The management of stage I Non-Small cell lung cancer (NSCLC) in Ontario: A Population-Based study of patterns of care and Stereotactic Ablative Body radiotherapy (SABR) utilization from 2010 to 2019.

BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is the standard of care for medically inoperable patients with Stage I NSCLC. The adoption of SABR and its association with cancer outcomes requires characterization. AIM: We described the management of biopsy-proven Stage I NSCLC with SABR, surgery, non-SABR curative radiotherapy (RT) and observation in Ontario, Canada, between 2010 and 2019. Temporal and geographic trends in practice and survival outcomes were analyzed. METHODS: This was a retrospective population-based cohort study conducted by linking electronic radiotherapy (RT) records to a population-based cancer registry. RESULTS: A total of 12,065 patients were identified, 61.7 % underwent surgery, 17.9 % received SABR, 8.6 % received non-SABR curative RT and 11.7 % were observed. Between 2010 and 2019, the utilization of surgery decreased (63.8 % to 49.9 %, p < 0.0001), while SABR use increased (7.5 % to 24.4 %, p < 0.0001), non-SABR curative RT use increased (6.7 % to 9.6 %, p < 0.0014) and patients observed decreased (14.4 % to 12.0 %, p < 0.0001). Substantial variation in practice exists across Ontario. Two- yr CSS improved for the entire cohort (81.9 % to 85.0 %, p < 0.0001). While there was improvement in 2 yr CSS for surgical patients (92.1 %% to 95.7 %, p < 0.001), survival for patients who received SABR, Non-SABR curative RT and observation remained stable. CONCLUSION: There has been an increase in SABR utilization and a reduction in surgical utilization with a corresponding increased survival of stage I patients in Ontario between 2010 and 2019. Substantial differences in practice patterns exist across health regions, suggesting the need for strategies to improve access to SABR in many jurisdictions.

Survival outcomes and predicting intracranial metastasis in stage III non-small cell lung cancer treated with definitive chemoradiation: Real-world data from a tertiary cancer center.

PURPOSE/OBJECTIVE: Around 30% of patients with non-small cell lung cancers (NSCLC) are diagnosed with stage III disease at presentation, of which about 50% are treated with definitive chemoradiation (CRT). Around 65-80% of patients will eventually develop intracranial metastases (IM), though associated risk factors are not clearly described. We report survival outcomes and risk factors for development of IM in a cohort of patients with stage III NSCLC treated with CRT at a tertiary cancer center. MATERIALS/METHODS: We identified 195 patients with stage III NSCLC treated with CRT from January 2010 to May 2021. Multivariable logistic regression was used to generate odds ratios for covariates associated with development of IM. Kaplan-Meier analysis with the Log Rank test was used for unadjusted time-to-event analyses. P-value for statistical significance was set at < 0.05 with a two-sided test. RESULTS: Out of 195 patients, 108 (55.4%) had stage IIIA disease and 103 (52.8%) had adenocarcinoma histology. The median age and follow-up (in months) was 67 (IQR 60-74) and 21 (IQR 12-43), respectively. The dose of radiation was 60 Gy in 30 fractions for148 patients (75.9%). Of the 77 patients who received treatment since immunotherapy was available and standard at our cancer center, 45 (58.4%) received at least one cycle. During follow-up, 84 patients (43.1%) developed any metastasis, and 33 (16.9%) developed IM (either alone or with extracranial metastasis). 150 patients (76.9%) experienced a treatment delay (interval between diagnosis and treatment > 4 weeks). Factors associated with developing any metastasis included higher overall stage at diagnosis (p = 0.013) and higher prescribed dose (p = 0.022). Factors associated with developing IM included higher ratio of involved over sampled lymph nodes (p = 0.001) and receipt of pre-CRT systemic or radiotherapy for any reason (p = 0.034). On multivariate logistical regression, treatment delay (OR 3.9, p = 0.036) and overall stage at diagnosis (IIIA vs. IIIB/IIIC) (OR 2.8, p = 0.02) predicted development of IM. These findings were sustained on sensitivity analysis using different delay intervals. Median OS was not reached for the overall cohort, and was 43.1 months for patients with IM and 40.3 months in those with extracranial-only metastasis (p = 0.968). In patients with any metastasis, median OS was longer (p = 0.003) for those who experienced a treatment delay (48.4 months) compared to those that did not (12.2 months), likely due to expedited diagnosis and treatment in patients with a higher symptom burden secondary to more advanced disease. CONCLUSIONS: In patients with stage III NSCLC treated with definitive CRT, the risk of IM appears to increase with overall stage at diagnosis and, importantly, may be associated with experiencing a treatment delay (> 4 weeks). Metastatic disease of any kind remains the primary life-limiting prognostic factor in these patients with advanced lung cancer. In patients with metastatic disease, treatment delay was associated with better survival. Patients who experience a treatment delay and those initially diagnosed at a more advanced overall stage may warrant more frequent surveillance for early diagnosis and treatment of IM. Healthcare system stakeholders should strive to mitigate treatment delay in patients with locally NSCLC to reduce the risk of IM. Further research is needed to better understand factors associated with survival, treatment delay, and the development of IM after CRT in the immunotherapy era.

