PSMA Expression Correlates with Improved Overall Survival and VEGF Expression in Glioblastoma.

BACKGROUND: Glioblastomas are the most common and fatal primary brain malignancy in adults. There is a growing interest in identifying the molecular mechanisms of these tumors to develop novel treatments. Glioblastoma neo-angiogenesis is driven by VEGF, and another potential molecule linked to angiogenesis is PSMA. Our study suggests the potential for an association between PSMA and VEGF expression in glioblastoma neo-vasculature. METHODS: Archived IDH1/2 wild-type glioblastomas were accessed; demographic and clinical outcomes were recorded. PSMA and VEGF expression by IHC were examined. Patients were dichotomized into PSMA expression high (3+) and low (0-2+) groups. The association between PSMA and VEGF expression was evaluated using Chi2 analysis. OS in PSMA high and low expression groups were compared using multi-linear regression. RESULTS: In total, 247 patients with IDH1/2 wild-type glioblastoma with archival tumor samples (between 2009-2014) were examined. PSMA expression correlated positively with VEGF expression (p = 0.01). We detected a significant difference in median OS between PSMA vascular endothelial expression high and low groups-16.1 and 10.8 months, respectively (p = 0.02). CONCLUSION: We found a potential positive correlation between PSMA and VEGF expression. Secondly, we showed a potential positive correlation between PSMA expression and overall survival.

Implications of Concurrent IDH1 and IDH2 Mutations on Survival in Glioma-A Case Report and Systematic Review.

Both IDH1 (isocitrate dehydrogenase 1) and IDH2 (isocitrate dehydrogenase 2) mutations play a vital role in the development of gliomas through disruption of normal cellular metabolic processes. Here we describe a case of a patient with an IDH-mutant astrocytoma, in which both IDH1 and IDH2 mutations were detected within the same tumour. The patient remains disease-free, nine and a half years after her initial diagnosis. Interrogation of cancer genomic databases and a systematic review was undertaken, demonstrating the rarity of the co-occurrence of IDH1 and IDH2 mutations in a variety of cancer types, and in glioma specifically. Due to the favourable outcome observed in this patient, the potential effect of concurrent IDH1 and IDH2 mutations on survival was also investigated.

Volumetric Response of Limited Brain Metastatic Disease to Focal Hypofractionated Radiation Therapy.

Background: This is a retrospective study aimed at assessing the volumetric response, morbidity and failure rates of hypofractionated radiation therapy (HFRT) for definitive focal management of limited brain metastasis. Methods: Patients managed with HFRT for unresected limited metastatic (≤10 lesions) brain disease were entered into an ethics-approved database. Included patients had been deemed unsuitable for surgical resection, and lesions managed with prior radiation therapy were excluded. HFRT was delivered using IMRT or VMAT with 25 Gy or 30 Gy in five fractions. Individual lesions had volumetric assessment performed at three timepoints. The primary endpoint was the change of volume from baseline (GTV0) to one month post-HFRT (GTV1) and to seven months post-HFRT (GTV7). Secondary endpoints were local failure, survival and rates of radiation necrosis. Results: One hundred and twenty-four patients with 233 lesions were managed with HFRT. Median follow-up was 23.5 months with 32 (25.8%) patients alive at censure. Median overall survival was 7.3 months with 36.3% survival at 12 months. Superior survival was predicted by smaller GTV0 (p = 0.003) and increased percentage of volumetric response (p < 0.001). Systemic therapy was delivered to 81.5% of patients. At one month post-HFRT, 206 metastases (88.4%) were available for assessment and at seven months post-HFRT, 118 metastases (50.6%) were available. Median metastasis volume at GTV0 was 1.6 cm3 (range: 0.1-19.1). At GTV1 and GTV7, this reduced to 0.7 cm3 (p < 0.001) and 0.3 cm3 (p < 0.001), respectively, correlating to percentage reductions of 54.9% and 83.3%. No significant predictors of volumetric response following HFRT were identified. Local failure was identified in 4.3% of lesions and radiation necrosis in 3.9%. Conclusion: HFRT is an effective therapy for limited metastatic disease in the brain to maximise initial volumetric response whilst minimising toxicity.

