External beam radiation dose escalation for high grade glioma.

BACKGROUND: This is an updated version of the original Cochrane Review published in Issue 8, 2016. High grade glioma (HGG) is a rapidly growing brain tumour in the supporting cells of the nervous system, with several subtypes such as glioblastoma (grade IV astrocytoma), anaplastic (grade III) astrocytoma and anaplastic (grade III) oligodendroglioma. Studies have investigated the best strategy to give radiation to people with HGG. Conventional fractionated radiotherapy involves giving a daily radiation dose (called a fraction) of 180 cGy to 200 cGy. Hypofractionated radiotherapy uses higher daily doses, which reduces the overall number of fractions and treatment time. Hyperfractionated radiotherapy which uses a lower daily dose with a greater number of fractions and multiple fractions per day to deliver a total dose at least equivalent to external beam daily conventionally fractionated radiotherapy in the same time frame. The aim is to reduce the potential for late toxicity. Accelerated radiotherapy (dose escalation) refers to the delivery of multiple fractions per day using daily doses of radiation consistent with external beam daily conventionally fractionated radiotherapy doses. The aim is to reduce the overall treatment time; typically, two or three fractions per day may be delivered with a six to eight hour gap between fractions. OBJECTIVES: To assess the effects of postoperative external beam radiation dose escalation in adults with HGG. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid and Embase Ovid to August 2019 for relevant randomised phase III trials. SELECTION CRITERIA: We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens: daily conventionally fractionated radiotherapy versus no radiotherapy; hypofractionated radiotherapy versus daily conventionally fractionated radiotherapy; hyperfractionated radiotherapy versus daily conventionally fractionated radiotherapy or accelerated radiotherapy versus daily conventionally fractionated radiotherapy. DATA COLLECTION AND ANALYSIS: The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Since the last version of this review, we identified no new relevant trials for inclusion. We included 11 randomised controlled trials (RCTs) with 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for people with HGG receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 favouring postoperative radiotherapy (95% confidence interval (CI) 1.58 to 2.55; P < 0.00001; moderate-certainty evidence). Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17; P = 0.63; very low-certainty evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one participant in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data. Overall survival was similar between hypofractionated and conventional radiotherapy in the subset of two trials (293 participants) which included participants aged 60 years and older with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46; P = 0.21; high-certainty evidence). There were two trials which compared hyperfractionated radiotherapy versus conventional radiation and one trial which compared accelerated radiotherapy versus conventional radiation. However, the results could not be pooled. The conventionally fractionated radiotherapy regimens were 4500 cGy to 6000 cGy given in 180 cGy to 200 cGy daily fractions, over five to six weeks. All trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher. The risk of selection bias was generally low among these RCTs. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life. AUTHORS' CONCLUSIONS: Postoperative conventional daily radiotherapy probably improves survival for adults with good performance status and HGG compared to no postoperative radiotherapy. Hypofractionated radiotherapy has similar efficacy for survival compared to conventional radiotherapy, particularly for individuals aged 60 years and older with glioblastoma. There are insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy). There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These HGG individuals with poor prognosis have generally been excluded from randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these people with poor prognosis. Since the last version of this review, we found no new relevant studies. The search identified three new trials, but all were excluded as none had a conventionally fractionated radiotherapy arm.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

