Intralesional Necrosis Research Articles

Computed tomography-based contrast features for distinguishing extra-gastrointestinal stromal tumors from intra-abdominal fibromatosis.

This study aims to define the computed tomography (CT) criteria that distinguish extra-gastrointestinal stromal tumors (eGISTs) from intra-abdominal fibromatosis (IAF). Retrospective analysis was conducted on CT images obtained from 31 pathologically confirmed cases, including 17 cases of eGISTs and 14 of IAF. Various parameters [e.g., lesion location, contour characteristics, border delineation, enhancement patterns, presence of intralesional necrosis, vessels, air, fat, and hemorrhage, the long diameter (LD), LD/short diameter (SD) ratio, and volume (LD × SD × height diameter)] were meticulously evaluated. In addition, the degree of enhancement during arterial and portal venous phases and the lesion-to-aorta CT attenuation ratio during both phases were quantified. Statistical analysis was performed using Fisher's exact test, the Student's t-test, and the receiver operating characteristic curve to identify significant CT criteria. Sensitivity and specificity assessments were conducted for single and combined CT criteria. Significant differentiators between eGISTs and IAF include non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, and absence of intralesional fat, with LD exceeding 9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3 (P < 0.05). A combination of seven or more of these criteria yielded a specificity of 100%. Ten distinct CT criteria have been identified to distinguish eGISTs from IAF, notably encompassing non-mesenteric localization, irregular contour, well-defined borders, heterogeneous enhancement, presence of intralesional necrosis and vessels, absence of intralesional fat, LD >9.6 cm, an LD/SD ratio >1.22, and volume surpassing 603.3 cm3. The current findings establish CT criteria to distinguish eGISTs from IAF in a clinical setting.

Multiparametric Characterization of the DSL-6A/C1 Pancreatic Cancer Model in Rats.

The DSL-6A/C1 murine pancreatic ductal adenocarcinoma (PDAC) tumor model was established in Lewis rats and characterized through a comprehensive multiparametric analysis to compare it to other preclinical tumor models and explore potential diagnostic and therapeutical targets. DSL-6A/C1 tumors were histologically analyzed to elucidate PDAC features. The tumor microenvironment was studied for immune cell prevalence. Multiparametric MRI and PET imaging were utilized to characterize tumors, and 68Ga-FAPI-46-targeting cancer-associated fibroblasts (CAFs), were used to validate the histological findings. The histology confirmed typical PDAC characteristics, such as malformed pancreatic ductal malignant cells and CAFs. Distinct immune landscapes were identified, revealing an increased presence of CD8+ T cells and a decreased CD4+ T cell fraction within the tumor microenvironment. PET imaging with 68Ga-FAPI tracers exhibited strong tracer uptake in tumor tissues. The MRI parameters indicated increasing intralesional necrosis over time and elevated contrast media uptake in vital tumor areas. We have demonstrated that the DSL-6A/C1 tumor model, particularly due to its high tumorigenicity, tumor size, and 68Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.

Prediction of Pathological Risk Stratification using Computed Tomography Features in Gastrointestinal Stromal Tumours: A Retrospective observational Study

Introduction: Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours of gastrointestinal tract. A high postsurgical recurrence and metastatic rate have created a need for a presurgical risk profile identification system. Aim: To assess the association between morphological Computed Tomography (CT) parameters with the pathological risk profile and analyse which CT features can predict the risk grading of GISTs. Materials and Methods: This was a retrospective cohort study based on imaging and histopathological data of 26 patients with pathologically proven GISTs presenting to the Department of Radiodiagnosis of a tertiary hospital in the northern Indian Himalayan foothills over a period of five years from July 2018 to June 2023. CT imaging features including size, growth pattern, margins, enhancement, calcifications, necrosis, intralesional haemorrhage, enlarged feeding vessels, direct organ invasion, and associations such as ascites and lymphadenopathy were studied. All lesions were classified as per Miettinen risk classification into no risk, very low-risk, low, moderate, and high-risk lesions. Analysis was done by the Chi-square test. Predictive analysis was carried out by computing the odds ratio and performing regression analysis on significantly associated imaging features. Results: Out of 26 patients, the study group comprised 16 males (61.54%) and 10 females (38.46%). The most common decade of presentation was the 6th decade with the mean age of presentation being 55.81±4.23 years. Twelve patients were grouped under intermediate to high-risk grading. Lesion size &gt;5 cm (p-value=0.0171, OR=19.12), ill-defined margins (p-value=0.0048, OR=18.33), intralesional necrosis (p-value=0.0053, OR=19.8), and enlarged feeding vessels (p-value=0.012, OR=21.27) were identified as imaging features with significant association and predictive ability for high-risk lesions. The strongest predictive ability for a high-risk profile was shown by ill-defined margins (R2 =0.381) and intralesional necrosis (R2 =0.3287). Conclusion: A preoperative Contrast Enhanced Computed Tomography (CECT) assessment provides a comprehensive imaging profile for GISTs as well as a fair accuracy of risk profile prediction via various singular and clustered morphological parameters.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic insulinoma: A single-center experience