Redo craniotomy or bevacizumab for symptomatic steroid-refractory true or pseudoprogression following IMRT for glioblastoma.

BACKGROUND: There is minimal evidence to support decision making for symptomatic steroid-refractory pseudoprogression or true progression occurring after intensity-modulated radiation therapy (IMRT) for glioblastoma (GBM). This study audited the survival outcome of patients managed with redo craniotomy (RedoSx) or bevacizumab (BEV) for steroid-refractory mass effect after IMRT for GBM. METHODS: Patients with GBM managed between 2008 and 2019 with the EORTC-NCIC Protocol were entered into a prospective database. Patients with symptomatic steroid-refractory mass effect within 6 months of IMRT managed with either RedoSx or BEV were identified for analysis. For the primary endpoint of median overall survival (OS) postintervention, outcome was analyzed in regards to potential prognostic factors, and differences between groups were assessed by log-rank analyses. RESULTS: Of the 399 patients managed with the EORTC-NCIC Protocol, 78 required an intervention within 6 months of IMRT completion for either true or pseudoprogression (49 with RedoSx and 29 with BEV). Subsequently, 20 of the 43 patients managed with RedoSx when BEV was clinically available, required salvage with BEV within 6 months after RedoSx. Median OS postintervention was 8.7 months (95% CI: 7.84-11.61) for the total group; and 8.7 months (95% CI: 6.8-13.1) for RedoSx and 9.4 months (95% CI: 7.8-13.6) for BEV (P = .38). Subsequent use of BEV in RedoSx patients was not associated with improved survival compared with RedoSx alone (P = .10). Age, time from IMRT, and ECOG performance status were not associated with OS. In the RedoSx patients, immunohistochemical features such as Ki-67% reduction correlated with survival. The presence of pure necrosis and residual tumor cells only had improved survival compared with the presence of gross tumor (P < .001). CONCLUSIONS: At time of symptomatic steroid-refractory true or pseudoprogression following IMRT for GBM, BEV was equivalent to RedoSx in terms of OS. Pseudoprogression with residual cells at RedoSx was not associated with worse outcome compared to pure necrosis.

Reflecting on survivorship outcomes to aid initial decision making in patients treated for IDH-mutated anaplastic glioma.

BACKGROUND: Patients with anaplastic glioma (AG) harboring an isocitrate dehydrogenase mutation have potential durable survival after intensity-modulated radiotherapy (IMRT) and chemotherapy. Understanding long-term functioning, and the factors that have an impact on later effects, is important for decision making. METHODS: Consecutive patients with AG who received IMRT were reviewed with regard to 6 survivorship domains, including Eastern Cooperative Oncology Group (ECOG) performance status, Medical Research Council (MRC) neurological status, late toxicity, comorbidity, functional status (employment/driving), and psychosocial events. Assessments were performed at baseline before RT; at month +6; and at years +1, +3, and +5 after RT. The primary endpoints were ECOG at year +3 and employment at year +3. RESULTS: A total of 146 patients were included, with a median follow-up of 5.1 years. The 6-year overall survival rate was 78.7% (95% CI, 71.1%-87.0%). Baseline ECOG performance status was 0 to 1 in 82.2% of patients but improved at year +1 (95.7%) and year +3 (97.2%). Employment rates at year +3 and year +5 were 70.1% and 76.5%, respectively, compared with 61.6% at baseline. Worse ECOG performance status at year +3 was related to the anaplastic astrocytoma subtype (P = .001), delayed RT (P = .081), multiple craniotomies performed before RT (P = .002), worse ECOG performance status before RT (P < .001), worse MRC neurological status before RT (P < .001), seizures (P = .038), neurocognitive disturbance (P < .001), and the presence of recurrent disease (P = .004). Absent or impaired employment at year +3 was found to be related to older age (P = .007), delayed timing of RT (P = .023), multiple craniotomies prior to RT (P = .005), worse ECOG performance status before RT (P < .001), worse MRC neurological status before RT (P < .001), and neurocognitive disturbance (P < .001). CONCLUSIONS: Patients with AG with an isocitrate dehydrogenase mutation have the potential for prolonged survival. Functional status appears to be good in patients who are free of disease progression at 3 to 5 years after IMRT, with >95% of patients having high ECOG performance status and >75% being employed.