BACKGROUND: This is an update to the review published in the Cochrane Library (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will develop brain metastases during the course of their illness. The burden of brain metastases impacts quality and length of survival. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone or in combination with other therapies to adults with newly diagnosed multiple brain metastases. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National Cancer Institute Physicians Data Query for ongoing trials. SELECTION CRITERIA: We included phase III randomised controlled trials (RCTs) comparing WBRT versus other treatments for adults with newly diagnosed multiple brain metastases. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted information in accordance with Cochrane methods. MAIN RESULTS: We added 10 RCTs to this updated review. The review now includes 54 published trials (45 fully published reports, four abstracts, and five subsets of data from previously published RCTs) involving 11,898 participants.Lower biological WBRT doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty evidence) in favour of control. The HR for neurological function improvement (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in favour of control fractionation.Higher biological WBRT doses versus controlThe HR for OS with higher biological WBRT doses as compared with control (3000 cGy in 10 daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate-certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P = 0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to 1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence) favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to 3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P < 0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials reported worse neurocognitive outcomes and one trial reported worse quality of life outcomes when WBRT was added to radiosurgery.We could not pool data from trials related to chemotherapy, optimal supportive care (OSC), molecular targeted agents, neurocognitive protective agents, and hippocampal sparing WBRT. However, one trial reported no differences in quality-adjusted life-years for selected participants with brain metastases from non-small-cell lung cancer randomised to OSC and WBRT versus OSC alone. AUTHORS' CONCLUSIONS: None of the trials with altered higher biological WBRT dose-fractionation schemes reported benefit for OS, NFI, or symptom control compared with standard care. However, OS and NFI were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules.The addition of WBRT to radiosurgery improved local and distant brain control in selected people with brain metastases, but data show worse neurocognitive outcomes and no differences in OS.Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in OS when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or molecular targeted agents in conjunction with WBRT remains experimental.Further trials are needed to evaluate the use of neurocognitive protective agents and hippocampal sparing with WBRT. As well, future trials should examine homogeneous participants with brain metastases with focus on prognostic features and molecular markers.

External beam radiation dose escalation for high grade glioma.

BACKGROUND: The incidence of high grade glioma (HGG) is approximately 5 per 100,000 person-years in Europe and North America. OBJECTIVES: To assess the effects of postoperative external beam radiation dose escalation in adults with HGG. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE (1977 to October 2015) and Embase (1980 to end October 2015) for relevant randomised phase III trials. SELECTION CRITERIA: We included adults with a pathological diagnosis of HGG randomised to the following external beam radiation regimens.1. Daily conventionally fractionated radiation therapy versus no radiation therapy.2. Hypofractionated radiation therapy versus daily conventionally fractionated radiation therapy.3. Hyperfractionated radiation therapy versus daily conventionally fractionated radiation therapy.4. Accelerated radiation therapy versus daily conventionally fractionated radiation therapy. DATA COLLECTION AND ANALYSIS: The primary outcomes were overall survival and adverse effects. The secondary outcomes were progression-free survival and quality of life. We used the standard methodological procedures expected by Cochrane. We used the GRADE approach, as outlined by Cochrane, to interpret the overall quality of the evidence from included studies. MAIN RESULTS: We included 11 randomised controlled trials (RCTs) with a total of 2062 participants and 1537 in the relevant arms for this review. There was an overall survival benefit for HGG participants receiving postoperative radiotherapy compared to the participants receiving postoperative supportive care. For the four pooled RCTs (397 participants), the overall hazard ratio (HR) for survival was 2.01 (95% confidence interval (CI) 1.58 to 2.55, P < 0.00001), moderate GRADE quality evidence favouring postoperative radiotherapy. Although these trials may not have completely reported adverse effects, they did not note any significant toxicity attributable to radiation. Progression free survival and quality of life could not be pooled due to lack of data.Overall survival was similar between hypofractionated versus conventional radiotherapy in five trials (943 participants), where the HR was 0.95 (95% CI 0.78 to 1.17, P = 0.63), very low GRADE quality evidence. The trials reported that hypofractionated and conventional radiotherapy were well tolerated with mild acute adverse effects. These trials only reported one patient in the hypofractionated arm developing symptomatic radiation necrosis that required surgery. Progression free survival and quality of life could not be pooled due to the lack of data.Overall survival was also similar between hypofractionated versus conventional radiotherapy in the subset of two trials (293 participants) which included 60 years and older participants with glioblastoma. For this category, the HR was 1.16 (95% CI 0.92 to 1.46, P = 0.21), high GRADE quality evidence.There were two trials which compared hyperfractionated radiation therapy versus conventional radiation and one trial which compared accelerated radiation therapy versus conventional radiation. However, the results could not be pooled.The conventionally fractionated radiation therapy regimens were 4500 to 6000 cGy given in 180 to 200 cGy daily fractions, over 5 to 6 weeks.All these trials generally included participants with World Health Organization (WHO) performance status from 0 to 2 and Karnofsky performance status of 50 and higher.The risk of selection bias was generally low among these randomized trials. The number of participants lost to follow-up for the outcome of overall survival was low. Attrition, performance, detection and reporting bias for the outcome of overall survival was low. There was unclear attrition, performance, detection and reporting bias relating to the outcomes of adverse effects, progression free survival and quality of life. AUTHORS' CONCLUSIONS: Postoperative conventional daily radiotherapy improves survival for adults with good performance status and HGG as compared to no postoperative radiotherapy.Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.There is insufficient data regarding hyperfractionation versus conventionally fractionated radiation (without chemotherapy) and for accelerated radiation versus conventionally fractionated radiation (without chemotherapy).There are HGG subsets who have poor prognosis even with treatment (e.g. glioblastoma histology, older age and poor performance status). These poor prognosis HGG individuals have generally been excluded from the randomised trials based on poor performance status. No randomised trial has compared comfort measures or best supportive care with an active intervention using radiotherapy or chemotherapy in these poor prognosis patients.

