True Tumor Recurrence Research Articles

NCMP-12. PREVALENCE OF RADIONECROSIS IN RECURRENT GLIOBLASTOMA

Abstract INTRODUCTION Glioblastoma (GBM) standard treatment consists of maximum and safe surgical resection, followed by radiation therapy in combination with temozolomide. Some patients show radiological and/or clinical deterioration soon after radiotherapy treatment. Early MRI changes, in the first 3 months following radiation is considered pseudo-progression. After this initial period, changes are considered as tumor recurrence. However, cases of early radiological deterioration have been related to radionecrosis. When tumor progression is suspected on imaging, it may causes treatment withdrawal or change. Therefore, for a certain percentage of patients, effective treatment could be abandoned in the presence of radionecrosis. METHODS The aim of the study is to assess the prevalence of radionecrosis at the Hôpital de l'Enfant-Jésus. This is a retrospective, observational case-control study evaluating recurrent GBM patients who underwent a second resection surgery. RESULTS The charts of 110 GBM patients with second resection were retrospectively reviewed (men: 62%, mean age: 58.3 years). Among these patients, we observed 87 cases of GBM recurrence as compared to 23 cases of radionecrosis (21%). No statistically significant difference was observed between the two groups regarding demographics, survival, Karnofsky performance status, type of surgery and treatments received. However, in the radionecrosis group, decreases in time between the 2 surgeries (55.3 vs. 24.3 weeks, p = 0.006) and in the number of cycles of chemotherapy received (5.7 vs. 3.7 weeks, p = 0.004) were observed as compared to GBM group. CONCLUSIONS This study characterizes demographically the patients with second surgery for suspicion of GBM in order to better adapt the treatments. Clinical and radiological data could not differentiate radionecrosis from true tumor recurrence or progression. A prospective study will be carried out as a second step, in order to determine radiological or molecular factors that could predict the presence of radionecrosis.

Multimodality MRI Radiomics Based on Machine Learning for Identifying True Tumor Recurrence and Treatment-Related Effects in Patients with Postoperative Glioma.

Conventional magnetic resonance imaging (MRI) features have difficulty distinguishing glioma true tumor recurrence (TuR) from treatment-related effects (TrE). We aimed to develop a machine-learning model based on multimodality MRI radiomics to help improve the efficiency of identifying glioma TuR. A total of 131 patients were enrolled and randomly divided into the training set (n=91) and the test set (n=40). Radiomic features were extracted from the postoperative enhancement (PoE) region and edema (ED) region from four routine MRI sequences. After analyses of Spearman's rank correlation coefficient, and least absolute shrinkage and selection operator, the key radiomic features were selected to construct support vector machine (SVM) and k-nearest neighbor (KNN) models. Decision curve analysis (DCA) and receiver operating characteristic (ROC) curves were used to analyze the performance. The PoE model had a significantly higher area under curve (AUC) than the ED model (p<0.05). Among the models constructed with a single sequence, the model using PoE regional features from CE-T1WI was superior to other models, with an AUC of 0.905 for SVM and 0.899 for KNN. In multimodality models, the PoE model outperformed the ED model with an AUC of 0.931 for SVM and 0.896 for KNN. The multimodality model, which combined routine sequences and the whole regional features, showed a slightly better performance with an AUC of 0.965 for SVM and 0.955 for KNN. Decision curve analysis showed the good clinical utility of multimodal radiomics models. Multimodality radiomics can identify glioma TuR and TrE, potentially aiding clinical decision-making for individualized treatment. And edematous regions may provide useful information for recognizing recurrence. 2021.04.15, No:2020039.

Pseudoprogression and pseudoresponse according to MRI data after radiosurgical treatment of glioblastoma using metronidazole