Survival improvements with adjuvant therapy in patients with glioblastoma.

BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log-rank comparisons. RESULTS: Two hundred and thirty-three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re-resection, and in addition to second-line chemotherapy, 86 patients had Bevacizumab including 26 with re-irradiation. Median survival was 17.0 months (95% CI: 15.4-18.6). On univariate evaluation, extent of resection (P = 0.001), age, ECOG performance status and recursive partitioning analysis class III were shown to significantly improve survival (P < 0.0001). The median survival for gross total resection, age <50 years, ECOG 0-1 and recursive partitioning analysis class III were 21, 27, 20 and 47 months, respectively. CONCLUSION: This study confirms the significant improvement in median survival in GBM that has occurred in recent years since introduction of the EORTC-NCIC protocol. Further improvements have occurred presumably related to subspecialized care, improved resection rates, sophisticated radiotherapy targeting and early systemic salvage therapies. However, the burden of the disease within the community remains high and the median survival improvements over time have plateaued.

Is advanced age a barrier to effective cancer treatment? The experience of nonagenarians receiving radiation therapy.

AIM: Decision-making about elderly patients is difficult due to the absence of clinical experience or evidence-based results to develop optimal treatment plans. This study aims to determine the tolerability and impact of radiation therapy (RT) when delivered to patients aged >89 years. METHODS: A retrospective review was conducted on all nonagenarian patients (defined as aged 90 years or over) managed with RT between 2005 and 2007. Patients' records were reviewed in regard to their characteristics, the presence of significant medical comorbidities, performance status, management intent, cancer diagnosis and RT modality. Outcome end-points were overall survival and the tolerability of RT (presence of grade 3 or 4 morbidity, hospital admission or treatment interruption). RESULTS: Between 2005 and 2007, 2762 new courses of RT were delivered to patients at the Northern Sydney Cancer Centre, of whom 55, or 2%, were nonagenarians. Median age at treatment was 92 years, with range 90-104 years. A total of 56% were managed with radical intent, 31% had significant comorbidities, 55% had non-skin primary tumors and 78% received linac-based treatment. The mean follow up for survivors was 19.8 months (10.2-41.8 months). RT was well tolerated, with 89% completing planned RT and only 18% requiring interruption. One patient was hospitalized due to RT toxicity. Median survival post-RT was 13.0 months, with 56% of patients alive at 12 months. Survival duration was associated with radical management intent (P= 0.001), cutaneous primary site (P= 0.001) and female gender (P= 0.043). CONCLUSION: Nonagenarian patients receiving treatment had satisfactory tolerability and achieved expected survival rates post-RT.

Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and a D2 node dissection for gastric adenocarcinoma.

