Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS).

INTRODUCTION: Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. METHODS: Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. RESULTS: 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35 Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24 Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5 cc and 37.5 Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). CONCLUSION: Salvage HSRS results in high local control rates and toxicity rates that compare favorably to those single fraction SRS re-irradiation experiences reported in the literature.

Gamma knife icon based hypofractionated stereotactic radiosurgery (GKI-HSRS) for brain metastases: impact of dose and volume.

OBJECTIVE: Gamma Knife Icon-based hypofractionated stereotactic radiosurgery (GKI-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the GKI stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control and adverse radiation effect (ARE) outcomes following 5 fraction GKI-HSRS for intact brain metastases. METHODS: Patients with intact brain metastases treated with 5-fraction GKI-HSRS were retrospectively reviewed. Survival, local control, and adverse radiation effect rates were determined. Univariable and multivariable regression (MVA) were performed on potential predictive factors. RESULTS: Two hundred and ninety-nine metastases in 146 patients were identified. The median clinical follow-up was 10.7 months (range 0.5-47.6). The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5) in 5 daily fractions and 52% (range, 45-93), respectively. The median overall survival (OS) was 12.7 months, and the 1-year local failure rate was 15.2%. MVA identified a total dose of 27.5 Gy vs. ≤ 25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥ 4.5 cc (HR 7.29, p < 0.001) as a significant predictor of symptomatic ARE. CONCLUSION: Moderate total doses in 5 daily fractions of GKI-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE.

Fatigue scores in patients receiving palliative radiotherapy for painful bone metastases.

INTRODUCTION: The purpose of this study was to examine changes in fatigue scores for patients receiving radiation therapy for bone metastases and its impact on quality of life (QOL). METHODS: Fatigue and QOL scores were prospectively collected in patients for up to 3 months following radiation therapy for bone metastases using three questionnaires: group 1, Edmonton Symptom Assessment System (ESAS) (0-10); group 2, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30); and Core 15 Palliative (EORTC QLQ-C15-PAL) (1-4). RESULTS: Average fatigue score in group 1 (399 patients) was 4.72 at baseline, 5.08 at month 1, 5.01 at month 2, and 4.95 at month 3, and was 2.40, 2.39, 2.56, and 2.70 in group 2 (482 patients), respectively. Thirty-five percent of patients in group 1 had fatigue score increase ≥2 points at month 1, 36% at month 2, and 36% at month 3. Twenty-one percent of patients in group 2 had fatigue score increase ≥1 at month 1, 27% at month 2, and 40% at month 3. There was a statistically significant increase in fatigue score from baseline to all 3 months in group 1 only. In both groups, there was a highly significant negative correlation between fatigue and overall QOL scores at baseline and any follow-up month. CONCLUSIONS: There was a statistically significant worsening in fatigue in group 1 only. Up to one third had increased fatigue of clinical significance. Patients with less fatigue symptoms reported better overall QOL.

Student Accomplishments in the Rapid Response Radiotherapy Program: A 10-Year Review.

In 1996, the Toronto Sunnybrook Regional Cancer Centre developed the Rapid Response Radiotherapy Program (RRRP). The objective of this clinic is to consult, simulate, plan, and treat patients with palliative radiotherapy on the same day. In 2004, the RRRP initiated a program to provide clinical and research experience to undergraduate students interested in health sciences. The purpose of this study is to review the 10-year (2004-2013) experience of the RRRP and to examine whether the goals of the student program have been met. Students who worked in the RRRP from 2004 to 2013 were contacted to complete a short survey regarding their overall experience with the program and their current endeavors. Student accomplishments were collected from an internal database as well as PubMed. Descriptive statistics were used to analyze results. A total of 54 students from ten postsecondary institutions have worked in the RRRP; 29 were from the University of Waterloo undergraduate co-op program. In total, 214 articles with first authorship from students were published, 93 (43%) of which can be found on PubMed. Other accomplishments include 40 book chapters, 58 invited presentations, and 99 awards cumulatively. Qualitative data regarding student perspectives of their experience in the RRRP were also analyzed. Over the past 10 years, the RRRP has achieved its goal of providing quality medical and research experience to students interested in the health sciences. Using the responses of past and present students, we hope to continue to shape our program and provide unique opportunities to future students.

Fatigue scores in patients with brain metastases receiving whole brain radiotherapy.