Background/objectivesInsulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as a minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. MethodsThis is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success (i.e., complete mass ablation), adverse event rate and severity, clinical and radiologic outcomes (i.e., symptom remission with a normal concentration of blood glucose, and the presence of intralesional necrosis), and post-procedural follow-up were assessed. ResultsA total of 10 patients (mean age: 67.1 ± 10.1years; F:M 7:3) were included. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success and clinical remission were achieved in 100% of patients. Only one (10%) patient was successfully treated with two RFA sessions. Two procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain. No major complications were observed. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). After a median follow-up of 19.5 (range12–59) months, symptom remission and persistent euglycemia were assessed in all the patients. ConclusionsData from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas in patients unwilling or unable to undergo surgery with medium-term efficacy.

Radiologic-pathologic correlation in breast cancer: do MRI biomarkers correlate with pathologic features and molecular subtypes?

BackgroundBreast cancer (BC) includes different pathological and molecular subtypes. This study aimed to investigate whether multiparametric magnetic resonance imaging (mpMRI) could reliably predict the molecular status of BC, comparing mpMRI features with pathological and immunohistochemical results.MethodsThis retrospective study included 156 patients with an ultrasound-guided biopsy-proven BC, who underwent breast mpMRI (including diffusion-weighted imaging) on a 3-T scanner from 2017 to 2020. Histopathological analyses were performed on the surgical specimens. Kolmogorov–Smirnov Z, χ2, and univariate and multivariate logistic regression analyses were performed.ResultsFifteen patients were affected with ductal carcinoma in situ, 122 by invasive carcinoma of no special type, and 19 with invasive lobular carcinoma. Out of a total of 141 invasive cancers, 45 were luminal A-like, 54 luminal B-like, 5 human epidermal growth factor receptor 2 (HER2) positive, and 37 triple negative. The regression analyses showed that size < 2 cm predicted luminal A-like status (p = 0.025), while rim enhancement (p < 0.001), intralesional necrosis (p = 0.001), peritumoural oedema (p < 0.001), and axillary adenopathies (p = 0.012) were negative predictors. Oppositely, round shape (p = 0.001), rim enhancement (p < 0.001), intralesional necrosis (p < 0.001), and peritumoural oedema (p < 0.001) predicted triple-negative status.ConclusionsmpMRI has been confirmed to be a valid noninvasive predictor of BC subtypes, especially luminal A and triple negative. Considering the central role of pathology in BC diagnosis and immunohistochemical profiling in the current precision medicine era, a detailed radiologic-pathologic correlation seems vital to properly evaluate BC.

Single institutional outcomes of whole brain radiotherapy for metastatic melanoma brain metastases

