Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2-4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.

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.

Adjuvant Chemotherapy and Radiotherapy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Clinical Practice Guideline.

Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy [CRT], and stereotactic body radiation therapy [SBRT]) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.

High-dose-rate brachytherapy for airway malignancy a single institution experience.

PURPOSE: To evaluate clinical outcomes of endobronchial malignancy treated using high-dose-rate endobronchial brachytherapy (HDREB). METHODS AND MATERIALS: A retrospective chart review was conducted for all patients treated with HDREB for malignant airway disease between 2010 and 2019 at a single institution. Most patients had a prescription of 14 Gy in two fractions given a week apart. The Wilcoxon signed rank test and paired samples t test were used to compare changes in mMRC dyspnea scale prior to and after brachytherapy at first followup appointment. Toxicity data were collected for dyspnea, hemoptysis, dysphagia, and cough. RESULTS: A total of 58 patients were identified. Most (84.5%) had primary lung cancer with advanced cancers, stage III or IV (86%). Eight were treated while admitted in the ICU. Previous external beam radiotherapy (EBRT) was received by 52%. An improvement in dyspnea was seen in 72%, with an mMRC dyspnoea scale score improvement of 1.13 points (p < 0.001). Most (22, 88%) had an improvement in hemoptysis and 18 out of 37 (48.6%) had an improvement in cough. Grade four to five events occurred in 8 (13%) at the median time of 2.5 months from brachytherapy. Twenty-two patients (38%) had complete obstruction of the airway treated. Median progression free survival was 6.5 months and median survival was 10 months. CONCLUSIONS: We report a significant symptomatic benefit among patients receiving brachytherapy with endobronchial malignancy, with rates of treatment related toxicities similar to prior studies. Our study identified new subgroups of patients, ICU patients & those with complete obstruction, who benefited from HDREB.

Palliative Radiotherapy for Esophageal and Gastric Cancer: Population-Based Patterns of Utilization and Outcomes in Ontario, Canada.

OBJECTIVE: Patients with incurable esophageal and gastric cancer may develop local symptoms for which palliative radiotherapy (PRT) may be considered. We sought to evaluate patterns in utilization and outcomes of patients receiving PRT for incurable esophageal and gastric cancer in Ontario, Canada using health administrative data. METHODS: Linked health administrative databases were used to identify patients receiving PRT for incurable esophageal and gastric cancer. Primary outcomes were utilization and delivery of PRT, utilization of endoscopic dilation with or without stent insertion after completion of PRT and survival from 1) date of diagnosis and 2) start of PRT. RESULTS: We identified 2500 patients who received PRT. Mean age was 70 ± 13 years and the majority (75%, n = 1873/2500) were male. Over half of the patients had a diagnosis of gastric cancer (58%, n = 1453/2500) and began PRT within 6 months of cancer diagnosis (85%, n = 2125/2500). Of the 2500 patients in the cohort, 2174 patients received EBRT with few receiving brachytherapy (n = 326) or EBRT and brachytherapy combined (n = 88). Over the study period, there was an increase in the number of patients receiving PRT (136 in 2007 to 290 in 2016), as well as in the use of advanced conformal radiotherapy techniques. Only 5% (115/2500) required dilation with or without stent insertion after completion of PRT. Median overall and cancer-specific survival of the cohort was 205 days and 209 days from date of diagnosis and 108 days and 110 days from start of PRT. CONCLUSIONS: PRT is an important treatment for patients with incurable esophageal and gastric cancer who present with local symptoms. Utilization of PRT and advanced EBRT techniques increased over the study period. Few patients require endoscopic dilation with or without stent insertion after completion of PRT suggesting that PRT provides favorable symptom control.

Adjuvant Radiotherapy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis.

PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present. METHODS AND MATERIALS: We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR). RESULTS: Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23-0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes. CONCLUSIONS: Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

Non-surgical management of advanced hepatocellular carcinoma: A systematic review by Cancer Care Ontario.

