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Hurdles in radiation planning for glioblastoma: Can delayed‐contrast enhanced computed tomography be a potential solution?
... Planning CT scans were taken with patients in supine position and immobilized with a three clamp orfit cast. Imaging acquisition protocol required a slice thickness of 2.5 mm in a multislice CT scanner (GE Healthcare Technologies, WI, USA), both immediately (within 15 s) and delayed, in other words, 10 min after injection of contrast [6]. The images were then transferred to the Eclipse™ treatment planning system (v.8.6, Varian Medical Systems, CA, USA). ...
Aim
The purpose of the study is to perform a dosimetric analysis of the doses received by planning target volume and organ at risks in the postoperative glioblastoma by using 3D-conformal radiotherapy to a total dose of 60 Gy in 30 fractions.
Materials & Methods
All patients received concurrent temozolomide every day, and this was followed by adjuvant temozolomide of 5 days of treatment per month.
Results
More than 98% of patients were treated with a dose of 60 Gy. Doses were analyzed for the normal whole brain, tumor volume, as well as all the organs at risk.
Conclusion
Given the grave prognosis and the limited survival of glioblastoma despite the best treatment available, makes 3D-conformal radiotherapy an equally acceptable treatment option.
Background
Adjuvant therapy is an important tool in the arsenal of brain tumor management and can improve patients' outcomes significantly but low- and middle-income countries (LMICs) often face challenges in provision. Therefore, our study aims to highlight barriers and strategies to adjuvant therapy of brain tumors in low-resource settings.
Method
A comprehensive search of literature was conducted using PubMed, CINAHL, Google Scholar, and Scopus, from inception to October 20, 2022. The review included studies on adjuvant therapy for brain tumors in LMICs and identified themes using the National Surgical, Obstetric, and Anesthesia Plan (NSOAP) domains.
Results
32 studies were included in the review. The most reported barriers to adjuvant care were limited access to healthcare (14 %), limited access to chemotherapy and radiation equipment (25 %), and traditional or alternative medications (11 %). Strategies for improvement include improving the availability of specialized radiation oncology training (8 %) and improving access to neuro-diagnostics and neurotherapeutics (12 %). In addition, efforts to subsidize treatment (4 %) and provide financial coverage through the Ministry of Health (4 %) can help to address the high cost of care and improve access to funding for chemotherapy. Finally, establishing documentation systems and registries (16 %), implementing standardized national treatment guidelines (8 %) can help to improve overall care for brain tumor patients in LMICs.
Conclusion
A multimodal approach of strategies targeting workforce, infrastructure, service delivery, financing, and information management is needed to improve adjuvant care for brain tumors. International collaboration and partnerships can also play a key role in addressing barriers and improving care in LMICs.
For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.
Purpose:
To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem.
Methods and materials:
The American Society for Radiation Oncology (ASTRO) convened the Glioblastoma Guideline Panel to perform a systematic literature review investigating the following: (1) Is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects? (2) What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status? (3) What are ideal target volumes for curative-intent external beam radiation therapy of glioblastoma? (4) What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy? Guideline recommendations were created using predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength.
Results:
Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with concurrent and adjuvant temozolomide. Routine addition of bevacizumab to this regimen is not recommended. Elderly patients (≥70 years of age) with reasonable performance status should receive hypofractionated radiation therapy (eg, 40 Gy in 2.66-Gy fractions); preliminary evidence may support adding concurrent and adjuvant temozolomide to this regimen. Partial brain irradiation is the standard paradigm for radiation delivery. A variety of acceptable strategies exist for target volume definition, generally involving 2 phases (primary and boost volumes) or 1 phase (single volume). For recurrent glioblastoma, focal reirradiation can be considered in younger patients with good performance status.
Conclusions:
Radiation therapy occupies an integral role in treating glioblastoma. Whether and how radiation therapy should be applied depends on characteristics specific to tumor and patient, including age and performance status.