BackgroundThe management of melanoma with brain metastases (MBM) is increasingly complex, especially given recent improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a longstanding radiotherapy technique for which reported patient outcomes and experiences are limited. We sought to report our institutional outcomes for MBM patients receiving WBRT and assess whether other clinical factors impact prognosis.MethodsA retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000 to 2018 treated with WBRT, with or without other systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), distant failure-free survival (DFFS), local failure-free survival (LFFS), and progression-free survival (PFS) were assessed. Data on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits, was also captured.Results63 patients with MBM were ultimately included in our study. 69% of patients had 5 or more brain metastases at the time of WBRT, and 68% had extracranial disease. The median dose of WBRT was 30 Gy over 10 fractions. Median follow-up was 4.0 months. Patients receiving WBRT had a median OS of 7.0 months, median PFS of 2.2 months, median DFFS of 6.1 months, and median LFFS of 4.9 months. Performance status correlated with OS on both univariate and multivariable analysis. BRAF inhibitor was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07–0.79, p = 0.019), and this effect extended to multivariable analysis as well. Post-WBRT intralesional hemorrhage decreased DFFS on both univariate and multivariable analysis. Of patients with post-treatment brain scans available, there was a 16% rate of radionecrosis, 32% rate of hemorrhage, and 19% rate of memory deficits.ConclusionsOutcomes for MBM patients receiving WBRT indicate that WBRT remains an effective treatment strategy to control intracranial disease. Treatment-related toxicities such as intralesional hemorrhage, necrosis, or neurocognitive side effects are limited. With continued innovations in WBRT technique and systemic therapy development, MBM outcomes may continue to improve. Further trials should evaluate the role of WBRT in the modern context.

Adrenal metastases: early biphasic contrast-enhanced CT findings with emphasis on differentiation from lipid-poor adrenal adenomas

To evaluate the accuracy of unenhanced attenuation and early biphasic contrast-enhanced computed tomography (CT) in differentiating adrenal metastases (AMs) from lipid-poor adrenal adenomas (AAs). This retrospective study included 37 patients with 50 AMs and 86 patients with 89 lipid-poor AAs. Quantitative data including the longest diameter (LD), the shortest diameter (SD), LD/SD ratio, CT attenuation values (CTu, CTa, CTv), degree of enhancement (DEAP, DEPP, DEpeak, APW, RPW), and peak enhanced/unenhanced (PE/U) CT attenuation ratio were obtained. Qualitative data including enhancement pattern, location, shape, the presence of calcification or haemorrhage, and intra-lesion necrosis were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated. The PE/U ratio (≤1.25), CTu (≥32.2 HU), DEpeak (≤43.15 HU), DEPP (≤37.65 HU), presence of intralesional necrosis, location (bilateral adrenal glands), and irregular shape were significant variables for differentiating AMs from lipid-poor AAs (p<0.05). Among them, PE/U ratio (≤1.25) was of greater value in differentiating the two adrenal diseases, with sensitivity, specificity, area under the receiver operating curve (ROC) curve (AUC) of 92%, 84%, 0.933, respectively. When at least any three of above criteria were combined, the sensitivity, specificity, PPV, and NPV for diagnosing AMs were 88%, 93%, 88%, and 88%, respectively. These seven CT criteria are conducive to differentiate AMs from lipid-poor AAs. Early biphasic contrast-enhanced CT is a high-efficient and practical imaging tool in differentiating them.

Can MRI Biomarkers Predict Triple-Negative Breast Cancer?

The purpose of this study was to investigate MRI features of triple-negative breast cancer (TNBC) compared with non-TNBC, to predict histopathological results. In the study, 26 patients with TNBC and 24 with non-TNBC who underwent multiparametric MRI of the breast on a 3 T magnet over a 10-months period were retrospectively recruited. MR imaging sets were evaluated by two experienced breast radiologists in consensus and classified according to the 2013 American College of Radiology (ACR) BI-RADS lexicon. The comparison between the two groups was performed using the Chi-square test and followed by logistic regression analyses. We found that 92% of tumors presented as mass enhancements (p = 0.192). 41.7% of TNBC and 86.4% of non-TNBC had irregular shape (p = 0.005); 58.3% of TNBC showed circumscribed margins, compared to 9.1% of non-TNBC masses (p = 0.001); 75% of TNBC and 9.1% of non-TNBC showed rim enhancement (p < 0.001). Intralesional necrosis was significantly associated with TNBC (p = 0.016). Rim enhancement and intralesional necrosis risulted to be positive predictors at univariate analysis (OR = 29.86, and 8.10, respectively) and the multivariate analysis confirmed that rim enhancement is independently associated with TNBC (OR = 33.08). The mean ADC values were significantly higher for TNBC (p = 0.011). In conclusion, TNBC is associated with specific MRI features that can be possible predictors of pathological results, with a consequent prognostic value.

