Shahida Ahmed

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

Early Stage W.H.O. Grade I and II Follicular Lymphoma Treated with Radiation Therapy Alone

Objectives This retrospective study was undertaken to evaluate the outcome of patients with stage I or II (limited stage), grade I–II follicular non-Hodgkin’s lymphoma (FL) treated with radiation therapy (RT) alone as initial management. Methods Patients with stage I or II and pathologically confirmed WHO grade I or II FL treated initially with RT alone between 1982 and 2008 were identified from a population based cancer registry. Results Forty patients with a mean age 61.3 years at diagnosis were identified. The median follow up was 6.9 years from the end of radiation therapy. Stage was I (n = 26) and II (n = 14). None had B symptoms. The Follicular Lymphoma International Prognostic Index (FLIPI) was low risk in 26 patients and intermediate risk in 5. Doses ranged from 15 Gy to 48 Gy, with a median dose of 35 Gy. All patients achieved a complete clinical response (CR). 5 and 10 year overall survival (OS) was 86% and 59%, progression free survival (PFS) 67% and 54%. Age ≥60 at diagnosis was associated with reduced OS, p = 0.029, but did not affect PFS. No other clinical features including grade or FLIPI were significant for outcomes. Local failure was uncommon occurring in 8% (3/40) although this was 21% (3/14) of all recurrences. Conclusions OS and PFS outcomes for radiation alone in limited stage low grade FL patients from this single institution study are consistent with previously published data. No predictors were prognostic for PFS. A dose of ≤35 Gy may be appropriate. In this highly selected homogeneous group the FLIPI loses discriminating ability. Local control is excellent, and a majority of patients are free of disease after 5 years.

Geographical disparities of rectal cancer local recurrence and outcomes: a population-based analysis.

BACKGROUND: Challenges exist in providing high-quality cancer treatments to populations spread over large geographical areas. Local recurrence of rectal cancer is a complicated clinical problem associated with high morbidity and mortality. OBJECTIVES: The objectives of this study were to evaluate population-based rates and predictors of local recurrence of rectal cancer in the Province of Manitoba, Canada, with emphasis on the effects of geography. DESIGN: This was a population-based retrospective analysis. Administrative data from the Manitoba Cancer Registry and individual patient charts were reviewed. SETTINGS: Patients with stages I to III rectal cancer who underwent surgery with curative intent in Manitoba between 2004 and 2006 were included. MAIN OUTCOME MEASURES: The primary outcome was the development of local recurrence after surgical resection. RESULTS: Three hundred seventy patients with a mean age of 67 years were identified. The 5-year local recurrence rate was 17.4%. In multivariate analysis, relative to Winnipeg residents, rural residents, regardless of where they underwent surgery, had an increased risk of local recurrence (HR, 3.47; 95% CI, 1.74–6.92 for surgery in Winnipeg; HR, 2.98; 95% CI, 1.59–5.57 for surgery in rural Manitoba). The absence of both neoadjuvant radiotherapy and adjuvant chemotherapy was associated with a higher risk of local recurrence. Higher risk of mortality was noted for rural patients (HR, 1.90; 95% CI, 1.24–2.89) and for those who developed local recurrence (HR, 2.01; 95% CI, 1.27–3.19). CONCLUSION: Local recurrence rates for rectal cancer are high in Manitoba. Geography is an important variable, because rural status is associated with higher local recurrence rates and decreased survival. The use of neoadjuvant radiotherapy was an important predictor of lower local recurrence rates. Further initiatives are imperative to identify why rural patients experience differences in outcomes in Manitoba.

