Milica Milakovic

Radiotherapy for the prophylaxis of heterotopic ossification: a systematic review and meta-analysis of published data.

INTRODUCTION Following surgery, the formation of heterotopic ossification (HTO) can limit mobility and impair quality of life. Radiotherapy has been proven to provide efficacious prophylaxis against HTO, especially in high-risk settings. PURPOSE The current review aims to determine the factors influencing HTO formation in patients receiving prophylactic radiotherapy. METHODS A systematic search of the literature was conducted on Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Studies were included if they reported the percentage of sites developing heterotopic ossification after receiving a specified dose of prophylactic radiotherapy. Weighted linear regression analysis was conducted for continuous or categorical predictors. RESULTS Extracted from 61 articles, a total of 5464 treatment sites were included, spanning 85 separate study arms. Most sites were from the hip (97.7%), from United States patients (55.2%), and had radiation prescribed postoperatively (61.6%) at a dose of 700cGy (61.0%). After adjusting for radiation site, there was no statistically significant relationship between the percentage of sites developing HTO and radiation dose (p=0.1) or whether radiation was administered preoperatively or postoperatively (p=0.1). Sites with previous HTO formation were more likely to develop recurrent HTO than those without previous HTO formation (p=0.04). There was a statistically significant negative relationship between the HTO development and the cohort mean year of treatment (p=0.007). CONCLUSION Decreases in rates of HTO over time in this patient population may be a function of more efficacious surgical regimens and prophylactic radiotherapy.

Radiotherapy for the prophylaxis of heterotopic ossification: A systematic review and meta-analysis of randomized controlled trials

INTRODUCTION Heterotopic ossification (HO) involves the formation of lamellar bone in nonosseous tissue. For HO, radiotherapy has been shown to be an effective prophylactic modality. OBJECTIVE To compare HO outcomes following radiotherapy and to investigate the comparative efficacy of preoperative versus postoperative radiotherapy. METHODS A systematic search was conducted on Ovid MEDLINE, EMBASE and Cochrane CENTRAL. Studies were included if they were randomized controlled trials (RCTs) that included patients who were prescribed prophylactic radiation for whom relevant HO progression outcomes were reported. RESULTS From a literature search of 528 articles, 12 RCTs were included. There was a statistically significant reduction in HO prevalence with multiple as opposed to single fraction radiotherapy (p=0.04), however there was no statistically significant difference when examining HO progression (p=0.34). There was no statistically significant difference in HO progression when comparing a biologically effective radiation dose (BED) of >2500cGy versus ⩽2500cGy (p=0.28). As well, no statistically significant difference existed in HO progression between postoperative versus preoperative radiation (p=0.43). CONCLUSION There was no difference between postoperative or preoperative radiotherapy in preventing HO progression. There seems to be no relationship between BED greater or less than 2500cGy and the efficacy of HO prophylaxis. Multiple fractions seem to be more effective than single fraction radiotherapy in preventing HO progression.

The impact of psychosocial intervention on survival in cancer: a meta-analysis.

BACKGROUND The impact of psychosocial interventions on survival remains controversial in patients with cancer. A meta-analysis of the recent literature was conducted to evaluate the potential survival benefit associated with psychosocial interventions for cancer patients. METHODS MEDLINE, EMBASE, and Cochrane Central were searched from January 2004 to May 2015 for all randomized controlled trials (RCTs) that compared survival outcomes between cancer patients receiving a psychosocial intervention and those receiving other, or no interventions. Endpoints included one-, two-, and four-year overall survival. Subgroup analyses were performed to compare group-versus individually-delivered interventions, and to assess breast cancer-only trials. RESULTS Of 5,080 identified articles, thirteen trials were included for analysis. There was a significant survival benefit for the intervention group at one year [risk ratio (RR) =0.82; 95% confidence interval (CI), 0.67-1.00; P=0.04] and two years (RR =0.86; 95% CI, 0.78-0.95; P=0.003). However, no significant difference was detected at four years (RR =0.94; 95% CI, 0.85-1.04; P=0.24). Among patients with breast cancer, there was a significant survival benefit of psychosocial interventions at one year (RR =0.59; 95% CI, 0.42-0.82; P=0.002), but no difference at two years (RR =0.82; 95% CI, 0.67-1.02; P=0.07) or four years (RR =0.95; 95% CI, 0.73-1.23; P=0.68). Group-delivered interventions had a significant survival benefit favouring the intervention group at one year (RR =0.57; 95% CI, 0.41-0.79; P=0.0008), but no difference at two years (RR =0.84; 95% CI, 0.68-1.02; P=0.08) or four years (RR =0.94; 95% CI, 0.75-1.20; P=0.64). Individually-delivered interventions had no significant survival benefit at one year (RR =0.92; 95% CI, 0.79-1.08; P=0.32), two years (RR =0.87; 95% CI, 0.75-1.00; P=0.05), or four years (RR =0.93; 95% CI, 0.84-1.04; P=0.21). CONCLUSIONS For the main analysis and group-delivered treatments, psychosocial interventions demonstrated only short-term improvements in survival. Individually-delivered interventions failed to show any survival benefit. Future studies with longer follow-up are warranted to investigate long-term survival outcomes.

