography scan showed lesions of the posterior 4th and 5th ribs including expansion of the medulla that was unusual and of concern for possible malignant infiltration. A follow-up magnetic resonance imaging (MRI) scan revealed these lesions to be healing fractures post-radiotherapy. Although generally well tolerated, SABR is known to produce inflammatory and fibrotic changes both in-field and in organs at risk, and rib fractures are a well-established adverse event. MRI has high diagnostic accuracy and sensitivity for rib fractures and was able to rule out malignant spread. This case demonstrates the need for regular follow-up following SABR for early-stage NSCLC, as well as the challenge of interpreting indeterminate post-SABR radiography findings.

Medical Assistance in Dying in Oncology Patients: A Canadian Academic Hospital's Experience.

BACKGROUND: Medical assistance in dying (MAID) was legislatively enacted in Canada in June 2016. Most studies of patients who received MAID grouped patients with cancer and non-cancer diagnoses. Our goal was to analyze the characteristics of oncology patients who received MAID in a Canadian tertiary care hospital. METHODS: We conducted a retrospective review of all patients with cancer who received MAID between June 2016 and July 2020 at London Health Sciences Centre (LHSC). We describe patients' demographics, oncologic characteristics, symptoms, treatments, and palliative care involvement. RESULTS: Ninety-two oncology patients received MAID. The median age was 72. The leading cancer diagnoses among these patients were lung, colorectal, and pancreatic. At the time of MAID request, 68% of patients had metastatic disease. Most patients (90%) had ECOG performance status of 3 or 4 before receiving MAID. Ninety-nine percent of patients had distressing symptoms at time of MAID request, most commonly pain. One-third of patients with metastatic or recurrent cancer received early palliative care. The median time interval between the first MAID assessment and receipt of MAID was 7 days. INTERPRETATION: Most oncology patients who received MAID at LHSC had poor performance status and almost all had distressing symptoms. The median time interval between first MAID assessment and receipt of MAID was shorter than expected. Only one-third of patients with metastatic or recurrent cancer received early palliative care. Improving access to early palliative care is a priority in patients with advanced cancer. STUDY REGISTRATION: We received research approval from Western University's Research Ethics Board (REB) with project ID number 115367, and from Lawson's Research Database Application (ReDA) with study ID number 9579.

Spontaneous Remission of Metastatic Castration-Resistant Prostate Cancer: Coley's Toxin Revisited?

Metastatic castration-resistant prostate cancer (mCRPC) is an incurable disease associated with poor survival outcomes. Immunotherapy was first pioneered by William Coley in the early 20th century with the injection of live and heat-killed bacteria. Despite the recent emergence of cancer immunotherapy, mCRPC remains an elusive immune target. Spontaneous remission of mCRPC following microbial infection has not been described in the literature to date. We present evidence of spontaneous biochemical and radiologic regression in a patient with mCRPC following multiple episodes of sepsis.

Research Productivity of Canadian Radiation Oncology Residents: A Time-Trend Analysis.

(1) Background: Research productivity is a mandatory component of Canadian radiation oncology (RO) resident training. To our knowledge, Canadian RO resident research publication productivity has not previously been analysed. (2) Methods: We compiled a 12-year database of RO residents in Canadian training programs who completed residency between June 2005 and June 2016. Resident names and dates of training were abstracted from provincial databases and department websites and were used to abstract data from PubMed, including training program, publication year, journal, type of research, topic and authorship position. Residents were divided into four time periods and the linear trend test evaluated publication rates over time. Univariable and multivariable logistic regression analyses were performed to identify authorship predictors. (3) Results: 227 RO residents representing 363 publications were identified. The majority were first-author publications (56%) and original research (77%). Overall, 82% of first-author, and 80% of any-author articles were published in resident year 4 or higher. Mean number of publications for first-author and any-author positions increased significantly over time (p = 0.016 and p = 0.039, respectively). After adjusting for gender and time period, large institutions (> 3 residents per year) trended toward associations with more first-author publications (odds ratio (OR): 2.44; p = 0.066) and more any-author publications (OR: 2.49; p = 0.052). No significant differences were observed by gender. (4) Conclusions: Canadian RO resident publication productivity nearly doubled over a 12-year period. The majority of publications are released in the last 2 years of residency, and larger residency programs may be associated with more publications. These findings serve as a baseline as programs transition to Competency Based Medical Education (CBME).