Background: Hepatocellular carcinoma (HCC) is a global health problem, accounting for 4.7% of all new cancer cases and 8.2% of all cancer deaths worldwide in 2018. Resection and transplantation are the only modalities that offer a cure for HCC; however, most patients are diagnosed at an advanced stage, precluding these curative treatments. A number of local (ie, ablative therapies) and/or local-regional therapies (ie, chemo-embolization) are used and followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy compared with these standards is not well known. Methods: Literature searches (1/2000 to 1/2020 or 1/2005 to 1/2020, depending on the specific systematic review question) were conducted, including MEDLINE, Embase and the Cochrane Database of Systematic Reviews. Results: Over 30,000 articles were identified. In total, 49 studies were included in the systematic review. Conclusions: There is no evidence to support the addition of sorafenib to any local or regional therapy. First-line systemic therapy options for unresectable or metastatic HCC include sorafenib, lenvatinib, and atezolizumab + bevacizumab. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment.

Outcomes of Multi-disciplinary Management of Metastatic Renal Cell Carcinoma.

Metastatic renal cell carcinoma (mRCC) is associated with a poor prognosis. It is traditionally a treatment-resistant disease necessitating multi-modal treatment and close follow-up. We herein report a case of mRCC in a patient who was managed closely by a multi-disciplinary team and still retained a very good performance status and treatment response three years after diagnosis. We highlight the importance of close monitoring, switching systemic therapies at progression, early palliative radiotherapy, and patient education in controlling disease burden and maintaining quality of life in patients with mRCC.

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.

Perioperative chemotherapy for urothelial carcinoma of the upper urinary tract: A systematic review and meta-analysis.

INTRODUCTION: Upper tract urothelial carcinomas are rare malignancies with differences in anatomy and biology requiring therapeutic strategies that differ from bladder cancer. The role of perioperative systemic therapy in this disease remains uncertain with limited data to support its use. A systematic review of the literature and meta-analysis was therefore undertaken to provide more information and guide clinical practice. METHODS: A literature search was performed using Embase and Medline databases with additional searches performed manually using terms associated with upper tract urothelial malignancies. Data was extracted from studies of patients that underwent nephrouretectomy for the management of upper tract urothelial carcinoma and received either neoadjuvant or adjuvant systemic therapy. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were summated and analyzed using Cochrane Revman software Version 5.3. RESULTS: There were 13 comparative studies and no randomized studies identified for data extraction; 11 adjuvant and 2 neoadjuvant with 1170 patients receiving perioperative systemic therapy and 3472 controls that did not. Perioperative chemotherapy was associated with improved OS (HR 0.75, 95%CI 0.57-0.99), DFS (HR 0.54, 95%CI 0.32-0.92), and CSS (HR 0.69, 95%CI 0.42-1.15). CONCLUSIONS: The available data suggests that perioperative systemic therapy is associated with improved survival in patients with upper tract urothelial cancer.

Validation of predictors for lymph node status in penile cancer: Results from a population-based cohort.

INTRODUCTION: The ability to predict lymph node (LN) status is essential in the management of men with localized squamous cell carcinoma (SCC) of the penis. There has been limited external validation of available risk stratification tools, particularly in routine clinical care. The objective of this study was to evaluate the predictive variables of LN metastases within a large population-based cohort of patients. METHODS: In this population-based cohort study, surgical pathology reports were linked to the population-based Ontario Cancer Registry to identify all patients who were diagnosed with penile cancer in Ontario, Canada. Multivariable analyses were performed to evaluate predictive variables for LN involvement. Three contemporary risk stratification schemes used to predict LN status were analyzed by logistic regression. RESULTS: The study included 380 localized penile SCC cases treated between 2000 and 2010. Sixty-three (17%) had pathologically confirmed LN metastases. Among these, 35 (56%) were diagnosed within three months of the initial penile SCC diagnosis and these patients had a worse five-year disease-specific survival (43%; 95% confidence interval [CI] 26-64) compared to patients who were diagnosed at a delayed LN dissection. On multivariable analysis, age (odds ratio [OR] 0.68; 95% CI 0.52-0.88), pathological stage (≥pT1b; OR 3.32; 95% CI 1.38-8.01), and tumour grade (Grade 2 OR 2.98; 95% CI 1.26-7.62; Grade 3 OR 3.97; 95% CI 1.32-11.9) were associated with an increased risk of LN metastases. Candidate risk stratification schemes demonstrated moderate to good property, with C-statistics ranging from 0.662-0.747. CONCLUSIONS: Using a population-based cohort of penile cancer patients with a relatively low proportion of patients with pathologically confirmed LN involvement, we confirm and externally validate the importance of age, stage, and grade of the primary tumour in predicting nodal status.

