Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiotherapy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study.

BACKGROUND: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. MATERIALS/METHODS: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. RESULTS: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39-83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5-25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3-4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3-4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. CONCLUSION: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.

Prostate Cancer Metastasis to Stomach: A Case Report and Review of Literature.

Metastatic prostate cancer is a common diagnosis with a protracted but terminal course. Gastrointestinal (GI) tract involvement is extremely rare, and reportedly portends a poor prognosis. It can present years after the initial prostate cancer diagnosis. Only fifteen cases of prostate cancer metastasis to the stomach have been reported in the literature. We report a case of a 72-year-old man with metastatic castration-resistant prostate cancer and extensive bony involvement. He presented a decade after the diagnosis of prostate cancer with signs of heartburn; a gastric biopsy was initially believed to represent primary gastric carcinoma, but subsequently a diagnosis of prostate cancer metastatic to the stomach was confirmed. This case highlights the importance of the provision of a pertinent clinical history and clinical differential diagnosis at the time of submission of surgical pathology specimens, as well as highlighting the need to have a low index of suspicion to pursue additional pathologic markers whenever a presumed second adenocarcinoma is noted in the context of a patient having a history of current or prior advanced-stage adenocarcinoma of another site. The correct diagnosis can shield the patient from the morbidity of inappropriate surgical or medical management.

Impact of Pre-Treatment NLR and Other Hematologic Biomarkers on the Outcomes of Early-Stage Non-Small-Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

INTRODUCTION: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. RESULTS: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 109/L (IQR: 4.17-7.05 × 109/L). Median lymphocyte count was 1.63 × 109/L (IQR: 1.29-2.10 × 109/L), median monocyte count was 0.65 × 109/L (IQR: 0.54-0.83 × 109/L), median platelet count was 260.0 × 109/L (IQR: 211.0-302.0 × 109/L). The median NLR was 3.42 (IQR: 2.38-5.04), median MLR was 0.39 (IQR: 0.31-0.53), and median PLR was 156.4 (IQR: 117.2-197.5). On multivariable regression a higher NLR was associated with worse OS (p = 0.01; HR-1.26; 95% CI 1.04-1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS (p = 0.001; NLR^1 HR 0.36; 0.17-0.78; NLR^2 HR-1.16; 95% CI 1.06-1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. CONCLUSIONS: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.

Outcome of Locally Advanced Esophageal Cancer Patients Treated With Perioperative Chemotherapy and Chemoradiotherapy Followed by Surgery.

OBJECTIVES: Perioperative chemotherapy (P-CT) or neoadjuvant chemoradiation (C-RT) followed by surgical resection is the standard of care for locally advanced esophageal cancer (LAEC). We present an institutional review and outcome of patients with LAEC treated with neoadjuvant C-RT or P-CT followed by surgery. METHODS: Patients were identified through the Manitoba Cancer Registry. Overall survival (OS), recurrence-free survival (RFS), and time to recurrence (TTR) were compared using proportion hazard regression analysis. Metabolic and pathologic response rates were compared by the Fisher exact test. RESULTS: Sixty-seven patients were treated with C-RT and 32 with P-CT. Fifty-two percent of the patients had pretreatment and posttreatment positron emission tomography scans before surgery. Ninety-five percent of the patients in C-RT and 91% in P-CT had a partial metabolic response or stable disease. Sixty-one percent of C-RT and 34% of P-CT patients had tumor regression grade (TRG) 0 to 1; 39% of C-RT and 66% of P-CT had TRG 2 to 3 (P=0.018). Median OS was 37 and 18 months for patients with TRG 0 to 1 and 2 to 3, respectively (P=0.013, hazard ratio [HR]=1.96). Three-year OS was 43% versus 37% (P=0.37, HR=1.30), RFS was 34% versus 26% (P=0.87, HR=0.96), and median TTR was 30 versus 13 months (P=0.07, HR=0.59) for C-RT and P-CT, respectively. CONCLUSIONS: C-RT was associated with a higher degree of pathologically tumor regression. Patients with major tumor regression had a better outcome than those with minimal to poor response. There was a trend toward improved TTR with C-RT but no difference in OS or RFS.

Clinical Outcomes After Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancer: A Single Institutional Study.