A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis.

Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

Improving Timeliness of Oncology Assessment and Cancer Treatment Through Implementation of a Multidisciplinary Lung Cancer Clinic.

PURPOSE: Timely lung cancer care has been associated with improved clinical outcomes and patient satisfaction. We identified improvement opportunities in lung cancer management pathways at Kingston Health Sciences Centre. Quality improvement strategies led to the implementation of a multidisciplinary lung cancer clinic (MDC). METHODS: We set an outcome measure of decreasing the time from diagnosis to first cancer treatment by 10 days within 6 months of clinic implementation. We implemented a weekly MDC that involved respirologists, medical oncologists, and radiation oncologists at which patients with new lung cancer diagnoses were offered concurrent oncology consultation. We used Plan-Do-Study-Act cycles to guide our improvement initiatives. A total of five Plan-Do-Study-Act cycles spanned 14 months and consisted of an MDC pilot clinic, large-scale MDC launching, debriefing meetings, and clinic expansion. Pre-MDC data were analyzed retrospectively to establish baseline and prospectively for improvement. Statistical Process Control XmR(i) charts were used to report data. RESULTS: Since MDC initiation, 128 patients have been seen in 34 MDC clinics (3.8 patients per clinic). Mean days from diagnosis to first oncology assessment decreased from 12.4 days to 3.9 days, and mean days from diagnosis to first cancer treatment decreased from 39.5 to 15.0 days, both of which demonstrated special cause variation. Time to assessment and treatment improved for patients with every stage of lung cancer and for both small-cell and non-small-cell subtypes. CONCLUSION: MDC shortens the time from lung cancer diagnosis to oncology assessment and treatment. Time to treatment improved more than time to oncology assessment, which suggests the improvement is related to benefits beyond faster oncology assessment.

Moving toward uniform and evidence-based practice of radiotherapy for management of cervical cancer in Ontario, Canada.

PURPOSE: To recognize the practice of radiotherapy for management of cervical cancer in Ontario, Canada, and to use the results of the survey to harmonize and standardize practice across the province. METHODS AND MATERIALS: An electronic survey (SurveyMonkey) was sent to all 14 provincial cancer centers by Cancer Care Ontario Gynecology Community of Practice (CoP) in 2013. The survey included 72 questions in four different categories: general/demographic, pretreatment assessment, external beam radiotherapy (EBRT), and brachytherapy (BT). RESULTS: Ten of 14 centers treated cervical cancer patients and had a dedicated BT suite. All 10 centers had a peer review process for quality assurance. EBRT technique was a 4-field box in eight of 10 centers. The dose/fractionation for pelvic EBRT was 45-50 Gy in 1.8-2 Gy/fraction in all but one center. Nine of 10 centers used high-dose-rate BT. Only one center offered interstitial BT. For treatment planning, two centers used CT and MRI, five centers used CT, and three centers used orthogonal x-rays. Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology guidelines were used in four of seven of the centers for target volume delineation and in five of seven centers for organs at risk dose constraints. All but one center prescribed and reported dose to Point A. CONCLUSIONS: The survey identified areas where practice varied across the province. Gynecology CoP used this information to identify priorities for practice change and implemented several strategies to harmonize the care of women with cervical cancer. This highlights the value of interdisciplinary, grass-roots initiatives such as CoPs to standardize practice in a practical manner that directly benefits patients.

Multidisciplinary Clinics in Lung Cancer Care: A Systematic Review.

Multidisciplinary cancer clinics (MDCCs) are recognized in cancer care as an alternate model of care for lung cancer patients. However, the precise MDCC characteristics that could potentially improve the quality of care in lung cancer care have not been clearly defined. We performed a systematic review of the data regarding MDCCs in the treatment of patients with lung cancer to summarize and evaluate the available evidence and to determine valuable clinic characteristics and projected outcomes. We searched Embase, Cochrane, Medline, PubMed, and Web of Science through April 2017 for studies that included ≥ 2 physician specialties in a MDCC for lung cancer. A total of 2374 unique articles were identified, of which 13 met the inclusion criteria. All the studies were either retrospective or qualitative, with many having small sample sizes. The most commonly reported quantitative outcome for MDCCs was a decreased time from diagnosis to treatment; however, this was only statistically significant in 2 studies. Evidence was conflicting regarding improved patient survival. Several studies of MDCCs reported improved qualitative outcomes, including increased patient satisfaction, increased collaboration, and cohesive communication among care providers, although the sample sizes were small. The few studies of MDCCs that included a care coordinator, in addition to physicians from multiple specialties, reported improvements in patient satisfaction. Overall, our review of the reported data revealed a paucity of evidence regarding the value of MDCCs for lung cancer patients, highlighting the need for further studies to understand the optimal medical model to deliver care.

Fractionation of Palliative Radiation Therapy for Bone Metastases in Ontario: Do Practice Guidelines Guide Practice?