Patient Reported Outcomes After Radiation Therapy for Bone Metastases as a Function of Age: A Secondary Analysis of the NCIC CTG SC-Twenty-Three Randomized Trial.

PURPOSE: To explore the age difference in response and patient-reported outcomes in patients with cancer having bone metastases undergoing palliative radiotherapy. METHODS: Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life (QOL) Bone Metastases module (QLQ-BM22), EORTC QOL Core-15-Palliative (QLQ-C15-PAL), and Dexamethasone Symptom Questionnaire (DSQ) before a single 8-Gy radiation treatment, on days 10 and 42 after treatment. Patient demographics, performance status, analgesic consumption, BM22, C15, and DSQ were compared with multivariant analysis between patients under 75 years and 75 years and older. Multiple linear regression models were used to assess the differences between age-groups, adjusting for baseline demographics and primary disease sites. RESULTS: There were 298 patients (170 male) with 209 (70%) less than 75 years of age. Most common primary cancer sites include lung, prostate, and breast. At baseline, younger patients had better performance status, consumed more analgesic, and reported worse scores in nausea, insomnia, and functional interference, while older patients more commonly had prostate cancer. There were no significant differences in the incidence of radiation-induced pain flare; response to radiation; changes from baseline for BM22, C15-PAL; and DSQ, nor overall survival at day 42 between the 2 groups. Responders to radiation in the elderly group reported better improvement in physical and emotional domains when compared with nonresponders. CONCLUSIONS: In patients with cancer having bone metastases undergoing palliative radiotherapy, there was no significant difference in general with age in response to radiation and patient-reported outcomes. Palliative radiotherapy should be offered to elderly patients when needed.

Gender differences in pain and patient reported outcomes: a secondary analysis of the NCIC CTG SC. 23 randomized trial.

BACKGROUND: Gender differences may contribute to variations in disease presentations and health outcomes. To explore the gender difference in pain and patient reported outcomes in cancer patients with bone metastases undergoing palliative radiotherapy on the National Cancer Institute of Canada (NCIC) SC.23 randomized trial. METHODS: Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QOL) bone metastases module (QLQ-BM22) and EORTC QOL Core-15-Palliative (QLQ-C15-PAL) before treatment and at days 10 and 42 after a single 8 Gy radiation treatment. Patient demographics, performance status, analgesic consumption, BM22 and C15 were compared between males and females using the 2-sample t-test for continuous variables or the Chi-squared test for categorical variables. Multiple linear regression models were used to check the difference between gender groups adjusting for the baseline demographics and primary disease sites. RESULTS: There were 298 patients (170 male, 128 female) with median age of 69 years. The most common primary cancer sites were lung, prostate and breast. At baseline, there were no differences in BM22 and C15 scores, except a worse nausea and vomiting score (P=0.03) in females on the C15. In patients with moderate baseline worst pain scores (WPS), females reported worse scores in painful sites of BM22. At day 42, there was no significant difference in response to radiotherapy. Among the responders, females reported better improvement in emotional aspect. CONCLUSIONS: In cancer patients with bone metastases undergoing palliative radiotherapy, the majority of symptom presentations, patient reported outcomes, and response to radiation was not significantly different between genders. TRIAL REGISTRATION: NCT01248585.