Small Cell Cancer of the Bladder and Prostate: A Retrospective Review from a Tertiary Cancer Center

Background: Genitourinary small cell cancer (GUSCC) is a rare malignancy. Most of the published data on how to manage this malignancy is based on institutional experience. We undertook the current retrospective review to determine the outcome of the patients with GUSCC treated at CancerCare Manitoba, Canada over a period of 18 years. Methods: The Manitoba Cancer Registry was used to identify patients with a confirmed pathological diagnosis of small cell cancer (SCC) of the bladder or prostate between January 1, 1995, and October 31, 2013. Results: There were 42 patients identified, 28 bladder SCC (17 limited, 11 extensive stage) and 14 prostate SCC (one limited, 12 extensive, and one unknown stage). The median age was 70.7 years. There were 22 patients who were treated with chemotherapy and radiation, five received radiation only, four received chemo only, nine did not receive any treatment, one patient had surgery only, and one had surgery and radiation. The median and one-year overall survival for all patients was 10.7 months and 43%. The median and one-year overall survival of SCC of the bladder was 55.1 months and 71% for the limited stage and 10.1 months and 36% for the extensive stage. The median and one-year overall survival for extensive stage SCC of the prostate was 4.1 months and 17%. There was only one patient with limited stage SCC of the prostate who did not receive any treatment and died of progressive disease 11 months from diagnosis. Conclusions: Our findings suggest that patients with limited stage SCC of the bladder can have a surprisingly good outcome with multimodality treatment. The outcome of the patients with extensive stage SCC of the bladder and prostate remains dismal and optimal therapeutic options have yet to be determined.

How, When and Where to Discuss Do Not Resuscitate: A Prospective Study to Compare the Perceptions and Preferences of Patients, Caregivers, and Health Care Providers in a Multidisciplinary Lung Cancer Clinic

Background: Do Not Resuscitate (DNR) is a significant but challenging part of end-of-life discussions when dealing with incurable lung cancer patients. We have explored the perceptions and preferences of patients, their caregivers (CGs), and health care providers (HCPs) and the current practice and opinions on DNR discussions in a multidisciplinary lung cancer clinic. Materials and Methods: This is a prospective descriptive study with a mixed quantitative and qualitative methodology to capture perceptions of the participants. To obtain a rich description of participant responses to questionnaire items, we employed a ‘think aloud’ process that prompted participants to immediately verbalize their thoughts when responding to questionnaire items. We used content analysis and constant comparison techniques to identify, code and categorize primary themes in the captured data. Results: Ten patients with advanced-stage lung cancer; nine CGs from the lung clinic and ten HCPs from the Thoracic Disease Site Group (DSG) were enrolled in the study. Most patients had only a limited understanding of DNR. Most CGs had a fair to good understanding of DNR. Most HCPs perceived their patients to have understood DNR most of the time. When patients were interviewed, a theme of “anticipated discussion” about DNR was identified. Patients and CGs expressed having faith in the system and responsible physicians as to when to discuss DNR. HCPs embraced a clinician preference-based decision-making approach to engaging in DNR discussions. They desired more resources, more knowledge, more structure and more time to discuss DNR. Most HCPs felt that it would be worth conducting a prospective clinical trial to determine the best time to discuss DNR. Conclusions: This pilot study provides a unique mixed quantitative and qualitative understanding of the perceptions of patients with lung cancer and their CGs and HCPs regarding DNR discussion. Our findings will help further the development of evidence-based guidelines and a broad prospective study that would have important implications for policies and practices around DNR discussions in order to reduce the emotional pain of dying patients, their CGs and HCPs.

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

PurposePrevious 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.MethodsWe 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).ResultsThe 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.ConclusionOur 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.

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.

Targeting the Tumor: Assessing the Impact of Bladder Volume and Position on Accuracy of Radiation Delivery for Patients with Bladder Cancer

