A Pilot Clinical and Technical Validation of an Immersive Virtual Reality Platform for 3D Anatomical Modeling and Contouring in Support of Surgical and Radiation Oncology Treatment Planning.

The aim of this study was to validate a novel medical virtual reality (VR) platform used for medical image segmentation and contouring in radiation oncology and 3D anatomical modeling and simulation for planning medical interventions, including surgery. The first step of the validation was to verify quantitatively and qualitatively that the VR platform can produce substantially equivalent 3D anatomical models, image contours, and measurements to those generated with existing commercial platforms. To achieve this, a total of eight image sets and 18 structures were segmented using both VR and reference commercial platforms. The image sets were chosen to cover a broad range of scanner manufacturers, modalities, and voxel dimensions. The second step consisted of evaluating whether the VR platform could provide efficiency improvements for target delineation in radiation oncology planning. To assess this, the image sets for five pediatric patients with resected standard-risk medulloblastoma were used to contour target volumes in support of treatment planning of craniospinal irradiation, requiring complete inclusion of the entire cerebral-spinal volume. Structures generated in the VR and the commercial platforms were found to have a high degree of similarity, with dice similarity coefficient ranging from 0.963 to 0.985 for high-resolution images and 0.920 to 0.990 for lower resolution images. Volume, cross-sectional area, and length measurements were also found to be in agreement with reference values derived from a commercial system, with length measurements having a maximum difference of 0.22 mm, angle measurements having a maximum difference of 0.04°, and cross-sectional area measurements having a maximum difference of 0.16 mm2. The VR platform was also found to yield significant efficiency improvements, reducing the time required to delineate complex cranial and spinal target volumes by an average of 50% or 29 min.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2023 was held in Quebec City, Quebec 2-4 February 2023. The purpose of the conference was to develop consensus statements on emerging and evolving treatment paradigms. Participants included Canadian medical oncologists, radiation oncologists, pathologists and surgical oncologists from across Ontario, Quebec, and the Atlantic provinces. Consensus statements were developed following rapid review presentations and discussion of available literature. The recommendations proposed here represent the consensus opinions of physicians involved in the care of patients with gastrointestinal malignancies who participated in this meeting.

A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma.

BACKGROUND: Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%. AIMS: This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy. METHODS AND RESULTS: In this single-center, 20-year retrospective cohort study, we included patients who were <18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2 months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1-2 years after treatment completion, some children with these risk factors did not. CONCLUSION: Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

Diagnostic Accuracy of Centrally Restricted Diffusion Sign in Cerebral Metastatic Disease: Differentiating Radiation Necrosis from Tumor Recurrence.

Purpose: The centrally restricted diffusion sign of diffusion-weighted imaging (DWI) is associated with radiation necrosis (RN) in treated gliomas. Our goal was to evaluate its diagnostic accuracy to distinguish RN from tumor recurrence (TR) in treated brain metastases. Methods: Retrospective study of consecutive patients with brain metastases who developed a newly centrally necrotic lesion after radiotherapy (RT). One reader placed regions of interest (ROI) in the enhancing solid lesion and the non-enhancing central necrosis on the apparent diffusion coefficient (ADC) map. Two readers qualitatively assessed the presence of the centrally restricted diffusion sign. The final diagnosis was made by histopathology (n = 39) or imaging follow-up (n = 2). Differences between groups were assessed by Fisher's exact or Mann-Whitney U tests. Diagnostic accuracy and inter-reader agreement were evaluated using receiver operating characteristic (ROC) curve analysis and kappa scores. Results: Forty-one lesions (32 predominant RN; 9 predominant TR) were analyzed. An ADC value ≤ 1220 × 10-6 mm2/s (sensitivity 74%, specificity 89%, area under the curve [AUC] .85 [95% confidence interval {CI}, .70-.94] P < .0001) from the necrosis and an ADC necrosis/enhancement ratio ≤1.37 (sensitivity 74%, specificity 89%, AUC .82 [95% CI, .67-.93] P < .0001) provided the highest performance for RN diagnosis. The qualitative centrally restricted diffusion sign had a sensitivity of 69% (95% CI, .50-.83), specificity of 77% (95% CI, .40-.96), and a moderate (k = .49) inter-reader agreement for RN diagnosis. Conclusions: Radiation necrosis is associated with lower ADC values in the central necrosis than TR. A moderate interobserver agreement might limit the qualitative assessment of the centrally restricted diffusion sign.