PURPOSE: Intergroup 0116 (INT-0116) established adjuvant chemoradiation as the standard of care for resected high-risk adenocarcinoma of the stomach in the United States. However, adjuvant chemoradiation remains controversial in many parts of Asia and Europe, where patients tend to undergo a more thorough D2 dissection. In INT-0116, 90% of patients had a limited or inadequate node dissection (D0 or D1). Also, 17% of patients in the chemoradiation arm had to discontinue treatment because of toxicities. The objectives of this retrospective study are to report the clinical outcomes of a cohort of patients who were mostly treated with a D2 node dissection and received adjuvant chemoradiation as per INT-0116, and the toxicities of chemoradiation in the context of more aggressive surgery. METHODS: After the results of INT-0116 became apparent, we adopted an institutional policy whereby patients who would otherwise fit the inclusion criteria of INT-0116 received adjuvant chemoradiation. Between March 1999 and November 2004, 70 consecutive patients with pathologic stage T3, T4, or node-positive disease were treated according to the chemoradiation arm of INT-0116. Patients received intravenous 5-fluorouracil 425 mg/m and leucovorin 20 mg/m in cycles 1, 3, and 4. Concurrent chemoradiation was given in cycle 2 and consisted of bolus 5-fluorouracil and leucovorin and radiotherapy (45 Gy over 25 fractions in 5 weeks). All patients were operated on by dedicated Japan-trained Surgical Oncologists. RESULTS: Sixty-seven patients (96%) had a D2 nodal dissection. Sixty-five patients (93%) had negative pathologic margins (R0 resection) and 5 (7%) had microscopically involved margins (R1 resection). The median follow-up was 27 months (range, 10.1-60.3). The 3-year overall survival, disease-free survival, and local control were 60.6%, 54.1%, and 84.3%, respectively. Of the 30 patients who relapsed, 5 (17%) had isolated locoregional recurrences only. The National Cancer Institute--Common Terminology Criteria version 3.0 acute grade 3 or 4 gastrointestinal and hematological toxicity rates were 15.7% and 4.3%, respectively. Toxicities led to chemotherapy dose-reductions in 18 patients and dose-delay in 19 patients. Including chemotherapy dose-reductions and delays, 66 patients (94%) completed the entire chemoradiation regimen. There were no toxicity-related deaths. CONCLUSION: In our cohort of 70 patients who had a more thorough D2 node dissection, adjuvant chemoradiation was well tolerated with acceptable toxicities and reasonable tumor control.

Optimising radiation therapy techniques for tumours of the central nervous system.

INTRODUCTION: This study aims to assess the early tumour outcome and morbidity associated with radiation therapy (RT) in tumours of the central nervous system (CNS). MATERIALS AND METHODS: Patients receiving RT with radical intent were entered on a prospective database. Tumour types were categorised into glioma, base of skull, pituitary, germ cell or primitive neuroectodermal tumour (PNET) and other malignant CNS tumours. Study endpoints were overall survival and progression free survival. Acute and late toxicity endpoints included Common Terminology Criteria version 3.0 (CTC) grade 3 or 4 events, need for admission during RT and change in performance status at 12 months. RESULTS: One hundred and fifty-two patients with CNS tumours were managed with radical intent over the 4-year period. The median age was 49 years and 68.4% were Eastern Co-operative Group (ECOG) 0-1 performance status. The major pathology groups were glioma (59.9%) and base of skull tumours (17.1%). Gross total resection was performed in 28.3% only and RT was delayed after diagnosis until time of progression in 19.7%. For the 91 patients with glioma, the median survival and 2-year survival rate was 19.1 months and 44.1%, respectively. The 2-year survival rates for the subgroups of WHO Grade I or II, III and IV were 100%, 52% and 35%, respectively. For the non-glioma tumour groups, the relapse varied with pathology. Toxicity was minimal with only 3 acute and 3 late CTC grade 3 or 4 events occurring. Overall, 47 or 31% of patients required some inpatient hospitalisation during RT, although this was determined to have some causative relationship to RT in only 12 or 8% of patients. In the 12 months post-RT, performance status was stable or improved in 76.2% of patients, and most deterioration was associated with tumour relapse. CONCLUSIONS: RT for CNS tumours using modern techniques was well-tolerated with good tumour outcome and minimal morbidity.

Improved median survival for glioblastoma multiforme following introduction of adjuvant temozolomide chemotherapy.