PURPOSE: To evaluate the effect of a provincial practice guideline on the fractionation of palliative radiation therapy for bone metastases (PRT.B) in Ontario. METHODS AND MATERIALS: The present retrospective study used electronic treatment records linked to Ontario's population-based cancer registry. Hierarchical multivariable regression analysis was used to evaluate temporal trends in the use of single fractions (SFs), controlling for patient-related factors associated with the use of SFs. RESULTS: From 1984 to 2012, 43.9% of 161,835 courses of PRT.B were administered as SFs. The percentage of SF courses was greater for older patients (age <50 years, 39.8% vs age >80 years, 52.5%), those with a shorter life expectancy (survival >12 months, 36.9% vs < 1 month, 53.6%), and those who lived farther from a radiation therapy center (<10 km, 42.1% vs > 50 km, 47.3%). The percentage of SFs to spinal fields was lower than that to other skeletal sites (31.5% vs 57.1%). The percentage of SFs varied among the cancer centers (range, 26.0%-67.8%). These differences were all highly significant in the multivariable analysis (P<.0001). In 2004, Cancer Care Ontario released a practice guideline endorsing the use of SFs for uncomplicated bone metastases. The rate of use of SFs increased from 42.3% in the pre-guideline period (1999-2003) to 52.6% in the immediate post-guideline period (2004-2007). However, it subsequently decreased again to 44.0% (2009-2012). These temporal trends were significant after controlling for patient-related factors in the multivariable analysis (P<.0001). Large intercenter variations in the use of SFs persisted after publication of the guideline. CONCLUSIONS: The publication of an Ontario practice guideline endorsing the use of SF PRT.B was associated with only a transient increase in the use of SFs in Ontario and did little to reduce intercenter variations in fractionation.

An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer.

INTRODUCTION/BACKGROUND: An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC. MATERIALS AND METHODS: After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively). RESULTS: Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002), and adenocarcinoma histology (P = .036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%). CONCLUSION: Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment.

Is there an oligometastatic state in non-small cell lung cancer? A systematic review of the literature.

OBJECTIVES: Long-term survival has been observed in patients with oligometastatic non-small cell lung cancer (NSCLC) treated with locally ablative therapies to all sites of metastatic disease. We performed a systematic review of the evidence for the oligometastatic state in NSCLC. MATERIALS AND METHODS: A systematic review of MEDLINE, EMBASE and conference abstracts was undertaken to identify survival outcomes and prognostic factors for NSCLC patients with 1-5 metastases treated with surgical metastatectomy, Stereotactic Ablative Radiotherapy (SABR), or Stereotactic Radiosurgery (SRS), according to PRISMA guidelines. RESULTS: Forty-nine studies reporting on 2176 patients met eligibility criteria. The majority of patients (82%) had a controlled primary tumor and 60% of studies included patients with brain metastases only. Overall survival (OS) outcomes were heterogeneous: 1 year OS: 15-100%, 2 year OS: 18-90% and 5 year OS: 8.3-86%. The median OS range was 5.9-52 months (overall median 14.8 months; for patients with controlled primary, 19 months). The median time to any progression was 4.5-23.7 months (overall median 12 months). Highly significant prognostic factors on multivariable analyses were: definitive treatment of the primary tumor, N-stage and disease-free interval of at least 6-12 months. CONCLUSIONS: Survival outcomes for patients with oligometastatic NSCLC are highly variable, and half of patients progress within approximately 12 months; however, long-term survivors do exist. Definitive treatment of the primary lung tumor and low-burden thoracic tumors are strongly associated with improved long-term survival. The only randomized data to guide management of oligometastatic NSCLC pertains to patients with brain metastases. For other oligometastatic NSCLC patients, randomized trials are needed, and we propose that these prognostic factors be utilized to guide clinical decision making and design of clinical trials.

A population-based study of the fractionation of postlumpectomy breast radiation therapy.

PURPOSE: The optimal fractionation schedule of post lumpectomy radiation therapy remains controversial. The objective of this study was to describe the fractionation of post-lumpectomy radiation therapy (RT) in Ontario, before and after the seminal Ontario Clinical Oncology Group (OCOG) trial, which showed the equivalence of 16- and 25-fraction schedules. METHODS AND MATERIALS: This was a retrospective cohort study conducted by linking electronic treatment records to a population-based cancer registry. The study population included all patients who underwent lumpectomy for invasive breast cancer in Ontario, Canada, between 1984 and 2008. RESULTS: Over the study period, 41,747 breast cancer patients received post lumpectomy radiation therapy to the breast only. Both 16- and 25-fraction schedules were commonly used throughout the study period. In the early 1980s, shorter fractionation schedules were used in >80% of cases. Between 1985 and 1995, the proportion of patients treated with shorter fractionation decreased to 48%. After completion of the OCOG trial, shorter fractionation schemes were once again widely adopted across Ontario, and are currently used in about 71% of cases; however, large intercenter variations in fractionation persisted. CONCLUSIONS: The use of shorter schedules of post lumpectomy RT in Ontario increased after completion of the OCOG trial, but the trial had a less normative effect on practice than expected.