Cranial Radiation Therapy as Salvage in the Treatment of Relapsed Primary CNS Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare malignancy. Standard of care is upfront high-dose methotrexate (HD-MTX) chemotherapy, while cranial radiation is more commonly used in the salvage setting. In this retrospective study, we aimed to investigate the safety and efficacy of salvage cranial radiation in PCNSL. PCNSL patients who received upfront HD-MTX chemotherapy and salvage cranial radiation after treatment failure between 1995 and 2018 were selected. Radiological response to cranial radiation was assessed as per Response Assessment in Neuro-Oncology Criteria. Twenty one patients were selected (median age 59.9 years), with median follow-up of 19.9 months. Fourteen patients (66.7%) received a boost to the gross tumour volume (GTV). Four patients (19.0%) sustained grade ≥2 treatment-related neurotoxicity post-completion of cranial radiation. Of the 19 patients who had requisite MRI with gadolinium imaging available for Response Assessment in Neuro-Oncology (RANO) criteria assessment, 47.4% achieved complete response, 47.4% achieved partial response, and 5.3% of patients exhibited stable disease. Higher dose to the whole brain (>30 Gy) was associated with higher rate of complete response (63.6%) than lower dose (≤30 Gy, 37.5%), while boost dose to the gross disease was also associated with higher rate of complete response (61.5%) compared with no boost dose (33.3%). Median overall survival was 20.0 months. PCNSL patients who relapsed following upfront chemotherapy showed a high rate of response to salvage cranial radiation, especially in those receiving greater than 30 Gy to the whole brain and boost to gross disease.

Risk of nephrogenic systemic fibrosis (NSF) in oncology patients receiving gadoxetic acid and updated risk of estimate of NSF in patients receiving gadoxetic acid with moderate and severe renal impairment.

OBJECTIVES: Gadoxetic acid (GA) is a half-biliary excreted gadolinium-based contrast agent (GBCA) administered at lower dose than gadobenic acid with similar ionic structure. Gadobenic acid is considered low-risk for nephrogenic systemic fibrosis (NSF) in patients with impaired renal function; however, safety of GA is unclear. The objective of this study was to determine the incidence of NSF in oncology patients undergoing GA-enhanced MRI and to update the risk estimate of NSF in patients receiving GA with severe renal impairment. MATERIALS AND METHODS: We retrospectively identified GA-enhanced MRI performed for treatment planning in confirmed cancer patients between March 2011 and December 2020. Serum creatinine values within 180 days of GA administration were retrieved and estimated glomerular filtration rate (eGFR) calculated. The eGFR value nearest to each MRI examination was used. The search result was linked to a prospectively maintained registry of reported cases of NSF. An updated literature review was conducted to identify published cases of NSF related to GA administration in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2 or on dialysis) and the incidence of NSF with 95% confidence intervals (CI) was determined combining published data with our results. RESULTS: 192 oncology patients underwent GA-enhanced MRI, mean age was 65.6 ± 11.8 years with 73 women. The mean eGFR was 89.6 ± 33.0 mL/min/1.73 m2. There were 33 patients with moderate (eGFR 30-60 mL/min/1.73 m2) and 1 patient with severe (eGFR < 30 mL/min/1.73 m2) renal impairment. There were no reported cases of NSF. Updated literature review including our results identified 340 patients with severe renal impairment or on dialysis with zero cases of NSF (0/340; 95% confidence intervals 0% and 0.9%). CONCLUSION: No cases of NSF were documented in this study related to gadoxetic acid use in oncology patients, including those with moderate and severe renal impairment. Recent data indicate use of gadoxetic acid in patients with renal impairment can be considered low-risk.

Resection and radiotherapy for intracranial ependymoma: a multiinstitutional 50-year experience.