Changing nomogram risk zone classification with serial testing after acute acetaminophen overdose: a retrospective database analysis.

CONTEXT: The Rumack-Matthew nomogram stratifies patients into discrete risk zones following acetaminophen (APAP) overdose. Treatment decisions have traditionally been based on the initial risk zone. "Line-crossing" between zones occurs and is poorly understood. The study objective was to characterize line-crossing behavior in acute APAP overdose patients, especially moving from below to above the nomogram treatment threshold. METHODS AND MATERIALS: The study was a secondary analysis of the Canadian Acetaminophen Overdose Study (CAOS) database, a large medical record review of patients hospitalized in eight large Canadian cities (1980-2005) following APAP poisoning. Population consisted of acute APAP overdose patients with at least two serum concentrations performed during hospitalization. Using ordinal logistic regression, we studied the effects of patient demographics, ingestion size/timing, APAP concentrations, time to N-acetylcysteine (NAC), and co-ingestants on a three-level dependent variable: patients whose risk increased two or more zones, those remaining in the same or adjacent zone, and those whose risk fell by two or more zones. RESULTS: Of the 3201 eligible hospitalizations with 7705 APAP concentrations, half (1679, 52.5%) crossed at least one zone (up or down) within 24 h of acute ingestion, including 190 (5.9%), who crossed at least two lines into a higher risk zone, and 516 (16.1%) at least two lines into a lower risk zone. Of the 1251 patients initially below the nomogram treatment line of 150 µg/mL, 131 (10.8%) patients crossed above this line. Being older, male, and co-ingesting opioids, antimuscarinics, or NSAIDs were independently associated with line-crossing. CONCLUSIONS: Patients commonly crossed nomogram risk zones, including from below to above the current treatment threshold. These findings support recommendations for serial APAP testing until the individual risk of hepatic injury is clearly established.

Stereotactic ablative radiation therapy in lung cancer: an emerging standard.

PURPOSE OF REVIEW: Significant advances have been made in the field of stereotactic ablative radiotherapy (SABR) for the treatment of pulmonary neoplasms in recent years. This review aims to summarize recent salient evidence on SABR for early-stage nonsmall cell lung cancer (ES-NSCLC). RECENT FINDINGS: In medically inoperable patients, SABR remains the standard of care. The optimal SABR dosing regimen is being studied. Comparisons with non-SABR radiotherapy regimens with lower doses per fraction revealed benefit of SABR. In operable patients, no prospective clinical trial comparing SABR and surgery has been completed, although multiple trials are currently underway to address this question. SABR is generally cost-effective and safe in most patients, with preserved patient-reported quality of life. However, increased toxicity with SABR is noted in patients with disease close to, or invading the proximal tracheobronchial tree. Significant SABR-related toxicity and mortality is also reported in patients with coexisting interstitial lung disease. Considerations on pathologic confirmation, surveillance and multiple primaries are also addressed. SUMMARY: SABR is an effective and safe treatment for inoperable ES-NSCLC. Ongoing trials and comparative effectiveness research will help to clarify SABR's role in various lung cancer indications going forward.

Systematic review of patient reported quality of life following stereotactic ablative radiotherapy for primary and metastatic liver cancer.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) is a safe and effective modality in patients with liver cancer who are ineligible for other local therapies. However SABR is not current standard of practice and requires further validation. Patient reported quality of life (QOL) is key to this validation, yet no systematic reviews to date have been performed to analyse QOL following liver SABR. QOL is a critical part of therapy evaluation, particularly in disease states with short life expectancy. The purpose of this study was to conduct a systematic review of QOL outcomes for liver SABR. MATERIALS AND METHODS: MEDLINE and EMBASE databases from 1996 to October 2015 were queried to obtain English language studies analysing QOL following liver SABR. Included studies described patient-reported QOL as either a primary or secondary endpoint, and analysed QOL change over time. Studies were screened, and relevant data were abstracted and analysed. RESULTS: Of 2181 initially screened studies, 5 met all inclusion criteria. Extracted studies included a total of 392 eligible patients with hepatocellular carcinoma, liver metastases and intrahepatic cholangiocarcinoma. Four studies were prospective in design, and only one study was a conference abstract. Extracted studies were heterogeneous in dose prescription used (11-70 Gy in 3-30 fractions), in addition to reported QOL metrics (EORTC QLQ C-15 PAL,/C-30/LM-21, EuroQol 5D, FACT-Hep, FLIC) and final endpoints (range 6 weeks to 12 months). Despite this there were few statistically significant declines in QOL scores following SABR. Four studies demonstrated transient fatigue in the first 1-4 weeks, while 2 studies showed transient worsening of appetite at 1 month. In all but one instance (loss of appetite at 6 weeks), levels returned to insignificant difference baseline by the final endpoints. All studies showed no significant QOL decline in any domain at their respective endpoints. In studies with overlapping QOL tools, estimates of 3-month post SABR global QOL were similar. CONCLUSION: Results of this systematic review demonstrate well-preserved post liver SABR QOL. These findings strengthen the argument for liver SABR, and should aim to support future comparative effectiveness trials with other local modalities including surgery, chemoembolization and radiofrequency ablation, with a focus on QOL outcomes as an important endpoint.