Contrast material enhancement for cross-sectional imaging has been used since the mid 1970s for computed tomography and the mid 1980s for magnetic resonance imaging. Knowledge of the patterns and mechanisms of contrast enhancement facilitate radiologic differential diagnosis. Brain and spinal cord enhancement is related to both intravascular and extravascular contrast material. Extraaxial enhancing lesions include primary neoplasms (meningioma), granulomatous disease (sarcoid), and metastases (which often manifest as mass lesions). Linear pachymeningeal (dura-arachnoid) enhancement occurs after surgery and with spontaneous intracranial hypotension. Leptomeningeal (pia-arachnoid) enhancement is present in meningitis and meningoencephalitis. Superficial gyral enhancement is seen after reperfusion in cerebral ischemia, during the healing phase of cerebral infarction, and with encephalitis. Nodular subcortical lesions are typical for hematogenous dissemination and may be neoplastic (metastases) or infectious (septic emboli). Deeper lesions may form rings or affect the ventricular margins. Ring enhancement that is smooth and thin is typical of an organizing abscess, whereas thick irregular rings suggest a necrotic neoplasm. Some low-grade neoplasms are "fluid-secreting," and they may form heterogeneously enhancing lesions with an incomplete ring sign as well as the classic "cyst-with-nodule" morphology. Demyelinating lesions, including both classic multiple sclerosis and tumefactive demyelination, may also create an open ring or incomplete ring sign. Thick and irregular periventricular enhancement is typical for primary central nervous system lymphoma. Thin enhancement of the ventricular margin occurs with infectious ependymitis. Understanding the classic patterns of lesion enhancement--and the radiologic-pathologic mechanisms that produce them--can improve image assessment and differential diagnosis.
The management of glioblastoma multiforme (GBM) in developing countries is hindered by the paucity of clear protocols due in part to growing economic constraints and the lack of availability of expensive chemotherapeutic agents. We evaluated the deliverable treatment protocols and achievable outcomes for patients with GBM in a low-income country prior and subsequent to the worldwide adoption of temozolomide.
Retrospective case series.
Charts of consecutive patients with a pathologic diagnosis of high-grade glioma diagnosed between January 2003 and December 2008 were retrospectively reviewed.
We identified 146 adult patients, including 105 males and 41 females between 19 and 81 years of age (median age, 51 years), with histologically confirmed high-grade glioma. All patients underwent craniotomy. Eighty-two patients were treated with radiotherapy and temozolomide, of whom 42 patients received temozolomide concurrent with radiation followed by adjuvant temozolomide; 40 patients received irradiation followed sequentially by 6 cycles of temozolomide. In 40 patients irradiation was utilized as a single modality treatment adjuvant to surgery. The follow-up ranged from 1 to 56 months (median, 9.4 months). The median survival for the whole cohort was 10.2 months. The median survival for the radiotherapy-alone group was 5.3 months and for combined radiotherapy/temozolomide was 14.8 months. Survival was similar in both concurrent and sequential groups. Temozolomide conferred a statistically significant survival benefit of 9 months compared with standard therapeutic modalities.
The results compare favorably to those reported in developed nations. Current management of GBM in developing countries should include maximal surgical resection followed by radiotherapy/temozolomide whenever medically and/or financially feasible. Outcomes comparable to those obtained within the context of randomized trials can be expected in low-income settings if healthcare delivery is carefully planned. Our results indicate that concurrent and sequential regimens are equally effective in these patients.
To determine the effect of waiting time for radiotherapy on the overall survival of patients with high-grade gliomas.
We examined records of patients with grade III/IV gliomas who were referred to radiotherapy after surgery or biopsy - ECOG <3, any age, radical intent or palliative intent with dose >50 Gy, no interstitial or radiosurgery boost. Waiting time was defined in two ways, time from biopsy to radiotherapy and time from presentation to radiotherapy department to start of radiotherapy.