Introduction The standard of care for early-stage non-small cell lung cancer (NSCLC) is surgery. However, for medical inoperable patients stereotactic body radiation therapy (SBRT) is an alternative method. The aim of the study is to assess the overall survival (OS), progression-free survival (PFS) and local control (LC) of patients diagnosed with NSCLC in Manitoba, Canada, between 2013 and 2017 and managed with SBRT. Materials and methods This retrospective study included a total of 158 patients (60.13% of the population were females) that were diagnosed with stage I-II NSCLC and were treated with lung SBRT between 2013 and 2017 in Manitoba. Demographics and clinical data were retrospectively extracted from the electronic patient record. Kaplan-Meier and Cumulative incidence curves were used to describe the OS, PFS, and LC outcomes. Results From the 158 patients, 32 patients were treated with 60 Gy in eight fractions, while 121 patients were treated with 48 Gy in four fractions. Only 85 patients had biopsy-proven NSCLC. The median OS was 2.87 years (95% confidence interval [CI] 2.16-3.43). OS rates at one and two years were 85% and 66%, respectively. The median PFS was 2.03 years (95% CI 1.65-2.77). Furthermore, one-year and two-year PFS rates were 77% and 51%, respectively. Only 10 patients progressed locally at one year and 17 at two years, making the LC rate 93% at the one-year and 87% at the two-year mark. Conclusion These findings add to a growing evidence base supporting SBRT in the treatment of clinically suspected and biopsy-proven early-stage NSCLC patients.

Population-based Assessment of Intermittent Androgen Deprivation Therapy Utilization for Relapsed, Nonmetastatic, Hormone-sensitive Adenocarcinoma of the Prostate.

OBJECTIVES: Androgen deprivation therapy (ADT) is the standard of care for men with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) after treatment failure. Although intermittent ADT (iADT) is noninferior to continuous ADT for prostate cancer outcomes, with superior quality of life and cost-to-benefit ratio, little is known regarding its real-world utilization. The authors aimed to determine the utilization of iADT in a Canadian Provincial Cancer Program for relapsed nmHSPC and identified risk factors associated with the nonreceipt of iADT. MATERIALS AND METHODS: This retrospective population-based cohort study used linked administrative databases to identify all patients with relapsed nmHSPC from 2012 to 2016 and quantified ADT prescription history. Patients were defined as iADT eligible if prostate-specific antigen (PSA) was <4 ng/mL and trending downwards on ≥2 sequential PSAs after ≥6 months of ADT. Univariable and multivariable logistic regression analyses were performed to determine factors associated with nonreceipt of iADT. RESULTS: A total of 601 men with relapsed, nmHSPC were included with a median age at relapse of 73 (range, 46 to 96), pre-ADT PSA of 12.2 ng/mL, and a median pre-ADT PSA doubling time of 7.8 months. 80.9% of the cohort were eligible to receive iADT and 74.4% were treated with iADT. On multivariable analysis, patients originally treated with surgery (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08-0.46) or having a Gleason Score ≥8 (OR, 0.30; 95% CI, 0.12-0.78) had decreased odds of receipt of iADT. Patients with longer PSA doubling times were more likely to receive iADT (OR, 2.71; 95% CI, 1.17-6.31). CONCLUSIONS: The utilization of iADT was relatively common for men in Manitoba during the study period, however, the uptake of iADT can be improved among identified subgroups.

Bracing for impact with new 4R's in the COVID-19 pandemic - A provincial thoracic radiation oncology consensus.

As COVID-19 pandemic continues to explode, cancer centers worldwide are trying to adapt and are struggling with this constantly changing scenario. Intending to ensure patient safety and deliver quality care, we sought consensus on the preferred thoracic radiation regimen in a Canadian province with 4 new R's of COVID era.

Role of thoracic consolidation radiation in extensive stage small cell lung cancer: A systematic review and meta-analysis of randomised controlled trials.

