May Tsao

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.

Update on the Systematic Review of Palliative Radiotherapy Trials for Bone Metastases

AIMS To update previous meta-analyses of randomised palliative radiotherapy trials comparing single fractions versus multiple fractions. MATERIALS AND METHODS All published randomised controlled trials comparing single fraction versus multiple fraction schedules for the palliation of uncomplicated bone metastases were included in this analysis. Odds ratios and 95% confidence intervals were calculated for each trial. Forest plots were created using a random effects model and the Mantel-Haenszel statistic. RESULTS In total, 25 randomised controlled trials were identified. For intention-to-treat patients, the overall response rate was similar in patients receiving single fractions (1696 of 2818; 60%) and multiple fractions (1711 of 2799; 61%). Complete response rates were 620 of 2641 (23%) in the single fraction arm and 634 of 2622 (24%) in the multiple fraction arm. No significant difference was seen in overall or complete response rates. Pathological fracture did not favour either arm, but spinal cord compression trended towards favouring multiple fractions; however, neither was statistically significant (P = 0.72 and P = 0.13, respectively). Retreatment rates favoured patients in the multiple fraction arm, where the likelihood of requiring re-irradiation was 2.6-fold greater in the single fraction arm (95% confidence interval: 1.92-3.47; P < 0.00001). Repeated analyses excluding drop-out patients did not alter these findings. In general, no significant differences in acute toxicities were seen. CONCLUSION Overall and complete response rates were similar in both intention-to-treat and assessable patients. Single and multiple fraction regimens provided equal pain relief; however, significantly higher retreatment rates occurred in those receiving single fractions.

A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases

To perform a meta‐analysis on newly diagnosed brain metastases patients treated with whole‐brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

Determining the Incidence of Pain Flare Following Palliative Radiotherapy for Symptomatic Bone Metastases: Results From Three Canadian Cancer Centers

PURPOSE To determine the incidence of pain flare following radiotherapy (RT) for painful bone metastases. MATERIALS AND METHODS Patients with bone metastases treated with RT were eligible. Worst pain scores and analgesic consumption were collected before, daily during, and for 10 days after treatment. Pain flare was defined as a 2-point increase in the worst pain score (0-10) compared to baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. Pain flare was distinguished from progression of pain by requiring the worst pain score and analgesic intake return to baseline levels after the increase/flare (within the 10-day follow-up period). RESULTS A total of 111 patients from three cancer centers were evaluable. There were 50 male and 61 female patients with a median age of 62 years (range, 40-89 years). The primary cancers were mainly breast, lung, and prostate. Most patients received a single 8 Gy (64%) or 20 Gy in five fractions (25%). The overall pain flare incidence was 44/111 (40%) during RT and within 10 days following the completion of RT. Patients treated with a single 8 Gy reported a pain flare incidence of 39% (27/70) and, with multiple fractions, 41% (17/41). CONCLUSION More than one third of the enrolled patients experienced a pain flare. Identifying at-risk individuals and managing potential pain flares is crucial to achieve an optimal level of care.

Dexamethasone for the Prophylaxis of Radiation-induced Pain Flare after Palliative Radiotherapy for Symptomatic Bone Metastases: a Phase II Study

AIMS Pain flare occurs in over one-third of patients receiving palliative radiotherapy for bone metastases. A single dose of dexamethasone can decrease the incidence of pain flare during the first 2 days immediately after radiotherapy. We conducted a phase II prospective study to investigate the prophylactic role of prolonged dexamethasone. MATERIALS AND METHODS Patients with bone metastases treated with a single 8Gy were prescribed 8mg dexamethasone just before palliative radiotherapy and for 3 consecutive days after treatment. Worst pain score and analgesic consumption data were collected at baseline and daily for 10 days after treatment. Analgesic consumption was converted into a total daily oral morphine equivalent dose in the analysis. Pain flare was defined (a priori) as a two-point increase in worst pain on an 11-point numeric rating scale compared with baseline with no decrease in analgesic intake, or a 25% increase in analgesic intake with no decrease in worst pain score. To distinguish pain flare from progressive disease, we required that the worst pain score and analgesic intake returned to baseline levels after the increase/flare. RESULTS Forty-one patients were evaluable (32 men, nine women). Their median age was 67 years. The overall incidence of pain flare was 9/41 (22%) within 10 days after the completion of radiotherapy. Most (55%) of these pain flares occurred on day 5. Absence of pain flare was 34/41(83%) and 39/41 (95%) for days 1-5 and 6-10 after the completion of radiotherapy, respectively. CONCLUSION Dexamethasone is effective in the prophylaxis of radiotherapy-induced pain flare after palliative radiotherapy for bone metastases. Randomised studies are needed to confirm this finding.