PURPOSE: Whole brain radiotherapy (WBRT) is a treatment strategy used commonly to relieve burdensome symptoms and improve quality of life (QOL) in patients with multiple brain metastases. The purpose of this study is to determine changes in fatigue score following WBRT as it is a common symptom experienced in this population. METHODS: Fatigue and overall QOL scores were collected prospectively in patients for up to 3 months post-WBRT by several questionnaires at different times including the following: Edmonton Symptom Assessment System (ESAS), Brain Symptom and Impact Questionnaire (BASIQ), Spitzer Questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), EORTC brain module (EORTC QLQ-BN20+2), EORTC QLQ-C15-PAL, and Functional Assessment of Cancer Therapy-General (FACT-G). Questionnaires were grouped for analysis by Wilcoxon Signed Rank test according to the scale of ranking into 0-10, 1-4, and 0-4. RESULTS: Thirty-six patients were interviewed with the ESAS or BASIQ. The median age was 65 years old, and median Karnofsky Performance Status (KPS) was 70. There was a significant increase in fatigue score from baseline to month 1 (p=0.02), and months 2 and 3 had no significant change. There was a significant correlation between fatigue and overall QOL score at baseline and month 1 (p=0.01, p<0.0001), respectively. Two hundred and twenty-eight patients were surveyed with Spitzer, C15-PAL, BN20+2, QLQ-C30, or FACT-G. Median age was 64 years old and median KPS was 80. Compared to baseline, fatigue score was significantly higher at month 1 (p<0.0001) and month 2 (p=0.001), with no significant change at month 3. Significant correlation was found between fatigue and overall QOL at baseline, months 1, 2 (p<0.0001), and 3 (p=0.0009). For all groups, there was no significant change in fatigue score between patients with or without dexamethasone (Dx), except for the fatigue changed score of the group with scale 0-4. CONCLUSIONS: Fatigue was significantly increased from baseline to month 1 in all patients, and most patients experienced no difference in fatigue if they were receiving Dx. Increased fatigue was significantly related with decreased overall QOL.

Validation of the Polish version of the EORTC QLQ-BM22 module for the assessment of health-related quality of life in patients with bone metastases.

PURPOSE: The aim of our study was to undertake a prospective validation study of the Polish version of the European Organization for Research and Treatment of Cancer (EORTC) bone metastases (QLQ-BM22) module used alongside the EORTC core measure. METHODS: The translated module was pilot-tested according to the established EORTC guidelines. Patients with histological confirmation of malignancy and bone metastases, diagnosed by imaging studies, were eligible for the study. All patients filled out the Polish version of the QLQ-BM22 module in addition to QLQ-C30 and a demographic questionnaire. Standard validity and reliability analyses were performed. RESULTS: One hundred and fifty-five patients were enrolled into the study, including 94 women (60.7 %) and 61 men (mean age ± SD; 59.1 ± 12.1). Cronbach's alpha coefficients, range 0.68-0.93, showed positive internal consistency. Re-test was undertaken with fifty patients (32.3 %). Interclass correlations for the EORTC QLQ-BM22 ranged from 0.91 to 0.93 and proved sufficient test-retest reliability. Satisfactory convergent and discriminant validity in multi-trait scaling analyses was seen. CONCLUSIONS: Our study provides new and robust evidence which shows that the Polish version of the QLQ-BM22 module is a valid and reliable instrument for measuring health-related quality of life in patients with bone metastases. It is suitable for use in clinical trials and in research.

Minimal clinically important differences in the brief pain inventory in patients with bone metastases.