There were 182 patients in the study having a median survival of 8.5 months, with a median follow up of 10.5 months. The group comprised of 63 (35%) grade III and 119 (65%) grade IV gliomas. Median times and ranges from biopsy and presentation to treatment were 26 days (4-78 days) and 15 days (1-62 days), respectively. The median dose was 60 Gy in a median of 30 fractions over a median of 46 days. Tumour progression before and during radiotherapy occurred in seven patients (4%) and 19 patients (11%), respectively. One hundred and seventy-nine patients died of disease. The seven patients whose tumour progressed before radiotherapy were excluded from the analysis of prognostic variables. In a multivariate analysis the variables that were significantly associated with worse survival were older age, reduced dose and prolonged waiting time from presentation. The risk of death increased by 2% for each day of waiting for radiotherapy.
The study showed longer waiting time from presentation at radiotherapy department to treatment to be a significant predictor of overall survival for patients with high-grade glioma.
Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that is distinguished pathologically from lower grade tumors by necrosis and microvascular hyperplasia. Necrotic foci are typically surrounded by "pseudopalisading" cells-a configuration that is relatively unique to malignant gliomas and has long been recognized as an ominous prognostic feature. Precise mechanisms that relate morphology to biologic behavior have not been described. Recent investigations have demonstrated that pseudopalisades are severely hypoxic, overexpress hypoxia-inducible factor (HIF-1), and secrete proangiogenic factors such as VEGF and IL-8. Thus, the microvascular hyperplasia in GBM that provides a new vasculature and promotes peripheral tumor expansion is tightly linked with the emergence of pseudopalisades. Both pathologic observations and experimental evidence have indicated that the development of hypoxia and necrosis within astrocytomas could arise secondary to vaso-occlusion and intravascular thrombosis. This emerging model suggests that pseudopalisades represent a wave of tumor cells actively migrating away from central hypoxia that arises after a vascular insult. Experimental glioma models have shown that endothelial apoptosis, perhaps resulting from angiopoetin-2, initiates vascular pathology, whereas observations in human tumors have clearly demonstrated that intravascular thrombosis develops with high frequency in the transition to GBM. Tissue factor, the main cellular initiator of thrombosis, is dramatically upregulated in response to PTEN loss and hypoxia in human GBM and could promote a prothrombotic environment that precipitates these events. A prothrombotic environment also activates the family of protease activated receptors (PARs) on tumor cells, which are G-protein-coupled and enhance invasive and proangiogenic properties. Vaso-occlusive and prothrombotic mechanisms in GBM could readily explain the presence of pseudopalisading necrosis in tissue sections, the rapid peripheral expansion on neuroimaging, and the dramatic shift to an accelerated rate of clinical progression resulting from hypoxia-induced angiogenesis.
Fractionated external beam radiotherapy is an important component of standard treatment for high grade glioma. Due to resource constraints, patients may experience delays in receiving treatment. The purpose of this study was to evaluate the effect of radiotherapy waiting time on survival in patients with high grade glioma. A retrospective analysis was performed of 172 patients with a histological diagnosis of WHO Grade 3 or 4 Astrocytoma who had undergone surgery at Wellington Hospital between 1993 and 2003, and who subsequently underwent radiotherapy. Time to radiotherapy after surgery varied from 7 days to over 16 weeks. Multiple Cox regression analysis showed that age, performance status, tumour grade, extent of surgical resection, radiotherapy dose, and time to radiotherapy from day of surgery were all independently related to survival. Every additional week of delay until the start of radiotherapy increases the risk of death (hazard ratio) by 8.9% (95%CI 2.0%-16.1%). A 6 week delay in starting radiotherapy (from 2 weeks post-op to 8 weeks) reduces median survival by 11 weeks for a typical patient. Delay in radiotherapy results in a clinically significant reduction in survival. These findings have implications for resource allocation and for the design of clinical trials.