A scoring model for radiologic diagnosis of gastric leiomyomas (GLMs) with contrast-enhanced computed tomography (CE-CT): Differential diagnosis from gastrointestinal stromal tumors (GISTs)

ObjectivesTo investigate CT findings and develop a diagnostic score model to differentiate GLMs from GISTs. MethodsThis retrospective study included 109 patients with pathologically confirmed GLMs (n = 46) and GISTs (n = 63) from January 2013 to August 2018 who received CE-CT before surgery. Demographic and radiological features was collected, including lesion location, contour, presence or absence of intralesional necrosis and ulceration, growth pattern, whether the tumor involved EGJ, the long diameter (LD) /the short diameter (SD) ratio, pattern and degree of lesion enhancement. Univariate analyses and multivariate logistic regression analyses were performed to identify independent predictors and establish a predictive model. Independent predictors for GLMs were weighted with scores based on regression coefficients. A receiver operating characteristic (ROC) curve was created to determine the diagnostic ability of the model. Overall score distribution was divided into four groups to show differentiating probability of GLMs from GISTs. ResultsFive CT features were the independent predictors for GLMs diagnosis in multivariate logistic regression analysis, including esophagogastric junction (EGJ) involvement (OR, 367.9; 95 % CI, 5.8–23302.8; P = 0.005), absence of necrosis (OR, 11.9; 95 % CI, 1.0−138. 1; P = 0.048) and ulceration (OR, 151.9; 95 % CI, 1.4–16899.6; P = 0.037), degree of enhancement (OR, 9.3; 95 % CI, 3.2–27.4; P < 0.001), and long diameter/ short diameter (LD/SD) ratio (OR,170.9; 95 % CI, 8.4–3493.4; P = 0.001). At a cutoff of 9 points, AUC for this score model was 0.95, with 95.65 % sensitivity, 79.37 % specificity, 77.19 % PPV, 96.15 % NPV and 86.24 % diagnostic accuracy. An increasing trend was showed in diagnostic probability of GLMs among four groups based on the score (P < 0.001). ConclusionsThe newly designed scoring system is reliable and easy-to-use for GLMs diagnosis by distinguishing from GISTs, including EGJ involvement, absence of ulceration and necrosis, mild enhancement and high LD/SD ratio. The overall score of model ranged from 1 to 17 points, which was divided into 4 groups: 1–7 points, 7–10 points, 10–13 points and 13–17 points, with a diagnostic probability of GLMs 0%, 45 %, 83 % and 100 %, respectively.

Histologically-Proven Efficacy of Bland Embolization in a Patient with Net Liver Metastasis.

We present a case of 57-year-old patient with three liver metastases from a primary neuroendocrine duodenal tumor, who underwent bland embolization with excellent response to therapy, followed by surgical resection. The purpose of our case report is to describe the histological characteristics of tumoral response to therapy after bland embolization focusing on intralesional necrosis and microsphere distribution.

Epidemiological and morphological analysis of feline injection site sarcomas.

Feline injection site sarcomas (FISS) are malignant neoplasms of mesenchymal origin which arise in sites of injections in cats. The prevalence is estimated between 1 in 1000 and 1 in 10 000 vaccinations in the United Kingdom. The aim of this study was to estimate the incidence of FISS in Poland and to analyse clinical aspects and histological and cytological features of injection site sarcomas. In our study the prevalence of FISS was 0.16% (16 FISS on 10.000 of cats) in feline patients in one of a veterinary surgery which conducts the general practice and 85 on 10.000 cats in a practice focused on veterinary oncology. The most typical microscopic features of FISS found in the present analysis were: the presence of perilesional scarring and inflammation, aggregates of lymphocytes at the tumour periphery, moderate but usually marked cellular pleomorphism and intralesional necrosis. The most typical cytologic features of FISS found in present study were: the presence of neutrophils, marked cellular pleomorphism, the presence of lymphocytes and macrophages, the presence of extremely large nuclei in the neoplastic cells, and high sample cellularity.