Aims: to determine response rates to radiosurgical treatment of patients with glioblastoma using hypoxic radiosensitizers based on MRI data to improve diagnosis of true tumor recurrence, or true response to treatment from pseudoprogression and pseudoresponse. Methods. From 106 patients with glioblastoma treated with radiosurgery, we compared the group with the use of radiosensitizers and the control group without it, focusing on the differential diagnosis of pseudoprogression and pseudoresponse from true tumor recurrences and response to treatment, comparing the success of treatment in terms of recurrence-free and overall survival. Results. From the total number of treated patients, signs of pseudoprogression were observed in 30 patients (34.09%) in the period from 3 to 6 months after SRH. A pseudoresponse was observed in 4 patients (4.54%) during the first week, in two patients on the third day, and in two patients on the fifth day after SRH using the hypoxic radiosensitizer metronidazole. The value of ADC in the zone of intermediate hypoxia was important not only for differential diagnosis of pseudoprogression and pseudoresponse from true progression and response, but also for determining predictors of treatment success, for example, an increase in ADC from 0.9-1.0x10-3mm2/s to 1.1 -1.2x10-3mm2/s one week after SRH with radiosensitization was not only an indicator of true response, but also a predictor of relapse-free survival rates over 10 months, and overall - 20 months in the main group. Conclusions. Indicators of perfusion, diffusion and BOLD programs help to carry out differential diagnosis of pseudoprogression, pseudoresponse and true relapses and tumor response to radiosurgical treatment, the study of ADC indicators, which, in addition to high sensitivity and specificity, are predictors of radiosurgical treatment of glioblastoma, deserves special importance.

Value of diffusion-weighted images in diagnosis of locoregionally recurrent rectal tumors

IntroductionTo assess the value of referring to Diffusion-weighted images in evaluation of T2-weighted images of patients clinically suspicious of locoregional rectal cancer recurrence. MethodsAfter ethics committee approval and informed consent were obtained, 37 consecutive patients (male/female of 22/15; mean age 56 ± 13.5 SD) clinically suspicious of recurrent rectal tumor were prospectively included in the study over a two-year period. T2-weighted images of the patients were reviewed and the results were recorded. Right after that, the corresponding DWI images were provided for the radiologist and new ratings were given to the patients after taking into account the DWI findings. Finally, the patients underwent tissue biopsy. Receiver Operating Characteristic (ROC) analysis was performed, and Area Under the Curve (AUC) of the “T2-weighted alone” and “T2-weighted + DWI” methods were calculated and compared. Results“T2-weighted alone” and “T2-weighted + DWI” methods had an AUC of 0.64 (95% CI 0.47 to 0.79) and 0.75 (95% CI 0.58 to 0.88), respectively. The Difference between the two AUCs was 0.11 (P = 0.16). In the subgroup of patients having equivocal ratings in T2-weighted images, DWI images correctly identified 81% (13/16) of patients with true tumor recurrence and 66% (8/12) of patients without recurrence. ConclusionOur results suggest that referring to DWI does not significantly change the overall diagnostic performance of T2-weighted images. However, DWI is of great value in evaluation of the subgroup of patients with equivocal findings in T2-weighted images. Studies with larger sample sizes are needed to confirm these findings. Implications for practiceWhen T2-weighted images are equivocal, DWI images may be helpful in evaluation of patients with suspected locoregional recurrence of rectal tumor.

Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors.

ObjectiveWe evaluated tumor recurrence and regrowth rates following endoscopic transnasal transsphenoidal (TNTS) surgical removal in a consecutive series of clinically nonfunctioning pituitary adenomas (CNFTs).DesignRetrospective chart review of clinical, biochemical, and sellar MRI findings in all TNTS surgeries in patients with CNFT, performed by a single surgeon, between 2008 and 2015 (n = 280).PatientsNinety-three patients met eligibility criteria, with complete clinical, biochemical, and imaging follow-up for a 3-year minimum.ResultsOf 85 patients who were not irradiated, 3-month postsurgical MRI demonstrated no residual tumor in 58 of 85 (68.2%), equivocal findings in 12 of 85 (14.1%), and definite residual tumor in 15 of 85 (17.6%) patients. Six of 85 (7.1%) demonstrated tumor regrowth by 3 years, and 2 further patients demonstrated true tumor recurrence at 3 and 6 years after surgery, respectively, for a total recurrence rate of 9.4% (8 of 85). Eight of the 93 patients were irradiated between 3 months and 4 years after pituitary surgery. In 3 patients with tumor regrowth, 2 exhibited residual tumor and 1 had no residual findings at the 3-month postoperative imaging. Overall, Ki-67 labeling index or Knosp grading did not predict recurrence.ConclusionTumor recurrence at 3 years was low (1 of 58; 1.7%) if the 3-month postoperative MRI showed no residual tumor. The findings support a less frequent imaging schedule for this group. Patients with definite residual tumor visible at 3 months harbor the greatest risk for tumor growth, but regrowth does not occur in all patients (6 of 15; 40%).

Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-L-Tyrosine PET.

PET/CT using O-(2-[F]fluoroethyl)-L-tyrosine (F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. Irrespective of the analytical approach, F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers.