Glioblastoma (GBM) is a highly malignant, rapidly progressive astrocytoma that is distinguished pathologically from lower grade tumors by necrosis and microvascular hyperplasia. Necrotic foci are typically surrounded by "pseudopalisading" cells-a configuration that is relatively unique to malignant gliomas and has long been recognized as an ominous prognostic feature. Precise mechanisms that relate morphology to biologic behavior have not been described. Recent investigations have demonstrated that pseudopalisades are severely hypoxic, overexpress hypoxia-inducible factor (HIF-1), and secrete proangiogenic factors such as VEGF and IL-8. Thus, the microvascular hyperplasia in GBM that provides a new vasculature and promotes peripheral tumor expansion is tightly linked with the emergence of pseudopalisades. Both pathologic observations and experimental evidence have indicated that the development of hypoxia and necrosis within astrocytomas could arise secondary to vaso-occlusion and intravascular thrombosis. This emerging model suggests that pseudopalisades represent a wave of tumor cells actively migrating away from central hypoxia that arises after a vascular insult. Experimental glioma models have shown that endothelial apoptosis, perhaps resulting from angiopoetin-2, initiates vascular pathology, whereas observations in human tumors have clearly demonstrated that intravascular thrombosis develops with high frequency in the transition to GBM. Tissue factor, the main cellular initiator of thrombosis, is dramatically upregulated in response to PTEN loss and hypoxia in human GBM and could promote a prothrombotic environment that precipitates these events. A prothrombotic environment also activates the family of protease activated receptors (PARs) on tumor cells, which are G-protein-coupled and enhance invasive and proangiogenic properties. Vaso-occlusive and prothrombotic mechanisms in GBM could readily explain the presence of pseudopalisading necrosis in tissue sections, the rapid peripheral expansion on neuroimaging, and the dramatic shift to an accelerated rate of clinical progression resulting from hypoxia-induced angiogenesis.
Deep brain stimulation is typically performed with intraoperative microelectrode recording and test stimulation for target confirmation. Recent studies have shown accurate, clinically efficacious results after lead placement without microelectrode recording or test stimulation, using interventional magnetic resonance imaging (MRI) or intraoperative computed tomography (CT; iCT) for verification of accuracy. The latter relies on CT–MRI fusion. To validate CT–MRI fusion in this setting, we compared stereotactic coordinates determined intraoperatively using CT–MRI fusion with those obtained on postoperative MRI. Deep brain stimulation electrodes were implanted with patients under general anesthesia. Direct targeting was performed on preoperative MRI, which was merged with preimplantation iCT images for stereotactic registration and postimplantation iCT images for accuracy confirmation. Magnetic resonance imaging was obtained 6 weeks postoperatively for comparison. Postoperative MRI was obtained for 48 patients, with 94 leads placed over a 1-year period. Vector error of the targeted contact relative to the initial plan was 1.1 ± 0.7 mm on iCT and 1.6 ± 0.7 mm on postoperative MRI. Variance comparisons (F-tests) showed that the discrepancy between iCT- and postoperative MRI-determined errors was attributable to measurement error on postoperative MRI, as detected in inter-rater reliability testing. In multivariate analysis, improved lead placement accuracy was associated with frame-based stereotaxy with the head of the bed at 0° compared with frameless stereotaxy with the head of the bed at 30° (P = 0.037). Intraoperative CT can be used to determine lead placement accuracy in deep brain stimulation surgery. The discrepancy between coordinates determined intraoperatively by CT–MRI fusion and postoperatively by MRI can be accounted for by inherent measurement error. © 2014 International Parkinson and Movement Disorder Society
Background:
Glioblastoma multiforme is the most common malignant primary brain tumor in adults and is associated with poor survival rates. Symptoms often include headaches; nausea and vomiting; and progressive memory, personality, or neurologic deficits. The treatment remains a challenge, and despite the approval of multiple new therapies in the past decade, survival has not improved.