PURPOSE: The brief pain inventory (BPI) is often used to assess pain and functional interference as a result of pain in cancer patients. Minor improvements or deteriorations in BPI may be statistically significant due to large sample sizes but may not necessarily be clinically relevant. The purpose of this study was to determine the minimal clinically important differences (MCID) in the functional BPI in patients with pain due to bone metastases. METHODS: BPI scores were collected from patients with painful bone metastases who visited the Rapid Response Radiotherapy Program for palliative radiotherapy. Pain and functional interferences scores were also collected monthly for three months. Patients were categorized into "complete or partial response," "pain progression," and "indeterminate response" based on their pain scores as recommended by the latest consensus definitions. Anchor-based determination of MCIDs of functional interference scores was calculated by determining the difference between the mean follow-up scores and the mean baseline scores for patients from each of the three response groups. Distribution-based estimates were obtained utilizing 0.2, 0.3, and 0.5 standard deviation (SD) effect sizes and the standard error of measurement. The anchor-based method results were compared with the distribution-based method results. RESULTS: Statistically significant MCIDs were determined for all of the functional interference items of BPI for patients with "complete or partial response"; whereas, no statistically significant MCIDs in BPI scores could be determined for patients with "pain progression." Some of the functional interference items of BPI had statistically significant MCIDs for patients with "indeterminate response," although these were generally smaller than patients with complete or partial response. Using the distribution-based approach, an effect size of 0.5 SD was the closest estimate for determining the MCID for both patients with complete or partial response and those with indeterminate response. CONCLUSIONS: The MCIDs determined for pain improvement were rather large, where as statistically significant MCIDs could not be detected for pain deterioration. Knowledge of MCIDs utilizing the BPI will allow physicians to evaluate the impact of treatment (or no treatment) on a patient's functional abilities. Knowledge of MCIDs may allow for sample size determination in future clinical trials.

International radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting.

PURPOSE: This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). METHODS: Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. RESULTS: One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. CONCLUSIONS: Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.

Conventionally fully fractionated Gamma Knife Icon re-irradiation of primary recurrent intracranial tumors: the first report indicating feasibility and safety.

OBJECTIVE: With the incorporation of real-time image guidance on the Gamma Knife system allowing for mask-based immobilization (Gamma Knife Icon [GKI]), conventionally fully fractionated (1.8-3.0 Gy/day) GKI radiation can now be delivered to take advantage of an inherently minimal margin for delivery uncertainty, sharp dose falloff, and inhomogeneous dose distribution. This case series details the authors' preliminary experience in re-irradiating 7 complex primary intracranial tumors, which were considered to have been previously maximally radiated and situated adjacent to critical organs at risk. METHODS: The authors retrospectively reviewed all patients who received fractionated re-irradiation using GKI at the Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada, between 2016 and 2021. Patients with brain metastases, and those who received radiotherapy courses in 5 or fewer fractions, were excluded. All radiotherapy doses were converted to the equivalent total dose in 2-Gy fractions (EQD2), with the assumption of an α/ß ratio of 2 for late normal tissue toxicity and 10 for the tumor. RESULTS: A total of 7 patients were included in this case series. Three patients had recurrent meningiomas, as well as 1 patient each with ependymoma, intracranial sarcoma, pituitary macroadenoma, and papillary pineal tumor. Six patients had undergone prior linear accelerator-based conventional fractionated radiotherapy and 1 patient had undergone prior proton therapy. Patients were re-irradiated with a median (range) total dose of 50.4 (30-63.4) Gy delivered in a median (range) of 28 (10-38) fractions with GKI. The median (range) target volume was 6.58 (0.2-46.3) cm3. The median (range) cumulative mean EQD2 administered to the tumor was 121.1 (107.9-181.3) Gy, and the median (range) maximum point EQD2 administered to the brainstem, optic nerves, and optic chiasm were 91.6 (74.0-111.5) Gy, 58.9 (6.3-102.9) Gy, and 59.9 (36.7-127.3) Gy, respectively. At a median (range) follow-up of 15 (6-42) months, 6 of 7 patients were alive with 4 having locally controlled disease. Only 3 patients experienced treatment-related toxicities, which were self-limited. CONCLUSIONS: Fractionated radiotherapy using GKI may be a safe and effective method for the re-irradiation of complex progressive primary intracranial tumors, where the aim is to minimize the potential for serious late effects.

Comparison of pain response and functional interference outcomes between spinal and non-spinal bone metastases treated with palliative radiotherapy.