Context Daily variations in bladder size and position can negatively impact the ability to accurately deliver radiation. Aims We attempted to quantify how bladder volumes and positions change over the course of radiotherapy for muscle invasive bladder cancer and the planning target volume (PTV) margins required to account for such changes. Methods and material Cone-beam computed tomography (CT) images of 28 patients during their first, second, and third fractions and weekly thereafter were acquired. Bladders were contoured and the volume, centre of mass, and the maximal positions were recorded and compared to the planning CT scan. Statistical analysis Bladder parameters were analysed using regression analysis examining for time trends and correlation to the patient, tumour, or treatment-related factors. Results There was great variability in the mean bladder volumes during the radiotherapy courses (154.17 +/- 129.38 cm3). There were no statistically significant trends for volume changes. Deviations in bladder positions were seen but were small in magnitude. No patient factors were identified which could help predict bladder changes clinically. Bladder variability resulted in a high percentage of fractions (39.6%) in which part of the bladder was outside the PTV. Calculated PTV margins (for 90% of the population to receive 95% of the prescription dose) were 1.48 cm right, 1.15 cm left, 2.13 cm posterior, 1.52 cm anterior, 2.23 cm superior, and 0.52 cm inferior. Conclusions Because of random bladder changes, a significant number of fractions were treated in which the clinical target volume (CTV) fell outside of the PTV. Methods to minimize the amount of CTV that is missed on a fraction to fraction basis should be explored.

Prophylactic dexamethasone for radiation-induced bone-pain flare – Authors' reply

Sunnybook Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada (EC, CD); Juravinski Hospital and Cancer Centre, and McMaster University, Hamilton, ON, Canada (RMM); NCIC Clinical Trials Group, Cancer Research Institute, Queen’s University, Kingston, ON, Canada (KD, CFW); Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada (AN); Hopital Maisonneuve-Rosemont, Montreal, QC, Canada (PC); Centre Hospitalier de L’Université de Montréal, Montreal, QC, Canada (PW); CancerCare Manitoba, Winnipeg, MB, Canada (SA); Grand River Regional Cancer Centre, Grand River Hospital, Kitchener, ON, Canada (JK); London Regional Cancer Program, London, ON, Canada (ARD); Cancer Centre of Southeastern Ontario, Kingston General Hospital, Kingston, ON, Canada (AM); Cross Cancer Institute, Edmonton, AB, Canada (AF); Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (JSYW); Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada (KD); Queen’s University, Kingston, ON, Canada (MB); and Princess Margaret Hospital, Radiation Medicine Program, Ontario Cancer Institute, University of Toronto, Toronto, ON, Canada (RKSW)

Perceptions and Preferences of Patients with Terminal Lung Cancer and Family Caregivers about DNR

Background: Patients with terminal lung cancer and their families are challenged and stressed with the end of life discussions. Do Not Resuscitate (DNR) orders are a critical part of such discussions. Objective: To understand the perceptions and preferences of patients with terminal lung cancer and their family caregivers around DNR discussions. . Methods: Our quantitative component consisted of a pen-and-paper questionnaire that was followed by a ‘think aloud’ process to capture perceptions of participants in response to questionnaire items. Qualitative methods included content analysis and constant comparison techniques to identify, code, and categorize primary themes arising from ‘think aloud’ responses. Results: In this pilot study, 10 patients with advanced stage lung cancer and nine family caregivers were enrolled from one tertiary cancer care centre. Three major themes and several sub-themes were identified reflecting participants’ psychosocial environment, emotional responses to DNR discussions, and suggestions to improve DNR discussions. Most of the time, both patients and caregivers perceived a supportive environment within their family unit. Some patients were uncertain about their disease extent but most had entertained thoughts about prognosis and DNR status prior to having a discussion with their physician. A range of situations stimulated the DNR discussion. Most patients were uncertain about identifying the most appropriate health care provider (HCP) for DNR discussion. While participants found DNR discussions distressing, patients maintained hope in the face of accepting a terminal diagnosis. There were mixed feelings about the reversibility of a DNR decision and concerns about the care of the patients after being stated as DNR. Participants desired their HCP to be emotionally sensitive, knowledgeable, respectful, and straightforward. Conclusions: Most participants were open about their experiences with psychosocial supports and emotional reactions and made suggestions to HCP to improve DNR discussions. Further examination in larger longitudinal studies is required to validate the observations in the current study.