Objective:
To describe treatment patterns, survival, and healthcare costs of patients with incident glioblastoma in a large US population.
Methods:
For this population-based study, adult patients (aged ≥18 years) with incident malignant brain neoplasm who had undergone brain surgery between January 1, 2006, and December 31, 2010, were identified in the Truven Health Analytics MarketScan Research Databases. The patients were stratified into 4 cohorts based on the use of temozolomide and/or external beam radiation therapy within 90 days after brain surgery (ie, the index event). Treatment patterns, survival, and healthcare costs were assessed until patient death, disenrollment, or the end-of-study period.
Results:
A total of 2272 patients met the inclusion criteria; of these, 37% received temozolomide and radiation therapy, 13.8% received radiation alone, 3.9% received temozolomide alone, and 45.3% of patients received neither. The average patient age ranged from 55.3 years to 59.8 years across the study cohorts; between 29.8% and 44% of patients in each cohort were female. The duration of temozolomide use was similar between the temozolomide-only cohort and patients receiving temozolomide with external beam radiation; approximately 76% of patients received temozolomide at least 60 days, dropping to 48.1% and 23% at 180 days and 360 days of follow-up, respectively. The median survival was 456 days, ranging from 331 days in the temozolomide-only cohort to 529 days in the cohort that received neither temozolomide nor external beam radiation. The average total costs in the 6 months postindex were 79,099 for patients who received neither temozolomide nor radiation to $138,767 for those who received both therapies.
Conclusion:
The survival patterns of patients with glioblastoma seen in this real-world study of current treatments in a clinical setting is similar to the survival rate reported in clinical trials. However, further cost-effectiveness and quality-of-life analyses will be critical to better understand the role of temozolomide therapy in this patient population, considering its considerable cost burden and potential negative impact on survival seen in this study.
A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.
Fifty patients undergoing cranial CT had expanded-high-iodine-dose (EHID) scans. The EHID was given either as an additional bolus dose (37--40 g iodine) after a routine infusion contrast scan (42.3 g), or as a continuous infusion (total 74--80 g). Diseases presented include primary and metastatic neoplasm, pituitary neoplasm, and demyelinating disease. The results suggest that the primary usefulness of the EHID is in (a) detecting multiple rather than solitary brain lesions, (b) the definitive demonstration of an equivocal area of abnormal enhancement, and (c) differentiating solid histologically microcystic from frankly macrocystic neoplasms.
Quantitative 3-D volumetric comparisons were made of composite CT-MRI macroscopic and microscopic tumor and target volumes to their independently defined constituents. Volumetric comparisons were also made between volumes derived from coronal and axial MRI data sets, and between CT and MRI volumes redefined at a repeat session in comparison to their original definitions. The degree of 3-D dose coverage obtained from use of CT data only or MRI data only in terms of coverage of composite CT-MRI volumes was also analyzed. On average, MRI defined larger volumes as well as a greater share of composite CT-MRI volumes. On average, increases in block margin on the order of 0.5 cm would have ensured coverage of volumes derived from use of both imaging modalities had only MRI data been used. However, the degree of inter-observer variation in volume definition is on the order of the magnitude of differences in volume definition seen between the modalities, and the question of which imaging modality best describes tumor volumes remains unanswered until detailed histologic studies are performed. Given that tumor volumes independently apparent on CT and MRI have equal validity, composite CT-MRI input should be considered for planning to ensure precise dose coverage for conformal treatments.
Within 3 weeks of definitive surgery, 571 adult patients with histologically confirmed, supratentorial malignant gliomas were randomly assigned to receive one of three chemotherapy regimens: BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea) alone, alternating courses (every 8 weeks) of BCNU and procarbazine, or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 (epipodophyllotoxin). Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy. Patients accrued in 1982 and 1983 were randomly assigned to receive either whole-brain irradiation as above, or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume. The data were analyzed for the total randomized population and separately for the 510 patients, termed the "Valid Study Group (VSG)," who met protocol eligibility specifications (including central pathology review), 80% of whom had glioblastoma multiforme. The median survival times from time of randomization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months, and 29% to 37% of the patients survived for 18 months (life-table estimate); the differences between these groups were not statistically significant. Survival differences between the radiotherapy groups were small and not statistically significant. It is concluded that, for malignant glioma, giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation, and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone.