Phase II study assessing the effectiveness of Biafine cream as a prophylactic agent for radiation-induced acute skin toxicity to the breast in women undergoing radiotherapy with concomitant CMF chemotherapy

PURPOSE To assess the efficacy of Biafine cream in preventing Grade 2 acute radiation dermatitis, according to the National Cancer Institute of Canada skin radiation toxicity criteria in patients undergoing concomitant adjuvant chemotherapy and radiotherapy to the breast. METHODS AND MATERIALS Sixty patients participated in this study. Patients were treated with a lumpectomy followed by concomitant chemotherapy and radiotherapy to the breast. Biafine cream was applied daily, starting on the first day and ending 2 weeks post-radiotherapy. Patients underwent weekly skin assessments throughout radiotherapy and at 2 and 4 weeks after treatment. Outcome measures were assessed using a Skin Assessment Questionnaire that was scored according to the National Cancer Institute of Canada skin radiation toxicity criteria and a self-administered questionnaire that evaluated skin symptoms. RESULTS The maximum skin toxicity observed during the course of treatment was as follows: less than Grade 2 toxicity, 15% (9 patients); Grade 2, 83% (50 patients); Grade 3, 2% (1 patient); Grade 4, 0% (0 patients). The majority of the radiation dermatitis was observed after 3 weeks of radiotherapy. CONCLUSION The majority of patients who underwent concomitant chemo- and radiotherapy for breast cancer developed Grade 2 radiation dermatitis with the use of Biafine cream. However, no treatment delays or interruptions were observed because of skin toxicity.

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials

PurposePalonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT3RAs in CINV prophylaxis.MethodsA literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT3RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT3RA-related adverse events.ResultsSixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT3RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.ConclusionsPalonosetron is safer and more efficacious than other 5-HT3RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.

Advances in Technology for Intracranial Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) refers to a single radiation treatment delivering a high dose to an intra-cranial target localized in three-dimensions by CT and/or MRI imaging. Traditionally, immobilization of the patients head has been achieved using a rigid stereotactic head frame as the key step in allowing for accurate dose delivery. SRS has been delivered by both Cobalt-60 (Gamma Knife®) and linear accelerator (linac) technologies for many decades. The focus of this review is to highlight recent advances and major innovations in SRS technologies relevant to clinical practice and developments allowing for non-invasive frame SRS.

Fractionated stereotactic radiotherapy for the treatment of vestibular schwannomas: combined experience of the Toronto-Sunnybrook Regional Cancer Centre and the Princess Margaret Hospital

PURPOSE To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for vestibular schwannomas in patients treated at two university-affiliated hospitals. METHODS AND MATERIALS Thirty-nine patients were treated between April 1996 and September 2000. The median age was 56 years (range: 29-80), and median maximal tumor diameter was 20 mm (range: 9-40). A total of 11 patients had fifth and/or seventh cranial nerve dysfunction before irradiation; 2 patients had only facial weakness, 5 patients had only facial numbness, and 4 patients had both facial weakness and numbness. Thirty-three patients were treated with primary FSRT, and 6 patients were treated for recurrent or persistent disease after previous surgery. All patients were treated with 6-MV photons using a stereotactic system with a relocatable frame. The 39 patients received 50 Gy in 25 fractions over 5 weeks. Median follow-up was 21.8 months (range: 4.4-49.6). RESULTS Local control was achieved in 37 patients (95%). Two patients experienced deterioration of their symptoms at 3 and 20 months as a result of clinical progression in one case and tumor progression in the other and underwent surgery post FSRT. A total of 19/28 (67.9%) patients preserved serviceable hearing after FSRT. Deterioration of the facial and trigeminal nerves was observed in only 2 patients who were treated with surgery post FSRT. CONCLUSION FSRT provided excellent tumor control with minimal morbidity and good hearing preservation in this cohort of patients. Longer follow-up is required to confirm long-term control rates.

Re-irradiation for painful bone metastases - a systematic review.

The purpose of this review was to determine the efficacy of re-irradiation in patients with bone metastases. A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as bone metastases, radiotherapy and palliative care. The resulting articles were sorted for inclusion for palliative external beam radiation retreatment response rate data. The literature search produced 2164 references and 15 articles were included in the final selection. Complete, partial and overall response rates were calculated to be 20%, 50% and 68%, respectively. Information on treatment toxicities was scarce. The efficacy of re-irradiation is comparable to initial radiation treatment. However, aspects of re-irradiation treatment including dose fractionation, related adverse events and toxicities require further corroboration.