Intra-abdominal fibromatosis: Differentiation from gastrointestinal stromal tumour based on biphasic contrast-enhanced CT findings

To identify the computed tomography (CT) criteria that differentiate intra-abdominal fibromatosis (IAF) from gastrointestinal stromal tumour (GIST). CT images of 34 pathologically proven cases of IAF (n=15) and GIST (n=19) were retrospectively reviewed. Location, contour, border, enhancement pattern, presence of necrosis, vessels, and air within the lesion were analysed. Long diameter (LD), short diameter (SD), LD/SD ratio, degree of enhancement, and lesion/aorta (L/A) CT attenuation ratio were measured and calculated. Significant CT criteria were identified using Fisher's exact test, grouped t-test, and receiver operating characteristic (ROC) curve. Sensitivity and specificity values were calculated when single or multiple CT criteria were used. Extra-gastrointestinal location, ovoid or irregular contour, homogeneous enhancement, absence of intra-lesional necrosis, lower degree of enhancement, and L/A CT attenuation ratio differentiated IAF from GIST (p<0.05). When any three of these eight criteria were combined, the sensitivity and specificity for diagnosing IAF were 100% (15 of 15) and 89.5% (17 of 19), respectively. The following eight CT criteria are helpful to differentiate IAF from GIST: extra-gastrointestinal location, ovoid or irregular contour, homogeneous enhancement, absence of intra-lesional necrosis, a degree of enhancement of less than 40.5HU in the arterial phase versus 46.5HU in the portal venous phase, and an L/A CT attenuation ratio <0.315 in the arterial phase versus 0.525 in the portal phase.

Head and neck inflammatory myofibroblastic tumor (IMT): Evaluation of clinicopathologic and prognostic features

Owing to rarity and awareness deficiency towards inflammatory myofibroblastic tumor (IMT), we sought to review on its clinicopathological features; arising awareness to achieve early diagnosis; exploring prognostic factors and then establishing a treatment protocol. Retrospective study was performed on patients with histological proven IMT between January 2003 and December 2010. Their demographic data, clinical and histological presentations were recorded. Overall survival (OS) and progression-free-survival (PFS) were estimated via Kaplan-Meier method. Cox regression model was applied to determine the significant of prognostic factors. Logistic regression model was established to predict the probability of relapse. A total of 28 patients. Five-year PFS was 65%. Surgical margins primarily and independently determined the survival, followed by size, pseudocapsule of the lesion, intra-lesional necrosis and lastly Ki-67 and ALK overexpression. Logistic model in prediction of relapse was established, with the formula as probability of relapse = 1/(1 + e(-z)) where e = exponential function, z = constant value (3.9) + B*margin + B*size + B*immunohistochemical expression + B*pseudocapsule + B*intra-lesional necrosis. Immunohistochemical overexpression was significant if Ki-67 was strongly expressed with a conditioned ALK overexpression simultaneously. Staining intensity must be at least moderate for those ALK nuclear staining was less than 25%. Weak ALK staining intensity is only significant if nuclear staining was more than 25%. Diagnosis of IMT is achieved via exclusion. Radical resection and obtaining negative margins remains the mainstay of treatment. Both high and moderate-risk groups required post-operative radiotherapy. In low-risk group, post-operative radiotherapy was recommended if the lesion is larger than 5 cm in diameter with a conditioned ALK & Ki-67 overexpression.

Early MRI response monitoring of patients with advanced hepatocellular carcinoma under treatment with the multikinase inhibitor sorafenib

BackgroundNew therapeutic principles in clinical oncology require the adjustment of response criteria to govern therapy decisions. For advanced hepatocellular carcinoma (HCC) a new era has recently begun by the approval of the multikinase inhibitor sorafenib. As a unique feature, HCC usually develops in a diseased liver and current imaging technologies employing classical response criteria have not been prospectively evaluated for this new treatment.MethodsMRI signal patterns were assessed in 21 advanced HCC patients receiving sorafenib. MRI was performed at baseline and in short-term intervals thereafter. Signal changes under therapy on T1WI, T2WI and post-gadolinium images including necrosis volume and its ratio to the entire tumor volume were compared to baseline imaging. To assess the association between the categorical variables, Fisher's exact tests were applied for a statistical analysis. Survey time ranged from 2–65 weeks, and a total of 39 target lesions were evaluated.ResultsSignal abnormalities during sorafenib therapy were disclosed by T1WI and T2WI in 15/21 patients. The predominant tumor signal change was hyperintensity on both T1WI and T2WI. Interestingly, most patients developed MRI signal changes within 4 weeks of therapy; in contrast, two non-responders did not show any signal alteration at follow-up. Under therapy, 16/21 patients presented with new or progressive necrosis, whereas 7 patients achieved temporarily >75% tumor necrosis under sorafenib. Significantly associated MRI variables were increase in T1WI signal and tumor necrosis (p = 0.017) as well as increase of tumor necrosis with an elevated ratio of necrotic to vital tumor areas (p = 0.002). Remarkably, some (3/13) of the patients developing necrotic tumor areas showed a relevant (>20%) increase in tumor volume, which should be considered in the assessment of imaging studies.ConclusionAs sorafenib induces early intralesional necrosis with profound changes in T1WI/T2WI MRI signal intensities and measurable necrotic tumor areas in most HCC patients, early MRI-based evaluation could pave the way for its rationale and cost-effective application.