INTRODUCTION: The use of adjuvant temozolomide (TMZ) in patients managed with surgery and adjuvant radiation therapy (RT) for glioblastoma multiforme (GBM) has been demonstrated to improve median and 2-year survival in a recent large international multicentre study. To confirm this result in routine clinical practice, an audit of the management and outcome of patients with GBM at The Cancer Institute Radiation Oncology was performed. MATERIALS AND METHODS: All patients with GBM managed radically at The Cancer Institute Radiation Oncology from May 2002 to 2006 were entered into a prospective database. Patient, tumour and treatment factors were analysed for association with the outcome of median survival (MS). Survival was calculated using the Kaplan-Meier technique and correlation was assessed using Cox proportional hazards regression. RESULTS: Forty-one patients with GBM were managed with radical intent over the 4- year period. The median age was 54 years and 66% were Eastern Cooperative Oncology Group (ECOG) 0-1 performance status. Macroscopic, subtotal and biopsy alone procedures were performed in 61%, 29% and 10% of patients, respectively. The median time from surgery to RT was 26 days. Adjuvant TMZ was used in 44% of patients (n = 18). The MS of the total group was 13.6 months, with a 24% 2-year overall survival. The use of TMZ was associated with improved MS (19.6 versus 12.8 months; P = 0.035) and improved 2-year survival (43% versus 0%). A requirement of dexamethasone dose greater than 4 mg at the end of RT (P = 0.012) was associated with worse survival, but there was no association of MS with age, ECOG, tumour size or extent of surgery. CONCLUSION: The median and 2-year survival outcomes are comparable to the results of the European Multicentre Study and justify the continued use of TMZ in routine clinical practice.

Improvements in quality of care resulting from a formal multidisciplinary tumour clinic in the management of high-grade glioma.

INTRODUCTION: There is increasing belief that a formal protocol-based multidisciplinary care model should be adopted as an optimal care model in oncology. However, there is minimal outcome evidence to demonstrate an improvement in patient care. The aim of this study was to compare clinical quality outcomes between patients with high-grade glioma managed at one hospital using a formal neuro-oncology multidisciplinary tumour clinic (MTC) and a second hospital with a traditional on-call referral pattern (non-MTC). MATERIALS AND METHODS: Patients with high-grade glioma managed radically with radiation therapy at 2 Singapore hospitals from May 2002 to May 2006 were entered into a prospective database. Patients were grouped into management via MTC or non-MTC. Four clinical quality indicators were chosen retrospectively to assess the variation in practice: a) Use of computed tomography (CT) or magnetic resonance (MR) imaging post-resection (POI) for assessment of residual disease; b) Commencement of radiation therapy (RT) within 28 days of surgery; c) Adjuvant chemotherapy use for glioblastoma multiforme (CTGBM) and d) Median survival. RESULTS: Sixty-seven patients were managed radically, with 47 by MTC and by 20 by non-MTC. MTC patients were more likely to have POI (P = 0.042), and CTGBM (P = 0.025). Although the RT start time was similar for the whole cohort (60% versus 45%: P = 0.296); for GBM patients, the RT start was earlier (63% vs 33% P = 0.024). The median survival for the MTC group was 18.7 months versus 11.9 months for the non-MTC group (P = 0.11). CONCLUSION: Clinical quality outcomes were significantly improved in patients with high-grade glioma managed in this neuro-oncology MTC.

The role of palliative radiation therapy in symptomatic locally advanced gastric cancer.

PURPOSE: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. METHODS AND MATERIALS: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at The Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). RESULTS: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. CONCLUSION: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

Efficacy of an integrated continuing medical education (CME) and quality improvement (QI) program on radiation oncologist (RO) clinical practice.