Extensive stage small cell lung cancer (ES-SCLC) carries a poor prognosis, and the thoracic progression is common. Consolidation radiation to thoracic disease (cRT) could improve progression-free survival (PFS) and overall survival (OS). We conducted an electronic search of PubMed and Embase with no language, year or publication status restrictions and evaluated randomised controlled trials (RCTs) addressing the role of cRT in ES-SCLC. Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines for systematic review and Cochrane methodology for meta-analysis were followed. Effect estimates (hazard ratios [HRs] and confidence intervals [CIs]) and risk ratios were extracted, with a fixed/random-effects model created to estimate treatment effects. I2 statistics and heterogeneity statistics were performed. Comprehensive and systematic search identified 1107 records, after removal of duplicate records screened 922 records, assessed 31 full-text articles for eligibility and 3 RCTs with a total of 690 patients were included. Pooled analysis showed cRT significant improved PFS (p < 0.0001) with HR 0.72 (95% CI: 0.61-0.83, I2-0%). In addition, cRT significantly (p < 0.001) reduced the risk of thoracic progression as the first site of progression with a relative risk of 0.52 (95% CI: 0.44-0.61, I2-0%). OS analysis showed no significant (p = 0.36) benefit with HR of 0.88 (95% CI 0.66-1.18, I2-52%) with cRT. Pooled meta-analysis of 3 randomised controlled studies shows consolidation thoracic radiotherapy (RT) offers significant improvement in PFS and reduction in thoracic failures. Further research on subclassification of ES-SCLC (limited vs extensive metastasis), optimise strategy for RT integration (sequential vs concurrent) and optimal RT dose is needed to identify the subset of ES-SCLC likely to have significant OS benefit.

Role of Stereotactic Body Radiation Therapy in Early Stage Small Cell Lung Cancer in the Era of Lung Cancer Screening: A Systematic Review.

With the obvious benefit from low dose computed tomography to reduce the lung cancer-specific mortality, lung cancer screening is on the rise. With the implementation of the screening programs, diagnosis of early stage lung cancer is expected to increase, and small cell lung cancer (SCLC) would account for 10% of screen-detected lung cancer. Apart from Concurrent chemoradiation (CRT), the present guidelines virtually do not support other options for radiation (RT). There is a paucity of data addressing the role of Stereotactic Body Radiation Therapy (SBRT) in SCLC and we conducted the current systematic review on this topic. We systematically searched literature using the electronic databases PubMed and Embase with no language, year or publication status restrictions. After removal of duplicate records, 3469 screened, 3446 excluded with reasons, 23 full-text articles were assessed for eligibility, and 7 studies (8 reports) were included. Unsuitability for surgery or refusal for surgery was the most common reason for the use of SBRT in early stage SCLC in the included studies. Variable patterns of SBRT-chemotherapy (CT) sequencing including concurrent, pre-CT and post-CT and radiation doses were noted. Within the reported studies overall survival (OS) at 1 year, 2 year and 3 year varied from 63% to 87%, 37% to 72%, and 35% to 72%, respectively. Distant metastasis was the most common pattern of failure ranging from 38% to 53%. There was no increase in the reported grade III toxicity. SBRT could be a potential option in stage I SCLC with comparable outcomes with no added toxicity. Acknowledging the limitations and absence of high-quality data, presently cautious interpretation is warranted and further studies are needed to establish the role of SBRT in SCLC.

Comparison of 7th and 8th editions of the UICC/AJCC TNM staging for non-small cell lung cancer in a non-metastatic North American cohort undergoing primary radiation treatment.

BACKGROUND: We compared the performance of 7th and 8th edition of the Union for International Cancer Control (UICC) / American Joint Committee on Cancer (AJCC) TNM staging for non-small cell lung cancer (NSCLC) in non-metastatic (stage I-III) North American cohort undergoing primary radiation treatment. METHODS: Newly diagnosed NSCLC between (Jan 2011 - Dec 2014) were screened through a Canadian Provincial Cancer Registry. Clinico-radiologically and pathologically confirmed non-metastatic NSCLC undergoing primary radiation treatment were included. Kaplan-Meier methods, Cox proportional hazard regression and Akaike information criterion (AIC) were applied to evaluate discriminatory ability and prognostic performance of 7th and 8th edition of staging systems. RESULTS: In this cohort of 295 patients, 8th edition stages IA3, IB, IIA, IIB, IIIA, IIIB, and IIIC showed progressive increase in the hazard ratio compared to best stage IA2 (8th edition IA3 vs IA2: HR 1.72; IB vs IA2: HR 2.04; IIA vs IA2: HR 2.66; IIB vs IA2: HR 2.91; IIIA vs IA2: HR 3.38; IIIB vs IA2: HR 3.62 and IIIC vs IA2: HR 8.22). In a multivariate model, 8th edition stage grouping had smaller AIC of 2342.08 compared to 7th edition 2349.55, confirming better performance. International Association for the Study of Lung Cancer (IASLC) map based nodal categorization N1, N2 and N3, showed good survival and hazard discrimination over stage N0 (1.39, 1.48 and 2.16 respectively). CONCLUSION: In an independent cohort of non-metastatic NSCLC undergoing primary radiation treatment, improved performance of 8th edition UICC/AJCC staging system over 7th edition was observed.