Recurrent brain tumor versus radiation necrosis; can dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging differentiate?

BackgroundAssessment of treatment response in patients with a brain tumor is paramount, as true tumor recurrence and radiation necrosis are similar looking on conventional MRI. PurposeTo evaluate the role of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging in the differentiation between recurrent brain tumors and radiation necrosis. Material and MethodsTwenty patients with a history of operated primary brain tumors and postoperative radiotherapy with or without chemotherapy were enrolled in this prospective study having conventional MRI findings of enhancing lesion suspicious of being recurrence or radiation necrosis. All patients were examined by DSC-perfusion MRI. Definitive diagnosis was reached through either subsequent surgical biopsy or follow up over 6-12 months. ResultsFifteen patients (75%) were diagnosed as tumor recurrence and 5 patients as radiation necrosis (25%). The relative cerebral blood volume (rCBV) and relative peak height (rPH) were significantly higher (P < 0.05) in recurrent tumors than in radiation necrosis lesions. The rCBV and rPH thresholds in differentiating between them were 1.8 and 1.22 respectively with 87%, 93% sensitivity and 100% specificity for each respectively. ConclusionsDSC-perfusion MRI is a valuable non-invasive tool besides conventional MRI whenever available to differentiate between radiation injury changes and tumor recurrence.

Advances in exosome-related biomarkers for glioblastoma: Basic research and clinical application

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. The median survival rate of GBM patients is approximately 14 months and tumor recurrence is almost inevitable. With the increased use of immunotherapy, immune response and edema found on posttreatment magnetic resonance imaging (MRI) may be misinterpreted as tumor progression. Distinguishing the true radiographic progression from pseudo-progression by MRI is often difficult. Peripheral biomarkers are needed to identify the true tumor recurrence and evaluate therapy response. Exosomes isolated from both blood and cerebrospinal fluid are cargo containers utilized by eukaryotic cells to exchange biomolecules such as proteins, mRNA, and microRNA (miRNA). These biomolecules participate in cell-cell communication, cell migration, angiogenesis, and tumor growth. Isolation of RNA (including miRNA) from exosomes can yield a greater concentration compared with circulating mRNA directly taken from body fluid as molecules within exosomes are not degraded by nucleases and proteases. Not only are exosomes a novel approach to biomarker detection, but they may also provide potential therapeutic interventional targets. In addition, exosomes are critical in miRNA replacement therapy as they can act as a carrier for anticancer drug delivery. This review focuses on the advances in basic research of exosome-related potential biomarkers and discusses their potential application in the diagnosis, prognosis, and treatment of GBM.

Impact of Resecting Radiation Necrosis and Pseudoprogression on Survival of Patients with Glioblastoma

Radiation necrosis (RN) and pseudoprogression are known as postradiation treatment effects and may simulate tumor progression. The disease course of glioblastoma patients who had developed RN and the impact of resecting RN on survival have not been evaluated. This study examines the clinical course of patients considered candidates for repeat surgery for a recurring brain mass proven to be RN and compared these with patients who had true tumor recurrence at surgery. Of 159 patients with glioblastoma who were reoperated on because of a presumed recurrent tumor requiring repeat surgery, 18 had RN as the major component of the resected mass. The characteristics and outcome of these 18 patients were retrospectively analyzed and compared with patients in whom active and bulky tumor was found during surgery. Radiation necrosis occurred significantly earlier than true tumor recurrence. Patients with RN harbored larger lesions and were significantly more symptomatic before the second surgery. Most patients with RN who underwent GTR of the lesion in the second operation experienced faster resolution of the surrounding edema compared with patients who underwent STR or biopsy only. There was no significant difference in survival between the 2 groups. These data provide an opportunity to examine the clinical course of a selected group of patients with histologically verified RN. Although RN is associated with more severe neurologic symptoms that improve after surgery, its occurrence or surgical removal carries no survival advantage compared with patients who undergo a repeat operation for true tumor recurrence.

