Kristin Harris

Palliative Radiotherapy Trials for Bone Metastases: A Systematic Review

PURPOSE The objective is to update previous meta-analyses with a systematic review of randomized palliative radiotherapy (RT) trials comparing single fractions (SFs) versus multiple fractions (MFs). METHODS The analysis includes all published reports from randomized trials comparing SF or MF schedules for the treatment of painful bone metastases with localized RT. A systematic review was performed using the random-effects model with Review Manager version 4.1 (Cochrane Collaboration, Oxford, UK). The odds ratio and 95% CI were calculated for each trial and presented in a forest plot. RESULTS A total of 16 randomized trials from 1986 onward were identified. For intention-to-treat patients, the overall response (OR) rates for pain were similar for SF at 1,468 (58%) of 2,513 patients and MF RT at 1,466 (59%) of 2,487 patients. The complete response (CR) rates for pain were 23% (545 of 2,375 patients) for SF and 24% (558 of 2,351 patients) for MF RT. No significant differences were found in response rates. Trends showing an increased risk for SF RT arm patients in terms of pathological fractures and spinal cord compressions were observed, but neither were statistically significant (P = .75 and P = .13, respectively). The likelihood of re-treatment was 2.5-fold higher (95% CI, 1.76 to 3.56) in SF RT arm patients (P < .00001). Repeated analysis of these end points, excluding dropout patients, did not alter the conclusions. Generally, no significant differences with respect to acute toxicities were observed between the arms. CONCLUSION No significant differences in the arms were observed for overall and CR rates in both intention-to-treat and assessable patients. However, a significantly higher re-treatment rate with SFs was evident.

Palliative Thoracic Radiotherapy for Lung Cancer: A Systematic Review

PURPOSE The optimal dose of radiotherapy (RT) to palliate symptomatic advanced lung cancer is unclear. We systematically reviewed randomized controlled trials (RCTs) of palliative thoracic RT. METHODS RCTs comparing two or more dose fractionation schedules were reviewed using the random-effects model of a freely available information management system. The relative risk and 95% CI for each outcome were presented in Forrest plots. Exploratory analysis comparing dose schedules after conversion to the time-adjusted biologically equivalent dose (BED) was performed to investigate for a dose-response relationship. RESULTS A total of 13 RCTs involving 3,473 randomly assigned patients were identified. Outcomes included symptom palliation, overall survival, toxicity, and reirradiation rate. For symptom control in assessable patients, lower-dose (LD) RT was comparable with higher-dose (HD), except for the total symptom score (TSS): 65.4% of LD and 77.1% of HD patients had improved TSS (P = .003). Greater likelihood of symptom improvement was seen with schedules of 35 Gy(10) versus lower BED. At 1 year after HD and LD RT, 26.5% versus 21.7% of patients were alive, respectively (P = .002). Sensitivity analysis suggests this survival improvement was seen with 35 Gy(10) BED schedules compared with LDs. Physician-assessed dysphagia was significantly greater in the HD arm (20.5% v 14.9%; P = .01), and the likelihood of reirradiation was 1.2-fold higher after LD RT. CONCLUSION No significant differences were observed for specific symptom-control end points, although improvement in survival favored HD RT. Consideration of palliative thoracic RT of at least 35 Gy(10) BED may therefore be warranted, but must be weighed against increased toxicity and greater time investment.

Predictive Model for Survival in Patients With Advanced Cancer

PURPOSE To derive and validate a simple predictive model for survival of patients with metastatic cancer attending a palliative radiotherapy clinic. PATIENTS AND METHODS We described previously a model predicting survival of patients referred for palliative radiotherapy using six prognostic factors: primary cancer site, site of metastases, Karnofsky performance score (KPS), and the fatigue, appetite, and shortness of breath subscales from the Edmonton Symptom Assessment Scale. Here we simplified the model to include only three factors: primary cancer site, site of metastases, and KPS. Each factor was assigned a value proportional to its prognostic weight, and the weighted scores for each patient were summed to obtain a survival prediction score (SPS). Patients were also grouped according to their number of risk factors (NRF): nonbreast cancer, metastases other than bone, and KPS < or = 60. The three- and six- variable models were evaluated for their ability to predict survival in patients referred during a different time period and of those referred to a different cancer center. RESULTS A training set of 395 patients, a temporal validation set of 445 patients, and an external validation set of 467 patients were used. The ability of the three- and six-variable models to separate patients into three prognostic groups and to predict their survival was similar using both SPS and NRF methods in the training, temporal, and external validation data sets. There was no statistically significant difference in the performance of the models. CONCLUSION The three-variable NRF model is preferred because of its relative simplicity.

Validation of a Predictive Model for Survival in Metastatic Cancer Patients Attending an Outpatient Palliative Radiotherapy Clinic

PURPOSE To validate a predictive model for survival of patients attending a palliative radiotherapy clinic. METHODS AND MATERIALS We described previously a model that had good predictive value for survival of patients referred during 1999 (1). The six prognostic factors (primary cancer site, site of metastases, Karnofsky performance score, and the fatigue, appetite and shortness-of-breath items from the Edmonton Symptom Assessment Scale) identified in this training set were extracted from the prospective database for the year 2000. We generated a partial score whereby each prognostic factor was assigned a value proportional to its prognostic weight. The sum of the partial scores for each patient was used to construct a survival prediction score (SPS). Patients were also grouped according to the number of these risk factors (NRF) that they possessed. The probability of survival at 3, 6, and 12 months was generated. The models were evaluated for their ability to predict survival in this validation set with appropriate statistical tests. RESULTS The median survival and survival probabilities of the training and validation sets were similar when separated into three groups using both SPS and NRF methods. There was no statistical difference in the performance of the SPS and NRF methods in survival prediction. CONCLUSION Both the SPS and NRF models for predicting survival in patients referred for palliative radiotherapy have been validated. The NRF model is preferred because it is simpler and avoids the need to remember the weightings among the prognostic factors.