PURPOSE: The purpose of this study was to compare functional interference and pain response outcomes using the Brief Pain Inventory (BPI) for patients treated with palliative radiotherapy to spine versus non-spine bones and determine if dose fractionation was associated with each group's respective response. MATERIALS AND METHODS: Patients treated for painful bone metastases with palliative radiotherapy during May 2003 to June 2007 were analyzed. The BPI was utilized at baseline and monthly for 6 months post-radiation. Pain response was determined using International Bone Metastases Consensus response definitions. Wilcoxon rank-sum test (for continuous variable), Fisher exact test (for categorical value), and two-way analysis of variance were used for comparisons, and a p value of ≤ 0.05 was considered statistically significant. RESULTS: Three hundred eighty-six patients were analyzed, 62% were treated with a single fraction, 38% with multiple fractions. Pain and functional interference scores significantly improved over time in both spine and non-spine sites. At 3 months, 42% of all patients had a partial response, and 25% had a complete response. Location of bone metastases and radiotherapy dose were not predictive factors for pain response nor functional interference following radiation treatment. CONCLUSION: Spine and non-spine bone metastases exhibited similar pain and functional interference improvements over a period of 6 months post-radiotherapy. There were, however, high attrition rates as expected with palliative studies, with approximately half the patients remaining in this study by 3 months and a fifth by 6 months. A single 8 Gy resulted in equal benefits in terms of both pain response and improvement in function.

Symptom clusters in patients with bone metastases--a reanalysis comparing different statistical methods.

PURPOSE: The aims of this study were to determine whether symptom clusters in patients with bone metastases varied when derived using three different statistical methods and to compare the presentation of symptom clusters over time in responders and nonresponders to palliative radiation treatment (RT). METHODS: Secondary analysis of a previously reported data set compiled using the brief pain inventory from 348 patients with bone metastases. Hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA) were performed to identify symptom clusters at baseline, 1, 2, and 3 months following radiation treatment. Clusters derived were compared with the findings obtained using principal component analysis (PCA) in our previous study. The total patient sample was further separated into two subgroups: responders and nonresponders to RT. PCA, HCA, and EFA identified symptom clusters experienced by each subgroup at the same time points as before. RESULTS: Little correlation was observed in the symptom cluster findings of PCA, EFA, and HCA in the total patient sample. Absolute consensus among all three statistical methods was never reached at any assessment time point in the present study. Varying patterns of symptom cluster presentation over time were observed in the responders versus nonresponders subgroups regardless of the analytical method employed. A core cluster of symptoms composed of worst pain, general activity, walking ability, normal work, and enjoyment of life frequently presented in the same cluster. CONCLUSION: The presence and composition of symptom clusters derived varied depending on which statistical analysis method was employed. A key step in attaining consistency in symptom cluster research necessitates the utilization of a common method.

Comparing baseline symptom severity and demographics over two time periods in an outpatient palliative radiotherapy clinic.

PURPOSE: The primary objective of this study was to compare the symptom severity in two different patient populations assessed in an outpatient palliative radiotherapy clinic over two time periods spanning 10 years. The secondary objective was to assess any changes in the baseline demographics of these patients. METHODS: Data were collected from 1999 to 2009. Upon initial presentation to the clinic, the Edmonton Symptom Assessment Scale (ESAS) was administered to patients to capture symptom severity. This validated assessment tool asks patients to score their level of pain, tiredness, nausea, depression, anxiety, drowsiness, loss of appetite, well-being, and dyspnea on an 11-point Likert scale. Differences between the two patient groups were assessed using chi-squared analysis and Wilcoxon rank-sum tests. A p value of <0.05 was considered significant. RESULTS: A total of 1,439 patients completed the ESAS from 1999 to 2009. Patients were divided into two time periods 1999-2002 (n = 689) and 2006-2009 (n = 750). Pain, depression, nausea, fatigue, anxiety, drowsiness, and dyspnea were significantly better in 2006-2009 (p < 0.0001). Loss of appetite was not statistically different between the two time periods (p = 0.236). Significantly more patients with genitourinary cancers (p = 0.03) or a referral for a mass (p < 0.0001) were seen in 2006-2009. More patients with breast cancer (p = 0.04) and bone pain (p = 0.0002) were seen in 1999-2002. The median age was significantly higher (70 years vs. 68 years, p = 0.03) for patients seen in 2006-2009. No significant differences were seen in performance status or gender between the two groups. CONCLUSION: There have been statistically significant lower scores in the severity of the majority of symptoms as scored by the latter patient cohort; however, whether this difference in magnitude is clinically significant is debatable. The reason for referral and demographics in patients sent for palliative radiotherapy has changed over a 10-year period. This may be a reflection of the changes in systemic therapies and improvements in supportive care for patients with advanced cancer.