OBJECTIVE: Maximal safe resection is the standard-of-care treatment for adults with intracranial ependymoma. The value of adjuvant radiotherapy remains unclear as these tumors are rare and current data are limited to a few retrospective cohort studies. In this study, the authors assembled a cohort of patients across multiple international institutions to assess the utility of adjuvant radiotherapy in this patient population. METHODS: Adults with intracranial ependymoma managed surgically at the University Health Network in Toronto, Canada, the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, and The Ottawa Hospital in Ottawa, Canada, were included in this study. The primary end points were progression-free survival (PFS) and overall survival (OS). Clinicopathological variables were assessed in univariate and multivariate Cox proportional hazard models for prognostic significance of PFS and OS. RESULTS: A total of 122 patients diagnosed between 1968 and 2019 were identified for inclusion. The majority of patients had grade II ependymomas on histopathology (78%) that were infratentorially located (71%), underwent gross-total (GTR) or near-total resection (NTR; 55%), and were treated with adjuvant radiotherapy (67%). A volumetric analysis of the extent of resection in 49 patients with available tumor volume data supported the accuracy of the categorical GTR, NTR, and subtotal resection (STR) groups utilized. Independent statistically significant predictors of poorer PFS in the multivariate analysis included STR or biopsy (vs GTR/NTR; HR 5.4, 95% confidence interval [CI] 2.4-11.0, p < 0.0001) and not receiving adjuvant radiotherapy; cranial (HR 0.5, 95% CI 0.2-1.1) and craniospinal (HR 0.2, 95% CI 0.04-0.5) adjuvant radiotherapy regimens improved PFS (p = 0.0147). Predictors of poorer OS in the multivariate analysis were grade III histopathology (vs grade II: HR 5.7, 95% CI 1.6-20.2, p = 0.0064) and undergoing a biopsy/STR (vs GTR/NTR: HR 9.8, 95% CI 3.2-30.1, p = 0.0001). CONCLUSIONS: The results of this 50-year experience in treating adult intracranial ependymomas confirm an important role for maximal safe resection (ideally GTR or NTR) and demonstrate that adjuvant radiotherapy improves PFS. This work will guide future studies as testing for molecular ependymoma alterations become incorporated into routine clinical practice.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

Stereotactic radiosurgery optimization with hippocampal-sparing in patients treated for brain metastases.

BACKGROUND AND PURPOSE: Cranial irradiation is associated with significant neurocognitive sequelae, secondary to radiation-induced damage to hippocampal cells. It has been shown that hippocampal-sparing (HS) leads to modest benefit in neurocognitive function in patients with brain metastases, but further improvement is possible. We hypothesized that improved benefits could be seen using HS in patients treated with stereotactic radiation (HS-SRS). Our study evaluated whether the hippocampal dose could be significantly reduced in the treatment of brain metastases using SRS, while maintaining target coverage. MATERIALS AND METHODS: Sixty SRS plans were re-planned to minimize dose to the hippocampus while maintaining target coverage. Patients with metastases within 5 mm of the hippocampus were excluded. Minimum, mean, maximum and dose to 40% (mean equivalent dose in 2 Gy per fraction, EQD2 to the hippocampus) were compared between SRS and HS-SRS plans. Median number of brain metastases was two. RESULTS: Compared to baseline SRS plans, hippocampal-sparing plans demonstrated Dmin was reduced by 35%, from 0.4 Gy to 0.3 Gy (p-value 0.02). Similarly, Dmax was reduced by 55%, from 8.2 Gy to 3.6 Gy, Dmean by 52%, from 1.6 Gy to 0.5 Gy, and D40 by 50%, from 1.8 Gy to 0.9 Gy (p-values <0.001). CONCLUSIONS: Our study demonstrated that further reduction of hippocampal doses of more than 50% is possible in the treatment of brain metastases with SRS using dose optimization. This could result in significantly improved neurocognitive outcomes for patients treated for brain metastases.

Dose-sparing effect of deep inspiration breath hold technique on coronary artery and left ventricle segments in treatment of breast cancer.

BACKGROUND AND PURPOSE: The risk of radiation-induced cardiac injury remains a challenging problem in the treatment of breast cancer. Certain cardiac structures receive higher doses than others, which results in variable frequencies of radiation-induced injuries across these structures. Radiation dose can be reduced using the deep inspiration breath hold (DIBH) technique. We aimed to investigate the dose reductions from DIBH in individual cardiac segments. MATERIALS AND METHODS: A dosimetric analysis was performed on left-sided breast cancer patients who underwent breast-conserving surgery and whole breast irradiation. Radiation doses to the cardiac structures were compared between the DIBH and free-breathing (FB) techniques and the dose reductions with DIBH were correlated to the lung expansion. RESULTS: For the 75 patients included in our study, DIBH effectively reduced doses to the heart, left lung, left anterior descending coronary artery (LAD) and left ventricle (LV), but the degree of dose reductions was variable across different structures. The absolute dose reductions were greatest in the distal LAD (14.4 Gy) and apical LV (12.1 Gy) segments, compared with the other LAD (middle 9.7 Gy, proximal 1.6 Gy) and LV (anterior 5.3 Gy, lateral 2.9 Gy, septal 2.0 Gy, inferior 0.2 Gy) segments. Left lung expansion was significantly correlated with the dose reductions in the LAD (Spearman's rank correlation coefficient, ρ, 0.304) and LV (ρ, 0.420) segments. CONCLUSIONS: Our study demonstrates the dose-sparing effects of DIBH in various cardiac structures, especially the distal LAD and apical LV segments. The large dose reductions seen in the distal LAD and apical LV segments could potentially translate into clinical benefit of reduced cardiac toxicity, as these structures have been previously shown to receive the highest doses and are associated with radiation-induced injury.