Clinical Characteristics and Prognosis of Primary Tracheal Cancer: A Single Institution Experience.

Background Primary tracheal cancers (PTCs) are rare and current evidence-based understanding is limited to retrospective reports and national databases. We present single institutional study of a historical cohort of PTC from Canadian provincial cancer registry database. Materials and Methods: After institutional research ethics board approval, all PTC patients diagnosed from 1980 to 2014 were identified through the Canadian provincial cancer registry. Demographic and tumor related factors were evaluated using descriptive statistics. Survival rates were estimated using the Kaplan-Meier method and cox hazard regression analyses were performed to identify predictors of disease-free survival (DFS) and overall survival (OS). Results: A total of 30 patients were included in the study. At presentation, 10 patients (33%) had only local disease, 14 patients (47%) had locoregional disease and the remaining 4 patients (13%) had distant metastasis. The majority of patients underwent primary radiation treatment. The overall survival rate was 30% at 2 years and 16% at 5 years. Patients receiving radical-intent therapy had better 2-year DFS and OS compared to patients managed with palliative radiotherapy and best supportive care (46%, 17% and 0%) (p=<0.001) and (50%, 23% and 0%) (p=<0.001), respectively. Radiotherapy resulted in a better 2-year OS and DFS (32% versus 14%) (p=<0.03) and (32% versus 0%) (p=<0.001), respectively. Conclusion: PTC is an uncommon neoplasm making the study of the disease technically and logistically challenging. Radical radiotherapy alone is curative option in inoperable PTC. Intent of treatment and radiotherapy were associated with superior survival outcomes.

Clinical Implementation of a Model-Based In Vivo Dose Verification System for Stereotactic Body Radiation Therapy-Volumetric Modulated Arc Therapy Treatments Using the Electronic Portal Imaging Device.

PURPOSE: To report findings from an in vivo dosimetry program implemented for all stereotactic body radiation therapy patients over a 31-month period and discuss the value and challenges of utilizing in vivo electronic portal imaging device (EPID) dosimetry clinically. METHODS AND MATERIALS: From December 2013 to July 2016, 117 stereotactic body radiation therapy-volumetric modulated arc therapy patients (100 lung, 15 spine, and 2 liver) underwent 602 EPID-based in vivo dose verification events. A developed model-based dose reconstruction algorithm calculates the 3-dimensional dose distribution to the patient by back-projecting the primary fluence measured by the EPID during treatment. The EPID frame-averaging was optimized in June 2015. For each treatment, a 3%/3-mm γ comparison between our EPID-derived dose and the Eclipse AcurosXB-predicted dose to the planning target volume (PTV) and the ≥20% isodose volume were performed. Alert levels were defined as γ pass rates <85% (lung and liver) and <80% (spine). Investigations were carried out for all fractions exceeding the alert level and were classified as follows: EPID-related, algorithmic, patient setup, anatomic change, or unknown/unidentified errors. RESULTS: The percentages of fractions exceeding the alert levels were 22.6% for lung before frame-average optimization and 8.0% for lung, 20.0% for spine, and 10.0% for liver after frame-average optimization. Overall, mean (± standard deviation) planning target volume γ pass rates were 90.7% ± 9.2%, 87.0% ± 9.3%, and 91.2% ± 3.4% for the lung, spine, and liver patients, respectively. CONCLUSIONS: Results from the clinical implementation of our model-based in vivo dose verification method using on-treatment EPID images is reported. The method is demonstrated to be valuable for routine clinical use for verifying delivered dose as well as for detecting errors.