PURPOSE: There has been little radiation oncologist (RO)-specific research in continuing medical education (CME) or quality improvement (QI) program efficacy. Our aim was to evaluate a CME/QI program for changes in RO behavior, performance, and adherence to department protocols/studies over the first 12 months of the program. METHODS AND MATERIALS: The CME/QI program combined chart audit with feedback (C-AWF), simulation review AWF (SR-AWF), reminder checklists, and targeted CME tutorials. Between April 2003 and March 2004, management of 75 patients was evaluated by chart audit with feedback (C-AWF) and 178 patients via simulation review audit (SR-AWF) using a validated instrument. Scores were presented, and case management was discussed with individualized educational feedback. RO behavior and performance was compared over the first year of the program. RESULTS: Comparing the first and second 6 months, there was a significant improvement in mean behavior (12.7-13.6 of 14, p = 0.0005) and RO performance (7.6-7.9 of 8, p = 0.018) scores. Protocol/study adherence significantly improved from 90.3% to 96.6% (p = 0.005). A total of 50 actions were generated, including the identification of learning needs to direct CME tutorials, the systematic change of suboptimal RO practice, and the alteration of deficient management of 3% of patients audited during the program. CONCLUSION: An integrated CME/QI program combining C-AWF, SR-AWF, QI reminders, and targeted CME tutorials effectively improved targeted RO behavior and performance over a 12-month period. There was a corresponding increase in departmental protocol and study adherence.

External audit of clinical practice and medical decision making in a new Asian oncology center: results and implications for both developing and developed nations.

PURPOSE: The external audit of oncologist clinical practice is increasingly important because of the incorporation of audits into national maintenance of certification (MOC) programs. However, there are few reports of external audits of oncology practice or decision making. Our institution (The Cancer Institute, Singapore) was asked to externally audit an oncology department in a developing Asian nation, providing a unique opportunity to explore the feasibility of such a process. METHODS AND MATERIALS: We audited 100 randomly selected patients simulated for radiotherapy in 2003, using a previously reported audit instrument assessing clinical documentation/quality assurance and medical decision making. RESULTS: Clinical documentation/quality assurance, decision making, and overall performance criteria were adequate 74.4%, 88.3%, and 80.2% of the time, respectively. Overall 52.0% of cases received suboptimal management. Multivariate analysis revealed palliative intent was associated with improved documentation/clinical quality assurance (p = 0.07), decision making (p = 0.007), overall performance (p = 0.003), and optimal treatment rates (p = 0.07); non-small-cell lung cancer or central nervous system primary sites were associated with better decision making (p = 0.001), overall performance (p = 0.03), and optimal treatment rates (p = 0.002). CONCLUSIONS: Despite the poor results, the external audit had several benefits. It identified learning needs for future targeting, and the auditor provided facilitating feedback to address systematic errors identified. Our experience was also helpful in refining our national revalidation audit instrument. The feasibility of the external audit supports the consideration of including audit in national MOC programs.

Family centred decision making and non-disclosure of diagnosis in a South East Asian oncology practice.

AIM: To audit the extent of non-disclosure of cancer diagnosis (NDD) in South-East Asian patients referred to a Western trained oncologist, and determine the factors associated with this pattern of decision-making. METHODS: Over a 12-month period, all new patients referred to a single radiation oncologist's practice were prospectively audited at time of the initial consultation. Data obtained included patient demographic features, tumour details, proposed treatment and decision-making process. A shared decision-making consultation was attempted but if there was a persistent request by family to avoid disclosure, then a family-centred model was adopted. Patient autonomy was maintained by formally asking desire to participate in decision-making process, and subsequent permission then sought to involve family members as surrogates. Treatment aim, predicted median survival and NDD was recorded at end of consultation. Endpoints of patient NDD and non-discussion of prognosis were audited over a 12-month period, and factors potentially associated with these endpoints were assessed. RESULTS: Over a 12-month period 369 new patients were referred to the oncologist's practice. Forty per cent were >65 years, 84% Chinese race, and 66% non-English speaking. Lung (33%) and breast (32%) primaries were prominent. Forty-seven per cent were managed with palliative intent and 24% had expected median survivals of <6 months. NDD was recorded in 66 patients or 17% of the patient group. Quantitative discussion of prognosis was avoided in 36.8% of patients. On univariate analysis advanced patient age (p<0.001, OR=9.6, 95% CI 4.9-18.9), female sex (p=0.035, OR=1.8, 95% CI 1.04-3.1), non-English speaking (p<0.001, OR=21.4, 95% CI 5.1-89.1), palliative treatment aim (p<0.001, OR=5.9, 95% CI 3.1-11.2) and short expected median survival (p<0.001, OR=4.0, 95% CI 2.3-7.1) were associated with NDD. Advanced patient age (p<0.001, OR=7.9, 95% CI 3.6-17.5), female sex (p<0.001, OR=6.4, 95% CI 2.8-14.7), non-English speaking (p=0.010, OR=7.4, 95% CI 1.6-33.3) and palliative treatment aim (p=0.010, OR=3.3, 95% CI 1.3-8.0) remained significantly associated with NDD on multivariate logistic regression analysis. CONCLUSIONS: A high rate of desired NDD is evident in this Asian oncology population when a family-centred model to medical decision making is used. This data confirms that NDD and the model of decision making remains a significant ethical issue.