This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)
Pathological findings in 20 cases of glioblastoma multiforme were correlated with clinical histories and computerized tomographic (CT) scans. This was done to define the neoplasm in three stages: before treatment, during remission, and during recurrence.
The untreated lesions were markedly cellular neoplasms composed predominantly of small anaplastic cells. The radiographic central region of low density was necrosis, the enhancing rim was a cellular zone of viable neoplasm, and the perilesional low-density area was edema with infiltrating tumor. In these 20 cases, all of the identifiable neoplasms lay within the zone of peritumoral edema or contrast enhancement, although small anaplastic cells may have been present in more distant regions. The lesions in remission were remarkable for their minimal mass effect, discrete nature, extensive necrosis, and content of large bizarre glia. The large cells were confined to the original tumor bed and were consistent with neoplastic cells inactivated and immobilized by radio- and chemotherapy. These lesions were accurately localized by CT scanning. The recurrent lesions were heterogeneous, but most were formed of widely disseminated small anaplastic cells. The highly cellular regions of such lesions could be localized by CT scanning, but CT could not detect less cellular foci in the cerebrum, cerebellum, or brain stem. In one patient, the contrast-enhancing lesions of “recurrence,” were foci of radionecrosis, underscoring the difficulty in distinguishing this entity from recurrent neoplasm.
A prospective clinical study was done on 20 patients referred for computed tomography within 28 hr of a cerebral ischemic event. The patients were scanned before, immediately after, and 3 hr after a high dose of intravenous contrast medium was administered to produce prolonged high blood iodine levels. In seven patients the delayed scan demonstrated a heretofore undescribed type of contrast enhancement which represents the early massive vasogenic edema seen in experimental animals before confluent hemorrhagic infarction. Four of the seven patients developed hemorrhagic infarction. None of the remaining 11 patients with cerebral infarctions and conventional postenhancement CT patterns showed hemorrhage on follow-up CT scans or at autopsy. Two patients with transient ischemic attacks had normal CT scans. It may now be possible to predict patients in whom there is high probability of hemorrhagic infarction before blood appears on CT. Treatment of these patients should probably be aimed at preventing the devastating effects of the vasogenic edema. We speculate that heparinization or bypass surgery to reestablish circulation may be contraindicated in this group.
One hundred cranial computed tomograms of adults with known or suspected intracranial neoplasm were analyzed retrospectively. Rapid high-dose intravenous contrast infusion (84.6 g l) was followed by immediate and 1 1/2-hour delayed scans. Delayed images afforded more information than the initial series in 67% of cases. 11.5% false-negative examinations (i.e., no tumor reported) would have resulted if studies were terminated after the immediate post-infusion scans. No patient experienced clinically detectable renal compromise.
We describe an image fusion application that addresses two basic problems that previously limited the use of magnetic resonance imaging (MRI) for geometric localization in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). The first limitation is imposed by the use of a relocatable, MRI-incompatible, stereotactic frame for stereotactic radiotherapy. The second limitation is an inherent lack of geometric fidelity in current MRI scanners that invalidates the use of MRI for stereotactic localization.
We recently developed and implemented a novel automated method for fusing computerized tomography (CT) and MRI volumetric image studies. The method is based on a chamfer matching algorithm, and provides a quality assurance procedure to verify the accuracy of the fused image set. The image fusion protocol removes the need for stereotactic fixation of the patient for the MRI study.