RECURSIVE PARTITIONING ANALYSIS OF PROGNOSTIC FACTORS FOR SURVIVAL IN PATIENTS WITH ADVANCED CANCER

PURPOSE To construct a predictive model for survival of patients referred to the Rapid Response Radiotherapy Program using recursive partitioning (RP). METHODS AND MATERIALS We analyzed 16 factors characterizing patients with metastases at first referral to the Rapid Response Radiotherapy Program for palliative radiotherapy in 1999 for their effect on survival. They included age, primary cancer site, site of metastases, weight loss (>or=10% during the past 6 months), Karnofsky performance status (KPS), interval from the first diagnosis of cancer to the first consultation at the Rapid Response Radiotherapy Program, analgesic consumption within the previous 24 h, and the nine symptom scores from the Edmonton Symptom Assessment Scale. We used RP to develop a predictive model of survival for patients referred in 1999, followed by temporal validation using patients referred in 2000, and external validation using patients referred in 2002 to another institution. RESULTS The model was able to separate patients into three groups with different durations of survival that were defined by (1) KPS >60; (2) KPS <or=60 with bone metastases only; and (3) KPS <or=60 with other metastases. The model performed moderately well when applied to the validation sets, but a major limitation was that it led to an unequal distribution of patients, with a small proportion of patients in the intermediate group. CONCLUSION We have demonstrated that RP can be used to predict the survival of patients with advanced cancer. However, this model has no advantages compared with our published prognostic models that use the survival prediction scores and number of risk factors.

Quality of life measurement in bone metastases: A literature review

Quality of life (QOL) has become an important consideration in the care of patients with bone metastases as prevalence, incidence and patient survival are on the rise. As a result, more interventional studies now measure patient’s QOL as a meaningful endpoint. However, well-developed bone metastases specific quality of life instruments are lacking. A literature review was conducted to better understand the nature of QOL instruments used in bone metastases trials. A total of 47 articles evaluating QOL in patients with bone metastases were identified. Twenty-five different instruments were used to evaluate QOL with study-designed questionnaires and the EORTC QLQ-C30 being most commonly employed. Many studies used more than one scale or instrument to measure QOL. This makes it difficult to compare QOL in bone metastases patients across studies and come to any formal conclusions. Therefore, this review demonstrates the need to develop a bone module that can be used across countries in future clinical trials.

Involvement of Family Physicians in the Care of Cancer Patients Seen in the Palliative Rapid Response Radiotherapy Program

PURPOSE It is important for cancer patients to maintain continuity of care with their family physician (FP) while being followed at the cancer center. The primary objective of this study was to determine the perception of patients seen in the palliative Rapid Response Radiotherapy Program (RRRP) on FP involvement in their cancer care. Secondary objectives were to identify factors predicting for perceived FP involvement in patient cancer care. PATIENTS AND METHODS Consecutive patients were approached for study enrollment at the time of RRRP visit and asked to complete a 15-item survey. RESULTS Three hundred sixty-five patients were accrued over 15 months. Ninety-eight percent had an FP, and 43% felt their FP was involved in their cancer care. Eighty percent of patients were satisfied with the overall medical care provided by their FP, and 71% had been with their FP for > or = 5 years. The most common reason patients gave for perceiving limited FP involvement was the medical oncologist looking after all of their cancer needs. Multivariate analysis found that satisfaction with overall medical care provided by the FP, shorter time since last FP visit, seeing the FP since cancer diagnosis, and FP providing on-call service for after-hour emergencies all significantly predicted for patients perceiving FP involvement in their cancer care. CONCLUSION Less than half of patients surveyed perceived their FP as involved in their cancer care. Encouraging continuity of care between patients and FPs may allow for easier transition of care back to the FP once palliative treatment at the cancer center has finished and help facilitate end-of-life planning.

A multidisciplinary bone metastases clinic at Toronto Sunnybrook Regional Cancer Centre – A review of the experience from 1999 to 2005

Our objective in this study was to review the experience of a one-stop multidisciplinary bone metastases clinic (BMC) that offers a coordinated multidisciplinary approach to the care of cancer patients with bone metastases in a tertiary cancer centre. Patients with symptomatic bone metastases were referred to BMC and assessed by a team of specialists in various disciplines - interventional radiology, orthopedic surgery, palliative medicine, and radiation oncology. At initial consultation, patient demographics, reasons for referral, and case disposition were recorded. From January 1999 to February 2005, a total of 272 patients with bone metastases were referred to the BMC. The median age was 65 years (range 28-95) and median KPS score at consultation was 60 (range 30-90). The majority of patients came from home (74%), while others came from a nursing home or the hospital (9%). Almost a third (28%) of patients had 2 or more reasons of referral, yielding a total of 354 reasons. The most common reason for referral was bone pain (42%), bone metastases (21%), high risk for pathological fracture (12%), and pathological fracture (10%). Of the 272 patients who received consultation, 40% received palliative radiotherapy, 19% received interventional surgery, 7% were referred to other support services such as palliative care, physiotherapy, and 7% had further investigation or imaging. A multidisciplinary clinic is useful for co-coordinating the management of bone metastatic disease in symptomatic patients.