Comparison of magnetic resonance spectroscopy and perfusion-weighted imaging in presurgical grading of oligodendroglial tumors.

OBJECTIVE: Oligodendroglial tumors form an uncommon, but distinct, subgroup of gliomas with longer survival, better treatment response, and characteristic genetic alterations. Noninvasive grading of oligodendroglial tumors using functional and metabolic magnetic resonance imaging may be helpful in guiding the treatment approach and predicting malignant transformation of these tumors. We used perfusion-weighted magnetic resonance imaging and proton magnetic resonance spectroscopic imaging (MRSI) to predict the oligodendroglioma grade. METHODS: Twenty-four patients with pathologically confirmed oligodendrogliomas underwent dynamic contrast-enhanced perfusion-weighted magnetic resonance imaging and/or proton MRSI before surgery. We assessed the ability of tumor contrast enhancement, normalized cerebral blood volume, normalized choline, and the presence of either lactate or lipid metabolites to correctly predict the World Health Organization tumor grade. The accuracy of tumor grading using each method was also compared. RESULTS: Tumor contrast enhancement (P = 0.069) and normalized cerebral blood volume (P = 0.181) were not significantly different between low and high-grade oligodendrogliomas. The MRSI measurement of normalized choline was significantly higher in high-grade (2.82 +/- 0.64) than in low-grade (1.62 +/- 0.46) oligodendrogliomas (P < 0.001), and the presence of lactate or lipid metabolites also correctly predicted high-grade tumors (P = 0.014). The maximum accuracy of contrast enhancement, normalized cerebral blood volume, normalized choline, and lactate or lipid metabolites in grading oligodendroglioma was 71, 83, 90, and 85%, respectively. CONCLUSION: MRSI measurements are more accurate than perfusion-weighted magnetic resonance imaging or conventional contrast enhancement in differentiating oligodendroglial tumor grade. In these inherently vascular tumors, metabolic measurements of mitosis and necrosis may be better than measures of neovascularity in presurgical grading.

Evaluation of an audit with feedback continuing medical education program for radiation oncologists.

BACKGROUND: Meta-analyses demonstrate audit with feedback (AWF) is effective continuing medical education (CME). However, efficacy varies between specialties, with little published radiation oncologist (RO)-specific evidence. We evaluated an AWF CME intervention for ROs determining efficacy, cost-effectiveness, and participant satisfaction. METHODS: CME program: The CME incorporated fortnightly random patient chart audit, scoring management adequacy via a checklist. Scores were presented at a same-day institutional meeting, and case management discussed. Senior peers provided individualized, educational feedback. EVALUATION: Changes in behavior and performance were evaluated by chart review of new patients seen by ROs in the 2 months before commencement of AWF (T0), and at months 13-14 of the program (T1). Behavior and performance were evaluated with a validated, reproducible, 19-item instrument. Criteria for each case audited included 10 targeted and 3 nontargeted behavior items and 6 performance items; each scored 1 point if deemed adequate (maximum score 19). Cost-effectiveness was reported as cost to the institution per item point gained. The mean score (out of 5) of a 14-item questionnaire evaluated program perception. RESULTS: A total of 113 and 118 charts were evaluated at T0 and T1, respectively. Mean score of targeted behavior improved between T0 and T1 (from 8.7 to 9.2 out of 10, P = .0001), with no significant improvement of nontargeted behavior/performance items. Annual costs and cost-per-point gained were US 7,897 dollars and 15 dollars. Participant satisfaction was positive, increasing after efficacy result distribution (P = .0001). CONCLUSION: Audit with comparative, individualized, educational feedback is cost-effective and positively perceived CME, significantly improving targeted RO behavior. Oncologists' CME design and evaluation require further research.