Whole brain radiotherapy improves survival outcomes in primary CNS lymphoma patients ineligible for systemic therapy.

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a very rare type of malignancy with a poor prognosis. The role of whole brain radiotherapy (WBRT) in PCNSL has been questioned due to the significant neurotoxicity and lack of convincing data for survival benefit. Even its role in a palliative setting remains to be clearly elucidated. Our study aims to investigate the benefit of WBRT in patients who are ineligible for systemic therapy. METHODS: A single-institution retrospective study was conducted on patients diagnosed with PCNSL between 2002 and 2017. Patients were excluded if they received systemic therapy or focal radiation only. Data on patient demographics and WBRT were collected and correlated with clinical outcomes. RESULTS: A total of 48 patients were selected for analysis, among which 31 (64.6%) patients received WBRT and 17 (35.4%) patients received supportive care only. Patient baseline characteristics were similar between the two groups. Median overall survival (OS) was 4.3 months among the entire cohort. WBRT was associated with improved median OS (8.0 months, range 1.4-62.3 months) compared with supportive care only (3.3 months, range 0.7-18.3 months) (HR 0.39, 95% CI 0.20-0.75, p = 0.005). Among patients who received WBRT, higher radiation dose to the whole brain was not associated with survival (p = 0.10), but higher radiation dose to the gross tumor was associated with improved survival (p = 0.007). CONCLUSION: Patients with PCNSL who are ineligible for systemic therapy may still benefit from WBRT with improvement in survival, compared with the best supportive care. Dose escalation through the addition of a gross tumor boost in these patients was associated with improved overall survival. Further studies in the prospective setting are necessary to confirm the findings from the study.

Hypofractionated radiotherapy for elderly breast cancer patients: from early stages disease to local palliation for unresectable disease.

There is a lack of clear guidelines on optimal radiotherapy dose regimen for elderly breast cancer patients. This review summarizes the current evidence on role of hypofractionated radiotherapy in elderly breast cancer. Also, suggestions have been provided on the best fractionation approaches based on current evidence. Hypofractionated radiotherapy is feasible and well tolerated in elderly breast cancer patients with both early and locally advanced disease. Ultra-hypofractionated regimen seem appropriate for palliation of unresectable primary breast disease and could become a safe approach for adjuvant treatments. Hypofractionated radiotherapy should be considered for treatment of elderly breast cancer for curative intent, as well as for palliation.

Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic ablative radiotherapy for medically inoperable stage I non-small cell lung cancer.

PURPOSE: In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). METHODS: Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50-60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0-1, 2-3, 4-9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. RESULTS: The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7-12 had an increased hazard of death on univariate analysis HR 2.45 (1.15-5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04-4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30-2.90) but not on multivariate analysis. On formalized testing - with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. CONCLUSION: We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

Feasibility, detectability and clinical experience with platinum fiducial seeds for MRI/CT fusion and real-time tumor tracking during CyberKnife® stereotactic ablative radiotherapy.

BACKGROUND AND PURPOSE: The purpose of this study is to review our experience with platinum fiducials in terms of feasibility of placement and detectability by both MRI and orthogonal x-ray images used in robotic SABR.Materials and Methods: 29 consecutive SABR patients (30 tumors) treated using fiducial tracking between January 2011 and February 2012 were reviewed. A total of 108 fiducials implanted in or around various tumor sites were identified. The pixel value contrast (PVC) of fiducials seen on MRI mages and treatment unit x-ray images of patients and phantoms were analysed. RESULTS: Migration rates were similar for PS versus GS and GC (6.2%). No difference was noted between the mean PVC in cirrhotic versus non-cirrhotic liver (60.4 vs. 47.9; p = 0.074). MRI sequences for tumors in the liver and other organs revealed a mean PVC for platinum superior to that of gold (p<0.001). No PVC difference was seen between gold and platinum on analysis of the treatment unit x-rays. CONCLUSION: Platinum seeds provide a superior detectability in comparison to gold seeds or coils on MRI images and are detected equally well by an image guidance system using orthogonal x-rays, making them a better choice for fiducial-based CT-MRI registration.