Re-irradiation for painful bone metastases: evidence-based approach

The prognosis of patients with bone metastases has improved with the advent of increasingly effective systemic treatment and better supportive care. A growing number of bone metastases patients now outlive the duration of benefits from their initial treatment of radiotherapy (RT) while some patients fail to initially respond to RT. As such, re-irradiation (re-RT) may be required. The current review updates the literature on findings in the area of re-RT. In particular, the recent publication of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Symptom Control (SC20) trial shows that an 8 Gy treatment in a single fraction for re-RT is non-inferior and less toxic than 20 Gy in multiple fractions. Furthermore, patients responding to re-RT have experienced superior quality of life (QoL) and complain of less functional interference from pain; this provides a strong case in support of bone metastases patients being offered re-treatment. However, despite such findings, some specific patients will never respond to initial radiation or re-RT. New evidence suggests significant differences in bone markers between responders and non-responders, thus opening the possibility for further research into the use of such biomarkers for predicting prognosis and for the guidance of consequent treatment decisions.

Latest advances in the management of radiation-induced pain flare, nausea and vomiting

Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation-induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed.

Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis

PurposeChemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs.MethodsA literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints—complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications.ResultsA total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint—emesis in the overall phase—had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold.ConclusionsPalonosetron seems to be more efficacious and safe than other 5-HT3RAs—statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patients quality of life, interfere with a patients compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments. METHODS A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases. RESULTS A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting. CONCLUSIONS The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.

Does gender affect self-perceived pain in cancer patients? A meta-analysis

BACKGROUND Pain is reported in approximately 50-70% of cancer patients. Studies on gender differences in perceived pain generally report lower pain thresholds and increased pain prevalence in women, which may be attributed to gender-specific behaviors, stereotypes, and unknown etiological factors. There are sparse and inconclusive results on gender differences in self-perceived pain in the cancer setting. The aim of this article was to examine the effect of gender on baseline perceived pain intensity in cancer patients through a meta-analysis. METHODS A literature search was conducted using Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials [1947-2016] to identify observational studies and controlled trials that reported on gender-specific pain intensity in cancer patients. Using random-effects modeling, weighted mean differences and 95% confidence intervals (CI) were used to estimate the effect of gender on pain severity in cancer patients. A P value of less than 0.05 was considered statistically significant. RESULTS Of the 1,911 search results reviewed, 13 studies were included. The weighted mean difference (95% CI) in pain intensity was as follows: -0.26 (95% CI: -0.57 to 0.04, P=0.09) for the 0-10 Numerical Rating Scale (NRS) group (n=3,752, 9 studies). When restricted to only patients with advanced cancer, the weighted mean difference was -0.08 (95% CI: -0.36 to 0.20, P=0.58) (n=2,762, 4 studies). The weighted mean difference in the Brief Pain Inventory scores between males and females was 0.03 (95% CI: -1.23 to 1.29, P=0.96) (n=521, 4 studies). CONCLUSIONS Baseline perceived pain intensity in cancer patients did not significantly differ based on gender.