A study of complications arising from different methods of anesthesia used in high-dose-rate brachytherapy for cervical cancer.

The purpose of this report is to review the complications related to different methods of anesthesia for high-dose-rate (HDR) brachytherapy for cervical carcinoma. All patients diagnosed with cervical cancer between 1999 and 2002 treated with 3-channel HDR brachytherapy were entered. Complications due to anesthesia for each fraction of brachytherapy were graded using the Common Toxicity Criteria. Eighty-four fractions of brachytherapy were delivered to 18 patients: 19 fractions with patients under general anesthesia (GA), 41 with patients under topical anesthesia and sedation, 5 with patients under paracervical nerve block, and 19 with patients under conscious sedation. Thirteen complications were reported: 12 related to GA and 1 due to paracervical nerve block. Of complications due to GA, 7 were grade 1 and 5 were grade 2. The complication due to paracervical nerve block (seizure) was grade 3. GA had significantly more complications than topical anesthesia or conscious sedation (both P < 0.001). HDR brachytherapy for cervical cancer under GA has significantly more complications than other methods. Given the increasing use of fractionated 3-channel brachytherapy, further investigation of risks and benefits of anesthetic techniques is required.

Evaluation of a radiotherapy protocol based on INT0116 for completely resected gastric adenocarcinoma.

PURPOSE: With the results of the INT0116 study, adjuvant radiochemotherapy has become the standard treatment after complete resection of gastric adenocarcinoma. However, the implementation of radiotherapy (RT) remains a concern. In response, consensus guidelines on RT technique have been published. Our objective was to measure the inter- and intraclinician variability in RT field delineation using conventional two- (2D) and three-dimensional (3D) techniques. METHODS AND MATERIALS: Between 1999 and 2003, five radiation oncologists (ROs) treated 45 patients with completely resected, gastric adenocarcinoma using postoperative radiochemotherapy (INT0116). Two cases were included in this study (Patient 1 had cardia and Patient 2 had antral disease). Standardized vignettes (with surgical and pathologic findings) and preoperative and postoperative imaging for each case were developed. Each RO designed AP-PA fields for each patient (2D planning) on two separate occasions. This was repeated using a 3D planning technique. RESULTS: Patient 1 had a mean field area of 250.2 cm(2) (SD 12.0) and 227.9 cm(2) (SD 26.5) using 2D and 3D planning, respectively (p = 0.03). The mean clinical target volume (CTV) volume was 468.3 cm(3) (SD 65.9). Patient 1 had a significantly greater inter- than intra-RO variation for the field area designed with 3D planning; however, no difference occurred with 2D planning or CTV contouring. Patient 2 had a mean field area of 234.8 cm(2) (SD 33.1) and 226.8 cm(2) (SD 19.3) using 2D and 3D planning, respectively (p = 0.5). The mean CTV was 729.4 cm(3) (SD 67.3). For Patient 2, the inter-RO variability was significantly greater than the intra-RO variability for the field area using both 2D and 3D planning, and no difference was seen for the CTV. Composite beam's-eye-view plots revealed that the superior, inferior, and right lateral borders proved to be most contentious. CONCLUSION: Despite published guidelines and a departmental protocol, significant variations in the RT field areas were seen among ROs for both 2D and 3D planning. However, in general, CTV contouring was reproducible. Because 3D-RT hinges on accurate target identification, caution should be exercised before migrating to 3D planning for postoperative gastric cancer.