Distress in Caregivers Accompanying Patients to an Emergency Department: A Scoping Review.

BACKGROUND: Despite substantial research interest in caregiver distress in the emergency department (ED), no recent review of the literature exists. OBJECTIVE: Our aims were to map primary research on caregiver distress in the ED, synthesize key concepts underpinning the literature, identify gaps, and provide guidance for future work. METHODS: We used a five-stage scoping review with tandem screening and data extraction. RESULTS: Of 2121 records, 29 studies were included. The majority were small, conducted in North America or Europe, and published after 2000. Numerous methodologies and definitions of distress were represented. The majority involved children, with just five studies restricted to adults. Many involved higher-acuity scenarios, such as resuscitations or invasive procedures. The most common research topic was anxiety of parents of children undergoing procedures. Effects of witnessed resuscitation were also addressed. Parental presence may reduce anxiety during venipuncture, while only waiting room music reduced anxiety in parents of children not undergoing a procedure. No study explored interventions to reduce distress in caregivers of adults. While heterogeneity precluded evidence-based recommendations, clinically relevant observations emerged, including that anxiety can be worsened if a caregiver believes their patient has been forgotten; that parents are sensitive about being perceived as neglectful; and that sympathy and confidence ease distress, as does sensitivity toward end-of-life issues. Several studies suggested that negative staff behaviors affect caregiver anxiety. CONCLUSIONS: Future studies should use validated measures of distress; include larger samples; and capture adult, geriatric, and rural populations. A focused systematic review might yield evidence-based guidance for clinicians.

Relationship between family caregiver burden and physical frailty in older adults without dementia: a systematic review.

BACKGROUND: Physical frailty is a prevalent syndrome in older adults that increases vulnerability for a range of adverse outcomes including increased dependency and death. Caregivers of older adults experience significant physical, emotional, and financial burden, which is associated with poor physical and mental health. While it is known that care recipients' dementia is associated with burden, the literature regarding the impact of physical frailty on burden has yet to be synthesized. We conducted a systematic review to assess the state of the evidence regarding the relationship between these two prominent concepts in the geriatric literature. METHOD: We used a structured search of databases to identify original English-language articles. Two researchers screened the titles and abstracts of all 1202 retrieved studies and then full-text versions of 265 retained studies. Screening was based on a priori inclusion criteria, which included discussion of physical frailty, caregiver burden, and a population of community-dwelling older adults without dementia. Nine included papers underwent data abstraction and critical appraisal using the Cochrane Risk of Bias Tool or the Newcastle-Ottawa Scale (for randomized controlled trials or cross-sectional studies, respectively). Heterogeneity of the included studies precluded meta-analysis. RESULTS: Five publications had the same author and drew from the same population; these were treated as a single study. Three of our studies were of limited value since they did not include a validated measure of frailty. While caregivers of frail older adults experience burden, the scarce available evidence and lack of studies comparing this population with normative values does not allow conclusions to be drawn about the strength or nature of the relationship. Judging from excluded studies, the term "frailty" is often used without reference to a clear definition or is treated as synonymous with functional impairment or advanced age. CONCLUSIONS: Our review suggests that caregivers of frail older adults experience burden and that the degree of burden may differ from that of other caregiver populations. The limited evidence does not allow conclusions to be drawn or to inform clinical practice. Further research is needed, given the salience of physical frailty and burden. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019198.