Unanticipated Radiation Replanning for Stage III Non-small Cell Lung Cancer.

Purpose: The purpose of this study was to identify factors associated with unanticipated radiation therapy (RT) replanning in stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients from a single institution with newly diagnosed stage III NSCLC treated with radical RT from January 1, 2016, to December 31, 2019, were retrospectively analyzed. The frequency and reasons for replanning were determined. Logistic regression analysis was used to identify factors associated with replanning. Results: Of 144 patients included in this study, 11% (n = 16) required replanning after the start of RT. The reason for replanning in these 16 patients was changes in the target detected by cone beam computed tomography (shift in 10 patients, shrinkage in 5 patients, and growth in 1 patient). Larger planning target volume (primary and nodal) was statistically predictive of replanning (odds ratio, 2.5; 95% CI, 1.2-5.4; P = .02). The actuarial median overall survival was 33.3 months (95% CI, 10.3-43.9) for the 16 patients who were replanned and 36.3 months (95% CI, 27.4-66.5) for the remaining 128 patients (P = .96). The median time to local recurrence was 25.0 months (95% CI, 10.3-41.3) for those patients who underwent replanning, which was similar to those patients who did not undergo replanning (19.5 months; 95% CI, 11.8-23.2; P = .28). Conclusions: In this study, 11% of patients treated with radical RT for NSCLC required replanning due to changes in the target detected by cone beam computed tomography. A larger planning target volume predicts a higher likelihood of requiring adaptive RT. Overall survival and local control were similar between patients who were replanned compared with those who were not replanned.

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators.

PURPOSE: Surface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALS: Planning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3-5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTS: Ten patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7-40.6), mean CTV D0.1cc 49.2 Gy (range 45.6-53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0-1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONS: SMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

Volume specific response criteria for brain metastases following salvage stereotactic radiosurgery and associated predictors of response.

BACKGROUND: We aimed to derive three-dimensional volume-based (V(3D)) response criteria that approximate those based on Response Evaluation Criteria in Solid Tumours (RECIST) in patients with brain metastases (BM) treated with salvage stereotactic radiosurgery (SRS). MATERIAL AND METHODS: Seventy patients with 178 BM were treated with SRS. Each BM was characterised at baseline and at each follow-up MRI according to its widest diameter and V(3D) using ITK-SNAP image segmentation software. RESULTS: The median tumour diameter was 1.2 cm (range, 0.2-4.5 cm) and V(3D) was 0.73 cm(3) (range, 0.01-22.7 cm(3)). The V(3D) percent changes that best matched RECIST response criteria were: an increase of ≥71.5% for progressive disease, a ≥58.5% decrease for partial response and a <58.5% decrease or increase of <71.5% for stable disease (k =0.85). A baseline diameter >3.0 cm (p =0.006) and a V(3D) >6.0 cm(3) (p =0.043) predicted for local failure, and a baseline cumulative V(3D) of >3.0 cm(3) (p =0.02) was adversely prognostic for survival. CONCLUSIONS: We define 3D volume specific criteria to base response upon for brain metastases treated with salvage SRS. Tumours with a V(3D) of greater than 6 cm(3) are at a higher risk of local failure.

Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases.