Fatigue in advanced cancer patients attending an outpatient palliative radiotherapy clinic as screened by the Edmonton Symptom Assessment System.

INTRODUCTION: Advanced cancer patients present with a variety of physical and psychological symptoms. Fatigue is one such symptom which reduces overall quality of life and is difficult to manage. The purpose of this study was to report the presence, severity, and correlating factors of fatigue in advanced cancer patients attending an outpatient palliative radiotherapy clinic. MATERIALS/METHODS: Patients referred to the Rapid Response Radiotherapy Program between January 1999 and October 2009 completed the Edmonton Symptom Assessment System (ESAS) prior to consultation. Demographic information including age, Karnofsky Performance Status (KPS), gender, and primary cancer sites were collected. Ordinal logistic regression analysis was conducted to determine relationships between demographic information, other ESAS items, and levels of fatigue. Multivariate ordinal logistic regression analysis was used to determine the most significant predictors of fatigue. A p value of <0.05 was considered statistically significant. RESULTS: A total of 1,397 patients completed the ESAS prior to consultation. Median age was 68 years (range, 21-95), median KPS was 60 (range, 10-100), and slightly more males completed the ESAS (53.0%). Common primary cancers were of the lung (35.8%), breast (20.7%), and prostate (17.7%). Only 179 (12.8%) patients reported no fatigue; the majority of patients reported moderate (31.8%) or severe (34.4%) fatigue. A low KPS (p < 0.0001), being female (p = 0.0056), or being referred for bone metastases (p = 0.0185) significantly correlated with higher levels of fatigue. Patients with a genitourinary primary cancer (p = 0.0078) and/or referred for malignant spinal cord compression (p = 0.0004) reported less fatigue. All other ESAS items were significantly related to fatigue. The most significant predictors of fatigue were pain (p < 0.0001, odds ratio (OR) = 1.07), nausea (p = 0.0010, OR = 1.10), depression (p < 0.0001, OR = 1.10), drowsiness (p < 0.0001, OR = 1.33), dyspnea (p = 0.0003, OR = 1.08), and overall well-being (p < 0.0001, OR = 1.19). CONCLUSION: Moderate fatigue was reported in over 66% of our advanced cancer patients prior to radiotherapy. Since radiotherapy inherently causes fatigue, proactive and multidisciplinary management is required for these patients. Similar rates of fatigue severity, in lengthier, fatigue-specific tools, suggest that the ESAS may be a good tool for screening the advanced cancer population.

EORTC QLQ-C15-PAL quality of life scores in patients with advanced cancer referred for palliative radiotherapy.

PURPOSE: Symptom control and improved quality of life (QOL) are primary goals of treatment in palliative oncology. The present study assessed and compared patient demographics, baseline Karnofsky Performance Status (KPS) and QOL using the QLQ-C15-PAL questionnaire prior to palliative radiotherapy (RT) for bone, brain, or lung disease. Few studies have used this questionnaire, an abbreviated version that was developed by the European Organization for Research and Treatment of Cancer specifically for patients with advanced cancer to decrease the burden of completing the longer, more time-consuming QLQ-C30. METHODS: Patients referred to an outpatient palliative RT clinic completed QLQ-C15-PAL questionnaires prior to palliative RT for bone, brain, or lung cancer sites. The associations between baseline QLQ-C15-PAL functional/symptom scales, patient demographics, and clinical variables including KPS were explored. RESULTS: When data from all 369 patients were analyzed, higher KPS scores correlated significantly with better overall QOL and higher physical and emotional functioning. The QLQ-C15-PAL provided more detailed information regarding how symptom burden varied depending on disease site. Patients with bone metastases had worse QLQ-C15-PAL scores for pain, while those with brain and lung disease had worse scores for fatigue. Other health-related QOL scores measured by the QLQ-C15-PAL varied as a function of age and gender. CONCLUSION: As the QLQ-C15-PAL provides detailed and often critical information regarding symptom burden, it may eventually be recognized as a universal core questionnaire to assess QOL in this patient population with advanced cancer while relieving the survey burden.

Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative treatment of bone metastases.