The Histologic and Epidemiologic Bases for Prognostic Considerations in Canine Melanocytic Neoplasia

The laboratory records from 384 dogs with a diagnosis of either melanoma or melanocytoma were selected for study. Significant negative determinants of patient survival for melanocytic tumors were: 1) metastasis, 2) mitotic index (MI), 3) nuclear atypia, 4) tumor score, 5) increasing size/volume, 6) the presence of deep inflammation, and/or 7) intralesional necrosis. In addition to these attributes, age was a significant determinant for tumors of the skin. For the feet and lips, 8) age and 9) junction activity negatively impacted survival. Mathematic models were constructed based on these significant determinants to predict the postsurgical outcome of melanocytic neoplasia. Melanocytic oral neoplasms comprised 19% (73/384) of the neoplasms; 92% of these were classified as malignant in the biopsy report, but malignant behavior (i.e., metastasis or recurrence) was observed in only 59% of cases. The prognostic model for oral tumors based on nuclear atypia provided the most accurate (89%) prediction of overall behavior. Melanocytic tumors of the feet and lips were also 19% (73/384) of the total population. Seventy-four percent were reported malignant, whereas only 38% actually demonstrated malignant behavior. The prognostic models based on both MI or nuclear atypia had an overall correct behavioral classification of 81%. Melanocytic tumors in the skin comprised 59% (227/384) of study specimens. Although 39% were reported as malignant, only 12% exhibited malignant behavior. A satisfactory predictive model that employed MI could not be constructed, but one using nuclear atypia gave an overall correct classification in 93.3% of the cases.

Magnetic resonance imaging of soft tissue tumors.

This article outlines the ability of MR imaging in staging, grading, tissue characterization, and posttherapeutic surveillance of soft tissue tumors. Well-known staging parameters, such as extent, relationship with adjacent structures, and detection of intralesional necrosis, are used in the MR protocol for locoregional staging. Bone scintigraphy and high-resolution CT scan of the lungs are best methods for ruling out metastatic spread. A variety of (solitary or combinations of) grading parameters are described in the radiological literature. The role of MR imaging is to afford recognition of these lesions that need further aggressive work-up, excluding all others. Despite controversial reports, the definite role of MR imaging in grading of soft tissue tumors seems to become established. As for grading, a lot of individual imaging characteristics used for tissue characterization have low sensitivity, but combinations of parameters (age, site, signal intensities) are more useful and often allow to predict a specific diagnosis or to narrow down the list of differential diagnoses. Local recurrences of soft tissue tumors are frequent and can be detected accurately by an easy-to-use MR algorithm.

Permanent I-125 brain stem implants in children.