BACKGROUND: Brain metastases represent a significant healthcare problem. It is estimated that 20% to 40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness. The burden of brain metastases impacts on quality and length of survival. Presenting symptoms include headache (49%), focal weakness (30%), mental disturbances (32%), gait ataxia (21%), seizures (18%), speech difficulty (12%), visual disturbance (6%), sensory disturbance (6%) and limb ataxia (6%).Brain metastases may spread from any primary site. The most common primary site is the lung, followed by the breast then gastrointestinal sites. Eighty-five per cent of brain metastases are found in the cerebral hemispheres, 10% to 15% in the cerebellum and 1% to 3% in the brainstem. Brain radiotherapy is used to treat cancer participants who have brain metastases from various primary malignancies.This is an update to the original review published in Issue 3, 2006. OBJECTIVES: To assess the effectiveness and adverse effects of whole brain radiotherapy (WBRT) in adult participants with multiple metastases to the brain. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2011), MEDLINE and EMBASE to July 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing WBRT either alone or with other treatments in adults with newly diagnosed multiple metastases to the brain from any primary cancer. Trials of prophylactic WBRT were excluded as well as trials that dealt with surgery or WBRT, or both, for the treatment of single brain metastasis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and abstracted information. Adverse effects information was also collected from the trials. MAIN RESULTS: Nine RCTs involving 1420 participants were added in this updated review. This updated review now includes a total of 39 trials involving 10,835 participants.Eight published reports (nine RCTs) showed no benefit of altered dose-fractionation schedules as compared to the control fractionation (3000 cGy in 10 fractions daily) of WBRT for overall survival. These studies also showed no improvement in symptom control nor neurologic improvement among the different dose-fractionation schemes as compared to 3000 cGy in 10 daily fractions of WBRT. This updated review includes two trials comparing 4000 cGy in 20 fractions given twice daily versus 2000 cGy in 4 or 5 daily fractions. Overall, there was no survival advantage (hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.89 to 1.56, P = 0.25) with the use of 4000 cGy in 20 fractions given twice daily compared to 2000 cGy in 4 or 5 daily fractions.The addition of radiosensitizers in six RCTs did not confer additional benefit to WBRT in either the overall survival times (HR 1.08, 95% CI 0.98 to 1.18, P = 0.11) or brain tumour response rates (HR 0.87, 95% CI 0.60 to 1.26, P = 0.46).Two RCTs found no benefit in overall survival (HR 0.61, 95% CI 0.27 to 1.39, P = 0.24) with the use of WBRT and radiosurgery boost as compared to WBRT alone for selected participants with multiple brain metastases (up to four brain metastases). Overall, there was a statistically significant improvement in local brain control (HR 0.35, 95% CI 0.20 to 0.61, P = 0.0003) favouring the WBRT and radiosurgery boost arm. Only one trial of radiosurgery boost with WBRT reported an improved Karnofsky performance score outcome and improved ability to reduce the dexamethasone dose.In this updated review, a total of three RCTs reported on selected patients (with up to three or four brain metastases) treated with radiosurgery alone versus WBRT and radiosurgery. Based on two trials, there was no difference in overall survival (HR 0.98, 95% CI 0.71 to 1.35, P = 0.88). The addition of WBRT when added to radiosurgery significantly improved locally treated brain metasatases control (HR 2.61, 95% CI 1.68 to 4.06, P < 0.0001) and distant brain control (HR 2.15, 95% CI 1.55 to 2.99, P < 0.00001). On the other hand, one trial concluded that patients treated with WBRT and radiosurgery boost were significantly more likely to show a decline in learning and memory function as compared to those treated with radiosurgery alone.One RCT examined the use of WBRT and prednisone versus prednisone alone and produced inconclusive results. AUTHORS' CONCLUSIONS: None of the RCTs with altered WBRT dose-fractionation schemes as compared to standard (3000 cGy in 10 daily fractions or 2000 cGy in 4 or 5 daily fractions) found a benefit in terms of overall survival, neurologic function, or symptom control.The use of radiosensitizers or chemotherapy in conjunction with WBRT remains experimental.Radiosurgery boost with WBRT may improve local disease control in selected participants as compared to WBRT alone, although survival remains unchanged for participants with multiple brain metastases.This updated review now includes a total of three RCTs examining the use of radiosurgery alone versus WBRT and radiosurgery. The addition of WBRT to radiosurgery improves local and distant brain control but there is no difference in overall survival. Patients treated with radiosurgery alone were found to have better neurocognitive outcomes in one trial as compared to patients treated with WBRT and radiosurgery.The benefit of WBRT as compared to supportive care alone has not been studied in RCTs. It may be that supportive care alone, without WBRT, is appropriate for some participants, particularly those with advanced disease and poor performance status.