PURPOSE: To document the incidence and timing of radiotherapy-induced nausea and vomiting (RINV) in the treatment of bone metastases among patients receiving prophylaxis with a 5-HT(3) receptor antagonist. METHODS: Patients receiving single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron. The frequency and duration of prophylaxis and the use of rescue antiemetics were left to the discretion of the treating physicians. Patients documented episodes of nausea (N) and vomiting (V) in daily diaries before and during RT, and until 10 days following RT completion. Rates of complete prophylaxis (CP) for N&V, respectively (CP = no event and no rescue medication), were calculated for the acute phase (the period from the start of RT to the first day following RT completion inclusive) and the delayed phase (the second to tenth days following RT completion inclusive). RESULTS: Fifty-nine patients were enrolled, and 32 were evaluable. CP rates were as follows: moderate-risk SF group (n = 16), acute phase (CP for N = 56%, CP for V = 69%) and delayed phase (CP for N = 31%, CP for V = 44%); moderate-risk MF group (n = 7), acute phase (CP for N = 71%, CP for V = 57%) and delayed phase (CP for N = 43%, CP for V = 57%); low-risk SF group (n = 8), acute phase (CP for N = 50%, CP for V = 100%) and delayed phase (CP for N = 43%, CP for V = 57%); and low-risk MF group (n = 1), acute phase (CP for N = 100%, CP for V = 100%) and delayed phase (CP for N = 100%, CP for V = 100%). CONCLUSIONS: Despite prophylaxis, RINV was common among patients receiving palliative radiotherapy for bone metastases, especially during the delayed phase.

Do elderly patients with metastatic cancer have worse quality of life scores?

PURPOSE: The purpose of this study is to compare self-reported quality of life (QOL) scores in old and young patients with metastatic cancer using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL questionnaire. MATERIALS AND METHODS: Patients receiving palliative radiotherapy (RT) for bone metastases and brain metastases completed the QLQ-C15-PAL questionnaire prior to treatment. Using multiple linear regression analysis, a parametric test, the QLQ-C15-PAL scores were compared using 65 and 70 years as cutoff ages. RESULTS: A total of 340 patients were referred for palliative RT for bone metastases (n = 190) or brain metastases (n = 150). Physical functioning and appetite were worse in the older group using either 65 or 70 years as the cutoff age. Age-related differences in the QLQ-C15-PAL scores varied as a function of age cutoff used and location of metastatic site irradiated. CONCLUSION: Based on the (EORTC) QLQ-C15-PAL, elderly advanced cancer patients have a different QOL profile. Similar observations have been reported with the (EORTC) QLQ-C30 questionnaire.

Symptom clusters in patients with advanced cancer: sub-analysis of patients reporting exclusively non-zero ESAS scores.

BACKGROUND: Advanced cancer patients often experience multiple concurrent symptoms, which can have prognostic effects on patients' quality of life. Including patients who did not experience all of the symptoms measured by an assessment tool may interfere with accurate symptom cluster identification. Varying statistical methods may also contribute to inconsistencies of cluster results. AIMS: To compare symptom clusters in a subgroup of patients reporting exclusively non-zero ESAS scores with those in the total patient sample. To examine whether using different statistical methods results in varied symptom clusters. DESIGN: Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA) and Exploratory Factor Analysis (EFA) were performed on the 'non-zero' subgroup and the total patient sample to identify symptom clusters at baseline and weeks 1, 2, 4, 8 and 12 following palliative radiotherapy. SETTING/PARTICIPANTS: A previous single-centre study used Principal Component Analysis to explore symptom clusters in 1296 advanced cancer patients. The present study analyzed this previously reported data set. RESULTS: Notably different symptom clusters were extracted between the two patient groups regardless of the statistical method at baseline, with the exception of a cluster composed of drowsiness, fatigue and dyspnea using Principal Component Analysis and Hierarchical Cluster Analysis. At follow-ups, different statistical methods yielded significantly varied symptom clusters. Only anxiety, depression and well-being consistently occurred in the same cluster across methods and over time. CONCLUSIONS: The composition of symptom clusters varied depending on if patients with non-zero scores were excluded at baseline and on the statistical method employed. Identifying valid clusters may prove useful for bettering symptom diagnosis and management for cancer patients.

Prostate cancer pathology audits: is central pathology review still warranted?