The image fusion protocol significantly improves on the spatial accuracy of the MRI study. We demonstrate the effect of distortion and the effectiveness of the fusion with a phantom study. We present two case studies, an acoustic neurinoma treated with SRS, and a pilocytic astrocytoma treated with SRT.
The image fusion protocol significantly improves our logistical management of treating patients with radiosurgery and makes conformal therapy practical for treating patients with SRT. The image fusion protocol demonstrates both the superior diagnostic quality and the poor geometric fidelity of MRI. MRI is a required imaging modality in stereotactic therapy. Image fusion combines the superior MRI diagnostic quality with the superior CT geometric definition, and makes the use of MRI in stereotactic therapy possible and practical.
This paper deals with the impact MRI may have on radiotherapy treatment planning of brain tumors. The authors analyzed differences in size and position of treatment fields as indicated by three observers (two radiotherapists and one neuroradiologist) using CT or MR based radiotherapy planning procedures for cerebral-gliomas. Large differences in field size and position were found in non CT contrast enhancing tumors, all low grade gliomas. Small differences were found in contrast enhancing lesions including the high grade gliomas. We conclude that implementation of MRI in radiotherapy treatment planning leads to a greater precision in treatment fields for non CT contrast enhancing lesions.
The emerging utilisation of conformal radiotherapy (RT) planning requires sophisticated imaging modalities. Magnetic resonance imaging (MRI) has introduced several added imaging benefits that may confer an advantage over the use of computed tomography (CT) in RT planning such as improved soft tissue definition, unrestricted multiplannar and volumetric imaging as well as physiological and biochemical information with magnetic resonance (MR) angiography and spectroscopy. However, MRI has not yet seriously challenged CT for RT planning in most sites. The reasons for this include: (1) the poor imaging of bone and the lack of electron density information from MRI required for dosimetry calculations; (2) the presence of intrinsic system-related and object-induced MR image distortions; (3) the paucity of widely available computer software to accurately and reliably integrate and manipulate MR images within existing RT planning systems. In this review, the basic principals of MRI with its present potential and limitations for RT planning as well as possible solutions will be examined. Methods of MRI data acquisition and processing including image segmentation and registration to allow its application in RT planning will be discussed. Despite the difficulties listed, MRI has complemented CT-based RT planning and in some regions of the body especially the brain, it has been used alone with some success. Recent work with doped gel compounds allow the MRI mapping of dose distributions thus potentially providing a quality assurance tool and in a manner analogous to CT, the production of dose-response information in the form of dose volume histograms. However, despite the promise of MRI, much development research remains before its full potential and cost-effectiveness can be assessed.
To examine a statistical validation method based on the spatial overlap between two sets of segmentations of the same anatomy.
The Dice similarity coefficient (DSC) was used as a statistical validation metric to evaluate the performance of both the reproducibility of manual segmentations and the spatial overlap accuracy of automated probabilistic fractional segmentation of MR images, illustrated on two clinical examples. Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated manual segmentations of the prostate peripheral zone were performed separately on preoperative and on intraoperative images. Example 2: A semi-automated probabilistic fractional segmentation algorithm was applied to MR imaging of 9 cases with 3 types of brain tumors. DSC values were computed and logit-transformed values were compared in the mean with the analysis of variance (ANOVA).
Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with 1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI (P < .001) were within and at the margin of the range of good reproducibility, respectively. Example 2: Wide ranges of DSC were observed in brain tumor segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other mixed gliomas (0.490-0.899).
The DSC value is a simple and useful summary measure of spatial overlap, which can be applied to studies of reproducibility and accuracy in image segmentation. We observed generally satisfactory but variable validation results in two clinical applications. This metric may be adapted for similar validation tasks.
In radiotherapy planning of head and neck tumors, coregistration of various anatomical (e.g. CT and MRI) and functional (e.g. PET) images is a promising way to improve the delineation of the target volumes. In this paper, we report data on accuracy, reproducibility and consistency of an interactive coregistration procedure in a specifically designed phantom and in a group of patients with primary head and neck tumors.