Glioblastoma: patterns of recurrence and efficacy of salvage treatments.

BACKGROUND: It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival. METHODS: We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival. RESULTS: 58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61). CONCLUSION: The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

Pseudoprogression following chemoradiotherapy for glioblastoma multiforme.

PURPOSE: Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis. MATERIALS/METHODS: All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups. RESULTS: Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p = 0.0286). CONCLUSIONS: Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

Multiple bone metastases: what the palliative care specialist should know about the potential, limitations and practical aspects of radiation therapy.

Bone metastases represent a significant health care problem in the cancer population. The most common symptom for bone metastases is pain. Bone metastases may also cause pathologic fracture, spinal cord compression, cauda equina compression and serum calcium disorders. This review article summarizes the epidemiology, diagnostic modalities, role for radiation, and future directions as it pertains to bone metastases. Radiotherapy is an effective and standard modality for the treatment of painful complicated and uncomplicated bony metastases. Further strategies are needed to optimize pain relief, quality of life and survival in the bone metastases cancer population.

Radiation for below the knee skin cancers: a single institution experience.

Background: Historically, radiation to skin cancers for the lower legs has been avoided due to the perceived increased risk of radiation toxicity (poor wound healing, radiation necrosis). However, there is a paucity of published data regarding this perceived risk.Purpose: The objective was to review the risk of poor wound healing/radiation necrosis occurring post radiation and to determine rates of complete response (CR), partial response (PR), and progressive disease after radiation therapyMaterials and methods: A retrospective review of patients treated with radiation for skin cancer below the knee was undertaken from January 1, 2013 to May 31, 2018.Results: A total of 25 patients with 39 below the knee skin sites were treated with radiation. Mean follow-up time was 19 months (range 3 months-7.2 years). Crude CR, PR and progression rates for the treated lesions were 65%, 19%, and 16% respectively. Four out of 23 (17%) patients developed Grade 3 skin toxicity. There were no grades 4 or 5 toxicities.Conclusions: For patients not eligible for surgery, radiation therapy is an option with a moderate chance of complete response (65%) and a 17% risk of poor wound healing/radiation necrosis.

Stereotactic Body Radiation Therapy for Extracranial Oligometastatic Non-small-cell Lung Cancer: A Systematic Review.

Stereotactic body radiation therapy (SBRT) has emerged as a treatment modality for selected patients with oligometastatic non-small-cell lung cancer (NSCLC). The objectives of this systematic review were to explore the benefits and risks of SBRT for extracranial oligometastatic NSCLC. The MEDLINE, Embase, PubMed, and CENTRAL databases were searched for relevant articles from January 1, 2000 to July 23, 2019. Fully published phase III or phase II trials of any sample size were included. Retrospective series published in manuscript form with at least 50 patients were also included. Four prospective phase II randomized trials (total, 188 participants), 4 prospective non-randomized studies (total, 140 participants), and eleven retrospective studies (total, 1288 participants) were included in this systematic review. A variety of dose fractionation schemes were used. The median overall survival (OS) ranged from 13.5 to 55 months. Progression-free survival (PFS) ranged from 4.4 to 14.7 months. Quality of life outcomes were reported in 2 studies. None of the studies reported symptom control outcomes. There are no fully completed phase III randomized trials that clarify the risks and benefits of SBRT for oligometastatic NSCLC. Higher PFS and OS with SBRT were reported in 4 phase II randomized studies. The results from mature phase III randomized data regarding whether SBRT for oligometastatic NSCLC benefits patients in terms of OS, PFS, quality of life, and symptom control are needed.

Should dexamethasone be standard in the prophylaxis of pain flare after palliative radiotherapy for bone metastases?-a debate.

Pain flare is a well-recognized side-effect of palliative radiotherapy for the treatment of painful bone metastases, with recent randomized data showing incidence rates up to 35%. The impact of pain flare has been associated with worsening immobility, anxiety, depression and quality of life. The use of dexamethasone has recently been supported as an effective option in reducing radiation-induced pain flare based on the NCIC Clinical Trials Group (NCIC CTG) Symptom Control 23 (SC.23) randomized double-blind placebo-controlled trial. Despite this, conflicting opinions exist, and standard clinical use of dexamethasone to prevent pain flare continues to be debated among clinicians. Given this controversy, two sides of the debate are presented. Although consensus has not been achieved, the choice to use dexamethasone in the prophylactic setting to reduce pain flare incidence should be a shared decision between the oncologist and patient. Factors including symptom burden, comorbidities, performance status, quality of life and radiation dose and fractionation should be taken into account on an individualized level.