Between 1988 and 1997, 28 children have had iodine-125 implants for CNS tumors performed in our institution. Ten had stereotactic implantation in the brain stem region, and nine had the diagnosis of brain stem glioma (8 diffuse pontine, 1 midbrain tumor). Their ages ranged from 1.8 to 12 years. All patients had histological confirmation of malignancy (7 high-grade glioma, 2 low-grade glioma, 1 PNET). Diffuse pontine glioma patients received external beam radiation (50 Gy) followed by a fractionated stereotactic boost of 3 Gyx4 fractions. After 4-6 weeks, patients were reevaluated for stereotactic interstitial I-125 therapy. The planned implant dose was 82.9 Gy to the enhancing tumor (4 cGy per h). Preliminary results indicated that no surgical complications were associated with the catheter placement. Four patients have died (7-9 months from diagnosis) and four patients remain alive (5-38 months from diagnosis, median 10 months). Two autopsies confirmed the presence of progressive glioblastoma multiforme and intralesional necrosis. In one patient who received an implant alone for midbrain LGA, necrosis without tumor was found on biopsy after 36 months. He was successfully treated with hyperbaric oxygen therapy. The implementation of permanent I-125 implants appears to have a role in the management of pediatric CNS malignancy. This study confirms the results of previous reports regarding the safety of stereotactic interstitial brachytherapy in the brain stem. Tumor control for patients with high-grade brain stem glioma remains poor even with high focal radiation doses.

Hyperfractionated radiotherapy for diffuse intrinsic brain stem tumors in children.

Over the past decade, the principle focus of clinical research in children with diffuse intrinsic brain stem tumors has been on the use of hyperfractionated radiotherapy because of the predominantly local pattern of failure and the evidence for a dose-response relationship with conventional radiotherapy that might suggest an advantage to the use of the higher total radiation doses that can be given using a hyperfractionated schedule. Since 1984, large numbers of children have been accrued to a series of phase I/II studies testing escalating doses of hyperfractionated radiotherapy. At the lowest dose levels of 64.8 and 66 Gy, results were not better than those seen after conventional treatment and no unusual or unexpected toxicity was observed. At intermediate dose levels of 70.2 and 72 Gy there was some suggestion of improved efficacy. At the highest dose level of 75.6 and 78 Gy there were no further gains in efficacy and complications of treatment including steroid dependency and intralesional necrosis were observed with greater frequency. The intermediate dose level was therefore considered to be associated with the best therapeutic ratio and the value of hyperfractionated radiotherapy at this dose level is being tested by the Pediatric Oncology Group in a randomized phase III study that will be completed soon.

Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: A pediatric oncology group study

Purpose : In September 1984, the Pediatric Oncology Group began accrual to a Phase I/II study designed to assess the efficacy and toxicity of sequentially escalated doses of hyperfractionated (twice daily) radiotherapy in children wit-h poor-prognosis brain stem tumors. Pediatric Oncology Group Study #849closed in June 1990 with a total of 136 patients on study. We report here the outcome of patients treated atthe third and final dose level (75.6 Gy), and compare the results to those obtained at the 66 and 70.2 Gy dose levels. Methods and Materials : Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the midbrain, pons or medulla. Histological confirmation of diagnosis was not mandatory provided that the clinical and radiological findings were typical for brain stem glioma. Treatment consisted of radiotherapy delivered to local fields. At the third dose level, fraction sizes of 1.26 Gy were given twice dally, with a minimum interfraction interval of 6 hr to a dose of 75.6 Gy in 60 fractions over 6 weeks. Between 5 89 and 6 90 , 41 patients were accrued to the study. Two were excluded from analysis leaving 39 evaluable patients, 21 male and 19 female, whose ages ranged from 3 to 15 years (median 7.5 years). Results : Following treatment, neurological improvement was reported in 30/39 (77%) of the patients. On central review of imaging studies in 29 patients, one patient was found to have had a complete response to radiotherapy, five a partial (> 50% response), and only three had non-responding or progressive disease. The median time to disease progression was 7 months; median survival time was 10 months; survival at 1 year was 39.9% (SE 8.3%) and at 2 years, 7% (SE 4.8%). The pattern of failure was local in all patients; in addition six had evidence of leptomeningeal seeding. Morbidity of treatment included an enhanced skin reaction (21%), otitis media and/or externa (26%) and steroid use > 3 months (62%). Intralesional necrosis was a frequent finding (45%) on imaging studies performed at a median time of 6 weeks post treatment. Conclusion : The results of treatment in terms of progression-free survival and overall survival are not significantly different (at p = .55 and p = .46, respectively) from those obtained at the two previous dose levels. There is no evidence that higher doses of hyperfractionated radiotherapy given as in this study improve the outlook of patients with poor-risk brain stem gliomas.

Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cgy dose level of pediatric oncology group study #8495

Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.