Stem cell niche irradiation in glioblastoma: providing a ray of hope?

Glioblastomas are organized hierarchically with a small number of glioblastoma stem cells that have unique self-renewal capacity and multilineage potency. The subventricular zone (SVZ) constitutes the largest neural stem cell niche in the adult human brain; it may also act as a reservoir of glioblastoma stem cells that can initiate, promote or repopulate a tumor. Incidental irradiation of SVZ has been shown to potentially influence outcomes suggesting that aggressively targeting the stem cell niche may offer a ray of hope in glioblastoma. The following review provides a summary of the experimental evidence supporting the origin and location of the putative glioblastoma stem cell in the SVZ, and offers a critical appraisal of the growing body of clinical evidence correlating SVZ dosimetry with outcomes in glioblastoma.

Treatment of metastatic liver tumors using stereotactic ablative radiotherapy.

The prognosis of patients with metastatic liver disease remains dismal with a median survival of only 6-12 mo. As 80%-90% of patients are not candidates for surgical therapy, there is a need for effective non-surgical therapies that would improve outcomes in these patients. The body of evidence related to the use of stereotactic ablative radiotherapy (SABR) in metastatic liver disease has substantially grown and evolved over the past decade. This review summarizes the current evidence supporting liver SABR with particular attention given to patient selection, target delineation, organ at risk dose volume constraints, response evaluation imaging and the various SABR techniques for delivering ablative radiotherapy to the liver. Even though it is unclear what dose-fractionation scheme, delivery system, concomitant therapy or patient selection strategy yields the optimum liver SABR outcomes, clear and growing evidence is available that SABR is a safe and effective therapy for the treatment of oligometastatic liver disease.

Pretreatment [18F]-fluoro-2-deoxy-glucose positron emission tomography maximum standardized uptake value as predictor of distant metastasis in early-stage non-small cell lung cancer treated with definitive radiation therapy: rethinking the role of positron emission tomography in personalizing treatment based on risk status.

PURPOSE: The aim of this study was to determine whether the preradiation maximum standardized uptake value (SUVmax) of the primary tumor for [(18)F]-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) has a prognostic significance in patients with Stage T1 or T2N0 non-small cell lung cancer (NSCLC) treated with curative radiation therapy, whether conventional or stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Between January 2007 and December 2011, a total of 163 patients (180 tumors) with medically inoperable histologically proven Stage T1 or T2N0 NSCLC and treated with radiation therapy (both conventional and SBRT) were entered in a research ethics board approved database. All patients received pretreatment FDG-PET / computed tomography (CT) at 1 institution with consistent acquisition technique. The medical records and radiologic images of these patients were analyzed. RESULTS: The overall survival at 2 years and 3 years for the whole group was 76% and 67%, respectively. The mean and median SUVmax were 8.1 and 7, respectively. Progression-free survival at 2 years with SUVmax <7 was better than that of the patients with tumor SUVmax ≥7 (67% vs 51%; P=.0096). Tumors with SUVmax ≥7 were associated with a worse regional recurrence-free survival and distant metastasis-free survival. In the multivariate analysis, SUVmax ≥7 was an independent prognostic factor for distant metastasis-free survival. CONCLUSION: In early-stage NSCLC managed with radiation alone, patients with SUVmax ≥7 on FDG-PET / CT scan have poorer outcomes and high risk of progression, possibly because of aggressive biology. There is a potential role for adjuvant therapies for these high-risk patients with intent to improve outcomes.

CyberKnife for inoperable renal tumors: Canadian pioneering experience.