Quality of life in patients with brain metastases treated with a palliative course of whole-brain radiotherapy.

BACKGROUND: The primary objective of this study was to assess whether there was an improvement in quality of life for patients with brain metastases as measured 1 and 2 months after a course of whole-brain radiotherapy. The secondary objective was to assess the level of agreement between patient and proxy quality of life scores. METHODS AND MATERIALS: Sixty patients with brain metastases and their proxy completed the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire independently. Proxies were given instructions to answer from the patient's perspective. Quality-of-life assessments were conducted at baseline, 1 month, and 2 months after completion of whole-brain radiotherapy. Paired t tests with Bonferroni adjustment for multiple comparisons were calculated to detect significant differences in global quality-of-life scores. Lin's concordance correlation coefficient measured agreement between patient and proxy quality-of-life ratings. RESULTS: No significant difference was detected in overall quality of life after whole-brain radiotherapy. At 2 months after whole-brain radiotherapy, there was a trend toward worsening general and brain specific quality-of-life scores. There was poor concordance between patients and their proxies for all quality-of-life domains at baseline. CONCLUSION: At 2 months after whole-brain radiotherapy, there was a trend toward worsening general and brain specific quality-of-life scores. Proxy rating of patients' quality of life showed poor concordance at baseline.

Stereotactic radiosurgery for vestibular schwannoma: International Stereotactic Radiosurgery Society (ISRS) Practice Guideline.

OBJECTIVES: The aim of this systematic review was to develop International Stereotactic Radiosurgery Society (ISRS) consensus guideline statements for vestibular schwannoma. METHODS: A systematic review of the literature was performed up to April 2015. RESULTS: A total of 55 full-text articles were included in the analysis. All studies were retrospective, except for 2 prospective quality of life studies. Five-year tumour control rates with Gamma Knife radiosurgery (RS), single fraction linac RS, or fractionated (either hypofractionated or conventional fractionation) stereotactic radiation therapy (FSRT) were similar at 81-100%. The single fraction RS series (linac or Gamma Knife) with tumour marginal doses between 12 and 14 Gy revealed 5-year tumour control rates of 90-99%, hearing preservation rates of 41-79%, facial nerve preservation rates of 95-100% and trigeminal preservation rates of 79-99%.There were 6 non-randomized studies comparing single fraction RS versus FSRT. There was no statistically significant difference in tumour control; HR=1.66 (95% CI 0.81, 3.42), p =0.17, facial nerve function; HR = 0.67 (95% CI 0.30, 1.49), p =0.33, trigeminal nerve function; HR = 0.80 (95% CI 0.41, 1.56), p =0.51, and hearing preservation; HR = 1.10 (95% CI 0.72, 1.68), p =0.65 comparing single fraction RS with FSRT.Nine quality of life reports yielded conflicting results as to which modality (surgery, observation, or radiation) was associated with better quality of life outcomes. CONCLUSIONS: There are no randomized trials to help guide management of patients with vestibular schwannoma. Within the limitations of the retrospective series, a number of consensus statements were made.

Hospitalizations in elderly glioblastoma patients.

BACKGROUND: Elderly glioblastoma (GB) patients are at risk of hospitalizations due to the morbidity of the disease and possible treatment toxicity. METHODS: In this observational cohort study, 255 newly diagnosed GB patients age 65 years and older were included. Survival, emergency room visits and admissions to an acute care hospital were determined. Mean and median total health care costs were calculated. Risk factors for Emergency room visits and acute care hospital admissions were determined. RESULTS: Median overall survival was 6 months. The majority of patients (68%) had at least one visit to the emergency department and 77% had at least one admission to acute care. The mean and median total costs (hospital, ambulatory, physician billing, other health care costs) per patient were $162,479.78 (CAN) and $125,511.00 (CAN), respectively. Treatment with radiation or treatment with radio-chemotherapy was associated with a relative risk (RR) of 2.31 (95% CI: 1.44-3.7; P=0.0005) and 2.19 (95% CI: 1.28-3.74; P=0.004), respectively for emergency department visits as compared to patients who were managed with comfort measures only. Patients with a baseline ECOG 0 had a RR of 1.71 (95% CI: 1.06-2.77; P=0.0289) and patients with baseline ECOG 1 had a RR of 1.49 (0.98-2.26; P=0.0623) for hospital admission as compared to patients with ECOG 4. CONCLUSIONS: A large proportion of elderly GB patients (particularly those with good baseline performance status who underwent active treatment) presented to the emergency department and had at least one admission to acute care.