A phantom and a group of four patients with pharyngo-laryngeal tumors were imaged by CT scan (taken as the reference image), MRI (T1- and T2-weighed sequences) and PET (transmission and FDG emission). Sets of images were coregistered using an interactive rigid coregistration method based on interactive surface segmentation. Translational and rotational displacements relative to the reference CT scan were measured and expressed in terms of accuracy, reproducibility (inter- and intra-observer variation) and consistency (between T1- and T2-weighed MRI).
Coregistration accuracy was in the range of 0.8-6.2 mm and 1.2-4.6 mm for the phantom and the patients, respectively. Accuracy was slightly worse in the z direction, and was significantly correlated with the spatial resolution of the imaging modalities, at least for the phantom. Inter- and intra-observer variations were very small and always far below the residual variance. Consistency was perfect except in the y direction.
Providing adequate set-up is chosen, accurate coregistration of CT, MR and FDG-PET images can be obtained in the head and neck area. Coregistration was consistent and highly reproducible among observers.
To evaluate the spatial relationship between peritumoral edema and recurrence pattern in patients with glioblastoma (GBM).
Forty-eight primary GBM patients received three-dimensional conformal radiotherapy that did not intentionally include peritumoral edema within the clinical target volume between July 2000 and June 2001. All 48 patients have subsequently recurred, and their original treatment planning parameters were used for this study. New theoretical radiation treatment plans were created for the same 48 patients, based on Radiation Therapy Oncology Group (RTOG) target delineation guidelines that specify inclusion of peritumoral edema. Target volume and recurrent tumor coverage, as well as percent volume of normal brain irradiated, were assessed for both methods of target delineation using dose-volume histograms.
A comparison between the location of recurrent tumor and peritumoral edema volumes from all 48 cases failed to show correlation by linear regression modeling (r(2) = 0.0007; p = 0.3). For patients with edema >75 cm(3), the percent volume of brain irradiated to 46 Gy was significantly greater in treatment plans that intentionally included peritumoral edema compared with those that did not (38% vs. 31%; p = 0.003). The pattern of failure was identical between the two sets of plans (40 central, 3 in-field, 3 marginal, and 2 distant recurrence).
Clinical target volume delineation based on a 2-cm margin rather than on peritumoral edema did not seem to alter the central pattern of failure for patients with GBM. For patients with peritumoral edema >75 cm(3), using a constant 2-cm margin resulted in a smaller median percent volume of brain being irradiated to 30 Gy, 46 Gy, and 50 Gy compared with corresponding theoretical RTOG plans that deliberately included peritumoral edema.
The analysis of MR images is evolving from qualitative to quantitative. More and more, the question asked by clinicians is how much and where, rather than a simple statement on the presence or absence of abnormalities. The authors present a study in which the results obtained with a semiautomatic, multispectral segmentation technique are quantitatively compared to manually delineated regions. The core of the semiautomatic image analysis system is a supervised artificial neural network classifier augmented with dedicated preand postprocessing algorithms, including anisotropic noise filtering and a surface-fitting method for the correction of spatial intensity variations. The study was focused on the quantitation of white matter lesions in the human brain. A total of 36 images from six brain volumes was analyzed twice by each of two operators, under supervision of a neuroradiologist. Both the intra- and interrater variability of the methods were studied in terms of the average tissue area detected per slice, the correlation coefficients between area measurements, and a measure of similarity derived from the kappa statistic. The results indicate that, compared to a manual method, the use of the semiautomatic technique not only facilitates the analysis of the images, but also has similar or lower intra- and interrater variabilities.
Artifacts in MRI: description, causes, and solutions
- Wesbey G
Wesbey G. Artifacts in MRI: description, causes, and solutions. Clinical
magnetic resonance imaging. 1996:88-144.
The challenges of managing glioblastoma multiforme in developing countries: a trade-off between cost and quality of care
- Salem