PET imaging in anal canal cancer: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to systematically review the literature to synthesize and summarize the evidence surrounding the clinical utility of positron emission tomography (PET) imaging in patients with anal canal cancer. METHODS: The literature was searched using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews databases. Studies comparing PET or PET/CT with conventional imaging in the staging, response evaluation and follow-up of anal canal cancer were deemed eligible for inclusion. RESULTS: 17 studies met the inclusion criteria. For the detection of primary tumour in situ, the pooled sensitivity was 99% for PET or PET/CT and 67% for CT. For the detection of inguinal lymph nodes, PET/CT had an overall sensitivity of 93% and specificity of 76%. PET or PET/CT upstaged 5.1 to 37.5% of patients and downstaged 8.2 to 26.7% of patients. Treatment plans were modified in 12.5 to 59.3% of patients, which consisted mainly of radiotherapy dose or field changes. Complete response on PET or PET/CT is a good prognostic factor for overall and progression-free survival. CONCLUSIONS: PET/CT seems to add value to conventional imaging in the initial staging of patients with T2-4 disease but further high-quality research is required to validate this. There is insufficient evidence at this time to recommend a routine use of PET/CT in the assessment of treatment response or follow-up. Advances in knowledge: PET/CT appears to alter the disease stage and management in a meaningful number of patients to justify its use as part of staging investigations in locally advanced cases.

Issues in Managing Hurthle Cell Carcinoma of Thyroid: A Case Report.

A 61-year-old woman noticed a right neck lump in October 2001. Fine needle aspiration showed follicular neoplasm, adenoma versus carcinoma. The ultrasound scan showed a solid mass of maximum dimension of 3.7 cm. She had a right thyroid lobectomy and isthmectomy in January 2002 (first surgery). The tissue specimen showed a 4.5 cm Hurthle cell carcinoma (HCC) with vascular invasion. There were no capsular invasion, extra-thyroidal extension, or margin involvement. A completion left lobectomy (second surgery) was performed two weeks later. Therefore the pathological stage is II (T3N0M0). She received adjuvant radioactive iodine ablation for residual thyroid tissue. By 2003, she developed local recurrence, which was resected (third surgery), followed by adjuvant external beam radiotherapy. Unfortunately, she developed further recurrence in the left main bronchus, as identified by Indium-111 Octreotide (Curium, Missouri, USA) and positron emission tomography-computed tomography PET-CT imaging in 2006. She underwent a left pneumonectomy (fourth surgery) in July 2006. In November 2007 she was found to have mediastinal recurrence which was treated with high-dose external beam radiotherapy. She initially responded but developed more local recurrence and a lung metastasis by 2011. She was treated with brivanib with ixabepilone, under a phase I clinical trial with mixed response. Her treatment was discontinued secondary to toxicity and she succumbed to her disease in 2012. This case report illustrates the natural history and clinical decision making for patients diagnosed with HCC of the thyroid. Specifically, we highlight the clinical issues surrounding the histopathological diagnosis, extent of surgical resection, radioiodine diagnostic imaging/ablative treatment, as well as external beam radiotherapy.

Effect of Radiotherapy on Painful Bone Metastases: A Secondary Analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23.

IMPORTANCE: Many studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown. OBJECTIVE: To investigate QOL at days 10 and 42 after radiotherapy with a bone metastases-specific QOL tool. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10). INTERVENTIONS: Patients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases. MAIN OUTCOMES AND MEASURES: Patients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points. RESULTS: A total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and psychosocial aspects (mean increase, 1.2 points in responders vs mean decrease of 2.2 points in nonresponders, P = .04). Comparing changes in QOL from baseline to day 42, responders had significantly greater improvements in the physical (mean increase, 6.2 vs -9.0; P < .001), emotional (mean increase, 12.3 vs -5.5; P < .001), and global domains (mean increase, 10.3 vs -4.5; P < .001) of the QLQ-C15-PAL compared with nonresponders. CONCLUSIONS AND RELEVANCE: Forty percent of patients experienced pain reduction and better QOL at day 10 after radiotherapy with further improvements in QOL at day 42 in responders. A single 8-Gy radiotherapy dose for bone metastases should be offered to all patients, even those with poor survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248585.

Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22.

PURPOSE: Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes. METHODS: We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA). RESULTS: The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1-5, 6, and 7-10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain. CONCLUSION: Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1-5 as mild pain, 6 as moderate pain, and 7-10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.