INTRODUCTION: Estimating the risk of extraprostatic extension and the probability of recurrence with different treatment modalities is common practice in cancer management. A strong predictor of recurrence and organ-confined disease is tumor grade. However, differences exist between genitourinary and non-specialist pathologists in grading prostate cancer. As such, the primary objective of this study was to assess the accuracy of non-specialist prostate cancer biopsies at our institution by analyzing the proportion of cases changing pathologic risk category upon expert review. MATERIALS AND METHODS: Log books from 2003 where our genitourinary pathologists reviewed prostate needle-core biopsies were used to identify cases. A retrospective chart review was completed and descriptive statistics were used to summarize the results for the following synoptic variables: 10 and 20 Gleason Score, number of biopsy sites, overall % involvement, perineural invasion--PNI (present/absent), extracapsular extension--ECE (present/absent). RESULTS: A total of 151 patients were reviewed. Twenty eight percent of cases (42/151) had a change in risk category after expert review. Of the 98 low risk cases, 33% were upgraded in risk category. Of the 24 intermediate risk cases, 12% were upgraded to high risk and none were downgraded. Of the 29 high risk cases, 24% were downgraded in risk category. CONCLUSION: All referred patients should continue to have their pathology centrally reviewed. This practice will help facilitate optimal prostate cancer management and improve quality of care. While these findings are dated given pathologic practice change, such changes do not necessarily equate with disparity elimination or reduction; conclusions can only be drawn with a more recent audit to see if such disparities still exist.

Skull phantom-based methodology to validate MRI co-registration accuracy for Gamma Knife radiosurgery.

PURPOSE: Target localization, for stereotactic radiosurgery (SRS) treatment with Gamma Knife, has become increasingly reliant on the co-registration between the planning MRI and the stereotactic cone-beam computed tomography (CBCT). Validating image registration between modalities would be particularly beneficial when considering the emergence of novel functional and metabolic MRI pulse sequences for target delineation. This study aimed to develop a phantom-based methodology to quantitatively compare the co-registration accuracy of the standard clinical imaging protocol to a representative MRI sequence that was likely to fail co-registration. The comparative methodology presented in this study may serve as a useful tool to evaluate the clinical translatability of novel MRI sequences. METHODS: A realistic human skull phantom with fiducial marker columns was designed and manufactured to fit into a typical MRI head coil and the Gamma Knife patient positioning system. A series of "optimized" 3D MRI sequences-T1 -weighted Dixon, T1 -weighted fast field echo (FFE), and T2 -weighted fluid-attenuated inversion recovery (FLAIR)-were acquired and co-registered to the CBCT. The same sequences were "compromised" by reconstructing without geometric distortion correction and re-collecting with lower signal-to-noise-ratio (SNR) to simulate a novel MRI sequence with poor co-registration accuracy. Image similarity metrics-structural similarity (SSIM) index, mean squared error (MSE), and peak SNR (PSNR)-were used to quantitatively compare the co-registration of the optimized and compromised MR images. RESULTS: The ground truth fiducial positions were compared to positions measured from each optimized image volume revealing a maximum median geometric uncertainty of 0.39 mm (LR), 0.92 mm (AP), and 0.13 mm (SI) between the CT and CBCT, 0.60 mm (LR), 0.36 mm (AP), and 0.07 mm (SI) between the CT and T1 -weighted Dixon, 0.42 mm (LR), 0.23 mm (AP), and 0.08 mm (SI) between the CT and T1 -weighted FFE, and 0.45 mm (LR), 0.19 mm (AP), and 1.04 mm (SI) between the CT and T2 -weighted FLAIR. Qualitatively, pairs of optimized and compromised image slices were compared using a fusion image where separable colors were used to differentiate between images. Quantitatively, MSE was the most predictive and SSIM the second most predictive metric for evaluating co-registration similarity. A clinically relevant threshold of MSE, SSIM, and/or PSNR may be defined beyond which point an MRI sequence should be rejected for target delineation based on its dissimilarity to an optimized sequence co-registration. All dissimilarity thresholds calculated using correlation coefficients with in-plane geometric uncertainty would need to be defined on a sequence-by-sequence basis and validated with patient data. CONCLUSION: This study utilized a realistic skull phantom and image similarity metrics to develop a methodology capable of quantitatively assessing whether a modern research-based MRI sequence can be co-registered to the Gamma Knife CBCT with equal or less than equal accuracy when compared to a clinically accepted protocol.