Charles Catton

Cancer-related fatigue and associated disability in post-treatment cancer survivors.

PurposeCancer-related fatigue (CRF) is the most prevalent and distressing symptom among cancer patients and survivors. However, research on its prevalence and related disability in the post-treatment survivorship period remains limited. We sought to describe the occurrence of CRF within three time points in the post-treatment survivorship trajectory.MethodsA self-administered mail-based questionnaire which included the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and the World Health Organisation Disability Assessment Schedule 2.0 was sent to three cohorts of disease-free breast, prostate or colorectal cancer survivors (6–18 months; 2–3 years; and 5–6 years post-treatment). Clinical information was extracted from chart review. Frequencies of significant fatigue by diagnostic group and time cohorts were studied and compared. Multivariate logistic regressions were conducted to examine the associations between CRF and demographic, clinical, and psychosocial variables.ResultsOne thousand two hundred ninety-four questionnaire packages were returned (63xa0% response rate). A total of 29xa0% (95xa0% CI [27xa0% to 32xa0%]) of the sample reported significant fatigue (FACT-F ≤34), and this was associated with much higher levels of disability (pu2009<u20090.0001). Breast (40xa0% [35xa0% to 44xa0%]) and colorectal (33xa0% [27xa0% to 38xa0%]) cancer survivors had significantly higher rates of fatigue compared with the prostate group (17xa0% [14xa0% to 21xa0%]) (pu2009<u20090.0001). Fatigue levels did not differ between the three time cohorts. The main factors associated with CRF included physical symptom burden, depression, and co-morbidity (AUC, 0.919 [0.903 to 0.936]).ConclusionsClinically relevant levels of CRF are present in approximately 1/3 of cancer survivors up to 6xa0years post-treatment, and this is associated with high levels of disability.Implications for Cancer SurvivorsClinicians need to be aware of the chronicity of CRF and assess for it routinely in medical practice. While there is no gold standard treatment, non-pharmacological interventions with established efficacy can reduce its severity and possibly minimize its disabling impact on patient functioning. Attention must be paid to the co-occurrence and need for possible treatment of depression and other co-occurring physical symptoms as contributing factors.

Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.

PURPOSEnTo compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone.nnnMETHODS AND MATERIALSnPatient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT. Kaplan-Meier survival analysis was performed to compare differences in bFFS (primary endpoint) and OS in the 3 matched groups.nnnRESULTSnPropensity score matching created acceptable balance in the baseline prognostic factors in all matches. Final matches included 2 1:1 matches in the intermediate-risk cohorts, LDR-BT versus EBRT (total n=254) and HDR-BT+EBRT versus EBRT (total n=388), and one 4:1 match in the low-risk cohort (LDR-BT:EBRT, total n=400). Median follow-up ranged from 2.7 to 7.3 years for the 3 matched cohorts. Kaplan-Meier survival analysis showed that all BT treatment options were associated with statistically significant improvements in bFFS when compared with EBRT in all cohorts (intermediate-risk EBRT vs LDR-BT hazard ratio [HR] 4.58, P=.001; intermediate-risk EBRT vs HDR-BT+EBRT HR 2.08, P=.007; low-risk EBRT vs LDR-BT HR 2.90, P=.004). No significant difference in OS was found in all comparisons (intermediate-risk EBRT vs LDR-BT HR 1.27, P=.687; intermediate-risk EBRT vs HDR-BT+EBRT HR 1.55, P=.470; low-risk LDR-BT vs EBRT HR 1.41, P=.500).nnnCONCLUSIONSnPropensity score matched analysis showed that BT options led to statistically significant improvements in bFFS in low- and intermediate-risk prostate cancer patient populations.

The prostate cancer risk stratification (ProCaRS) project: recursive partitioning risk stratification analysis.

BACKGROUNDnThe Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema.nnnMETHODSnThe RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively.nnnRESULTSnThe recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30).nnnCONCLUSIONSnProposed RS subcategories have been identified by a RPA of the ProCaRS database.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists.

PURPOSEnThe purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists.nnnMETHODS AND MATERIALSnRadiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics.nnnRESULTSnTen radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate.nnnCONCLUSIONSnFor preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

Results of Resection for Recurrent or Residual Retroperitoneal Sarcoma After Failed Primary Treatment

BackgroundLocal recurrence after resection of retroperitoneal sarcoma (RPS) is a common and difficult problem. Gross residual disease after incomplete resection is a particular challenge. The authors reviewed their experience with patients referred for management of recurrent or residual RPS.MethodsPatients seen at the authors’ center from 1996 to 2013 who had undergone resection at an outside institution were identified from a prospective database. Kaplan–Meier survival curves were generated and compared by log-rank analysis.ResultsA total of 45 patients were referred with recurrent (nxa0=xa033) or residual (nxa0=xa012) disease. Before initial surgery elsewhere, cross-sectional imaging (computed tomograpy/magnetic resonance imaging) had been obtained for 30 patients (67xa0%) and percutaneous biopsy for 8 patients (18xa0%). At referral to the authors’ center, 15 patients were deemed inappropriate for resection, with a subsequent median overall survival (OS) period of 15xa0months. At the authors’ center, 30 patients (22 with recurrent and 8 with residual disease) were resected. The majority received preoperative radiation (77xa0%). The postoperative mortality rate was 0xa0% in the recurrent group and 25xa0% (2/8) in the residual group (pxa0=xa00.015). Among the 30 resected patients, the median and 5-year OS was 53 months (50xa0%), and the OS was better in the recurrent group (median, 77 months) than in the residual group (median, 41xa0months (pxa0=xa00.027). The median time to local re-recurrence was 49xa0months in the recurrent group and 35xa0months in the residual group (pxa0=xa00.730).ConclusionsDurable disease control and prolonged survival may be achieved for selected patients with recurrent RPS. In this study, resection after previous grossly incomplete resection was associated with high postoperative mortality and inferior OS. The benefit of extensive surgery for these patients may be limited.