INTRODUCTION: Stereotactic ablative body radiotherapy (SABR) is currently under study regarding its clinical application in management of patients with kidney tumors. CyberKnife can accurately deliver ablative tumor radiation doses while preserving kidney function. We report Canada's first use of CyberKnife SABR system in treating primary kidney tumors. MATERIALS AND METHODS: Between January 2011 and February 2012, we treated three patients with renal tumors using CyberKnife SABR. Two patients had tumors in solitary kidney. The third patient had a recurrent tumor after two previous radiofrequency ablation treatments. Platinum seed fiducials were used for real time tumor tracking. Magnetic resonance imaging registration was used for tumor delineation in all cases. The patients were followed with regular renal scans and renal function tests. RESULTS: The mean age was 79 years. Mean tumor size was 21.3 cm3. A dose of 39 Gy in 3 fractions was delivered. The post treatment follow up times were 15 months, 13 months and 12 months. Local control was obtained in all three patients. No acute or chronic toxicity was reported. Kidney functions remained unaffected after treatment. CONCLUSION: CyberKnife is technically feasible for treatment of medically inoperable renal tumors or tumors in a solitary kidney.

Can irradiation of potential cancer stem-cell niche in the subventricular zone influence survival in patients with newly diagnosed glioblastoma?

Glioblastoma progenitor or stem cells residing in the stem-cell niche in the subventricular zones (SVZ) can initiate or promote tumorigenesis. They can also migrate throughout the brain, resulting in disease progression. Irradiation of potential cancer stem-cell niche in the SVZ may influence survival. To analyze radiotherapy dose-volume parameters to the SVZ that correlate with survival in adequately treated patients with newly diagnosed glioblastoma, 40 adults with histopathologically proven supratentorial glioblastoma with available baseline imaging treated with postoperative conventionally fractionated focal conformal radiotherapy plus chemotherapy, available radiotherapy planning dataset, and documented event of progression or death or minimum 6-month follow-up were included in this retrospective study. Dose-volume parameters to the SVZ were extracted from treatment planning system and analyzed in relation to survival outcomes. Mean ipsilateral and contralateral SVZ volumes were 5.6 and 6.4 cc, respectively. With median follow-up of 15 months (interquartile range 12-18 months), median [95 % confidence interval (CI)] progression-free survival (PFS) and overall survival (OAS) was 11 months (95 % CI 8.9-13.0 months) and 17 months (95 % CI 11.6-22.4 months), respectively. Older age (>50 years), poor recursive partitioning analysis (RPA) class, and higher than median of mean contralateral SVZ dose were associated with significantly worse PFS and OAS. Multivariate analysis identified RPA class, Karnofsky performance status, and mean ipsilateral SVZ dose as independent predictors of survival. Increasing mean dose to the ipsilateral SVZ was associated with significantly improved OAS. Irradiation of potential cancer stem-cell niche influences survival outcomes in patients with newly diagnosed glioblastoma.

Concordance between local, institutional, and central pathology review in glioblastoma: implications for research and practice: a pilot study.

BACKGROUND: There is significant inter-observer variation amongst the neuro-pathologists in the typing, subtyping, and grading of glial neoplasms for diagnosis. Centralized pathology review has been proposed to minimize this inter-observer variation and is now almost mandatory for accrual into multicentric trials. We sought to assess the concordance between neuro-pathologists on histopathological diagnosis of glioblastoma. MATERIALS AND METHODS: Comparison of local, institutional, and central neuro-oncopathology reporting in a cohort of 34 patients with newly diagnosed supratentorial glioblastoma accrued consecutively at a tertiary-care institution on a prospective trial testing the addition of a new agent to standard chemo-radiation regimen. RESULTS: Concordance was sub-optimal between local histological diagnosis and central review, fair between local diagnosis and institutional review, and good between institutional and central review, with respect to histological typing/subtyping. Twelve (39%) of 31 patients with local histological diagnosis had identical tumor type, subtype and grade on central review. Overall agreement was modestly better (52%) between local diagnosis and institutional review. In contrast, 28 (83%) of 34 patients had completely concordant histopathologic diagnosis between institutional and central review. The inter-observer reliability test showed poor agreement between local and central review (kappa statistic=0.12, 95% confidence interval (CI): -0.03-0.32, P=0.043), but moderate agreement between institutional and central review (kappa statistic=0.51, 95%CI: 0.17-0.84, P=0.00003). Agreement between local diagnosis and institutional review was fair. CONCLUSIONS: There exists significant inter-observer variation regarding histopathological diagnosis of glioblastoma with significant implications for clinical research and practice. There is a need for more objective, quantitative, robust, and reproducible criteria for better subtyping for accurate diagnosis.