Radiosurgical treatment for rolandic arteriovenous malformations.

OBJECT: The authors reviewed the radiosurgical outcomes in patients with arteriovenous malformations (AVMs) located in the rolandic area, including the primary motor and sensory gyri. METHODS: The study population consisted of 38 patients with rolandic-area AVMs who underwent linear accelerator radiosurgery at the University of Toronto between 1989 and 2000. Obliteration rate, risk of hemorrhage during the latency period, radiation-induced complications, seizure control, and functional status were evaluated. Patients were also divided into two subgroups according to AVM volume (< 3 cm3 and > or = 3 cm3). Patients were followed up for a median of 42.4 months (range 30-103 months), and the median age of the patients was 40 years (range 12-67 years). The median AVM volume was 8.1 cm3 (range 0.32-21, mean 8.32 cm3), and the median dose at the tumor margin was 15 Gy (range 15-22, mean 16.8 Gy). The risk of hemorrhage after radiosurgery was 5.3% for the 1st year, 2.6% for the 2nd, and 0% for the 3rd. Two patients (5.3%) sustained adverse effects related to radiation for more than 6 months. Complete nidus obliteration after a single radiosurgical treatment was achieved in 23 patients (60.5%). The obliteration rate for AVMs smaller than 3 cm3 was 83.3% (10 of 12) and that for AVMs larger than or equal to 3 cm3 was 50% (13 of 26). Among the patients who had seizures as the initial presentation, 51.8% were free of seizures after radiosurgery and the seizure pattern improved in 40.7% during the 3rd and last year of follow up. Overall, excellent results (obliteration and no new or worsening neurological deficit) can be achieved in approximately 60% of patients. This percentage varies according to the AVM size and can reach 83% in patients with AVMs smaller than 3 cm3. CONCLUSIONS: Radiosurgery is a safe and effective treatment for people with rolandic AVMs. The low rate of morbidity associated with radiosurgery, compared with other treatments, indicates that this method may be the first choice for patients with AVMs located in this area.

Radiosurgical retreatment for brain arteriovenous malformation.

OBJECTIVE: To analyze our experience with a second radiosurgical treatment for brain arteriovenous malformations (BAVMs) after an unsuccessful first radiosurgical treatment. METHODS: Between 1993 and 2000, 242 patients were treated by the Toronto Sunnybrook Regional Cancer Center using a LINAC system. Fifteen of these patients required a second radiosurgical intervention due to the failure of the first procedure. Data was collected on baseline patient characteristics, BAVM features, radiosurgery treatment plan and outcomes. Brain arteriovenous malformation obliteration was determined by follow-up MRI and angiography and the obliteration prediction index (OPI) calculated according to a previously established formula. RESULTS: The median interval between the first and second treatment was 46 months (range 39-109). The median follow-up after the second procedure was 39 months (range 26 to 72). The mean BAVM volume before the first treatment was 8.9cm3 (range 0.3-21) and before the second treatment was 3.6cm3 (range 0.2-11.6). The mean marginal dose during the first treatment was 18Gy (range 12-25) and during the second treatment was 16Gy (range 12-20). After the second treatment, nine patients had obliteration of their BAVM confirmed by angiography and one patient had obliteration confirmed by MRI, resulting in an obliteration rate of 66.6%, which is very comparable to that predicted by the OPI (65%). After the second treatment two patients had a radiation-induced complication (13.3%). CONCLUSION: Retreatment of BAVM using a second radiosurgery procedure is a safe and effective option that offers the same rate of success as the initial radiosurgery and an acceptable risk of radiation-induced complication.