Locally Advanced Prostate Cancer: Current Controversies and Optimisation Opportunities.

Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

Survival outcomes for cutaneous angiosarcoma of the scalp versus face: Angiosarcoma of scalp and face

The primary purpose of this study was to examine whether angiosarcoma outcomes differ for the scalp and face.

Stereotactic Ablative Radiotherapy Versus Low Dose Rate Brachytherapy or External Beam Radiotherapy: Propensity Score Matched Analyses of Canadian Data

AIMSnTo compare biochemical failure-free survival (BFFS) and overall survival for prostate cancer treated with stereotactic ablative radiotherapy (SABR), low dose rate (LDR) brachytherapy or external beam radiotherapy (EBRT) using a large Canadian multi-institutional database.nnnMATERIALS AND METHODSnPatients with low risk localised prostate cancer treated with SABR, LDR or EBRT and no androgen deprivation therapy were selected. Propensity score matching was used to create two sets of matched cohorts with LDR and EBRT serving as control groups. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare differences in BFFS and overall survival between treatment groups.nnnRESULTSnThe pre-matched cohort contained 602 patients; the median follow-up was >5.0 years. There were no significant differences in BFFS before or after matching for SABR versus LDR but the prostate-specific antigen (PSA) nadir was lower after LDR. For the SABR versus EBRT, SABR had a BFFS trend before matching (Pxa0=xa00.08), which became significant after matching (Pxa0<xa00.001).nnnCONCLUSIONSnUsing the Genitourinary Radiation Oncologists of Canada Prostate Cancer Risk Stratification database, low risk prostate cancer patients receiving SABR had similar BFFS compared with patients receiving LDR but better BFFS than EBRT patients. Further comparative studies of efficacy, quality of life and economic outcomes using a broader risk of patients are warranted.

Evaluation of high dose volumetric CT to reduce inter-observer delineation variability and PTV margins for prostate cancer radiotherapy

PURPOSEnThe aim was to determine whether the enhanced soft tissue contrast provided by high-dose volumetric CT (HDVCT) can reduce inter-observer variability in delineating prostate compared to helical conventional CT (CCT) scans and 3T MRI scans for patients undergoing radical prostate cancer radiotherapy. Secondly, to quantify the potential PTV reduction with decreased inter-observer variability.nnnMATERIALS AND METHODSnA 320 slice volumetric CT scanner was used. The wide-detector coverage of 16cm enabled volumetric image acquisition of prostate gland in one rotation. Three imaging studies were performed on ten patients. CCT and HDVCT were performed consecutively at the same coordinate system followed by MRI. Five radiation oncologists delineated the prostate.nnnRESULTSnThe inter-observer variability is 2.0±0.6, 1.9±0.4 and 1.8±0.4mm for CCT, HDVCT and MR respectively with the maximum at the apex region. Comparing inter-observer difference variability between CCT and HDVCT with MR indicates that observers have larger variations in contouring using CCT than HDVCT especially at apex. Jaccard index of HDVCT is significantly higher than CCT with a mean difference of 0.03 (p=0.011). Both MRI and HDVCT provide the opportunity for a 2mm PTV margin reduction at the apex compared to CCT.nnnCONCLUSIONnInter-observer variability in delineation remains an important source of systematic error. HDCTV for treatment planning reduces this error without recourse to MRI and permits a PTV reduction of 2mm at the apex. The margins required to account for residual error with any imaging modality are still greater than are used in typical current practice.

Improved outcomes with dose escalation in localized prostate cancer treated with precision image-guided radiotherapy

BACKGROUND AND PURPOSEnDose-escalated radiotherapy (DE) improves outcomes in localized prostate cancer (PCa). The impact of DE in the context of image-guided radiotherapy (IGRT) remains unknown. Herein, we determined outcomes of three sequential cohorts treated with progressive DE-IGRT.nnnMATERIALS AND METHODSnWe analyzed data from 1998 to 2012. Patients treated with radical radiotherapy were included, with three sequential institutional schedules: (A) 75.6Gy, (B) 79.8Gy, (C) 78Gy, with 1.8, 1.9 and 2Gy/fraction, respectively. IGRT consisted of fiducial markers and daily EPID (A, B) or CBCT (C).nnnRESULTSn961 patients were included, with median follow-up of 6.1y. 30.5%, 32.6% and 36.9% were treated in A, B and C, respectively. Risk category distribution was 179 (18.6%) low-, 653 (67.9%) intermediate- and 129 (13.5%) high-risk. PSA, T-category, androgen deprivation use and risk distribution were similar among groups. BCR (biochemical recurrence) was different (p<0.001) between A, B and C with 5-year rates of 23%, 17% and 9%, respectively (HR 2.68 [95% CI 1.87-3.85] and 1.92 [95% CI 1.33-2.78] for A and B compared to C, respectively). Findings were most significant in the intermediate-risk category. Metastasis, cause-specific-death and toxicities were not different between cohorts.nnnCONCLUSIONnOur findings suggest continuous BCR improvement with progressive DE-IGRT. Prospective validation considering further DE with IGRT seems warranted.