Histopathological correlates with survival in reoperated glioblastomas

The addition of concomitant and adjuvant chemotherapy to radiation therapy after surgical resection has increased significantly the survival of patients with glioblastoma (GB). In conjunction, there has been an increasing fraction of patients who present with new enlarged areas of contrast enhancement and edema on post-treatment imaging that improve without further treatment. It remains to be established how this phenomenon, commonly termed pseudoprogression, can be distinguished from true tumor recurrence defined as the histological presence of active high-grade tumor, as well as its prognostic significance. Data for over 500 patients undergoing surgery for recurrent GB were reviewed. Pathological specimens were categorized as those that contained active high-grade glioma in any amount, and those that did not. Patient survival was compared between these two groups, and independent associations were assessed using Cox proportionate hazards regression analysis. 59 patients met the study criteria including complete pathological and follow-up data. Mean age was 53 ± 11 years. Median survival from suspected recurrence and initial diagnosis were 8 [5-14] and 20 [12-30] months. Seventeen patients (29 %) had no evidence of active high-grade tumor and 42 (71 %) had at least focal active high-grade glioma. Pathologic pseudoprogression at re-operation (p = 0.03) and gross total resection (p = 0.01) were independently associated with survival. The histopathological features defined here and used to assess the tumor at reoperation were independently associated with survival. These findings may be important in designing treatment strategies and clinical trial endpoints for patients with GB.

99mTc-Tetrofosmin SPECT for the detection of glioma recurrence

Dear Sir, We read with great interest the article by Gomez-Rio et al. concerning the distinction between tumor recurrence and radiation necrosis using thallium-201 (Tl) singlephoton emission computed tomography (SPECT) and 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) [1]. The authors studied 76 brain tumor patients suspicious of glioma recurrence after surgical excision and radiotherapy. The results showed that although FDG-PET yielded a slight higher specificity, the sensitivity was considerably lower. Thus, Tl-SPECT was superior in detecting radiation necrosis, especially in low-grade tumors. Radiation necrosis is one of the most serious complications of radiation therapy for the brain and is usually indistinguishable from true tumor recurrence by means of computed tomography and magnetic resonance imaging (MRI) alone. Furthermore, an accurate diagnosis is crucial for the patient’s management because therapy and prognosis are so distinctly different for these lesions. Several advanced MRI techniques, that provide significantly more information about tissue characterization, have been evaluated toward distinguishing radiation necrosis from tumor recurrence, such as diffusionand perfusion-weighted imaging and magnetic resonance spectroscopic evaluation. Functional metabolic imaging by PET and SPECT has also been evaluated; nonetheless, PET is often cost-prohibitive and not widely available. Brain SPECT has been proposed as an alternative imaging technique. Tl was among the first tracers evaluated, while technetium-99m (Tc)-labeled compounds have also been studied and proved advantageous over Tl due to the 140-keV γ-ray energy and higher photon flux, resulting in improved spatial resolution with significantly lower radiation burden to the patient [2]. Among Tc-labeled compounds, Tc-Sestamibi has been proven a suitable radiotracer [2, 3]. Over the last few years, we have investigated the imaging properties of Tc-Tetrofosmin (Tc-TF), a tumor-seeking lipophilic diphosphine routinely used for myocardial perfusion imaging [3]. Tc-TF does not cross the intact blood–brain barrier and its uptake depends on regional blood flow and cell membrane integrity, thus reflecting on cellular metabolic status and viability. We fount that Tc-TF could reliably distinguish between tumor recurrence and radiation injury [4]. We also evaluated the relationship between glioma and meningioma proliferation (as expressed by the Ki-67 index and flow cytometry) and the uptake of Tc-TF. In both tumor types, we verified a strong positive linear correlation between tracer uptake and tumor aggressiveness [5–7]. Soricelli et al. have also reported, in a study of 26 brain tumor patients, that Tc-TF was superior to Tl in depicting tumor margins, exhibiting higher lesion-to-background ratio [8]. Eur J Nucl Med Mol Imaging (2008) 35:1571–1572 DOI 10.1007/s00259-008-0824-z

New Primary Basal Cell Carcinomas Arising in Skin Flaps Following Mohs Micrographic Surgery for Primary and Recurrent Basal Cell Carcinoma

Two patients developed new primary basal cell carcinomas (BCCs) in skin flaps used to reconstruct wounds that followed an earlier primary BCC and a recurrent BCC treated by Mohs micrographic surgery. Criteria for distinguishing a new primary BCC arising in a skin flap or full-thickness skin graft at a previous treatment site for BCC from a truly recurrent BCC are presented. The distinction between a new primary BCC and true tumor recurrence is important for accurate clinical assessment and may have a dramatic impact on the type of subsequent treatment. In addition, there may be less medicolegal liability in the case of a new primary BCC arising at the site of a previously treated BCC than for a BCC that is determined to be recurrent.

CT-guided percutaneous bowel loopogram.

CT-guided percutaneous bowel loopogramWK Hoddick, BE Demas and AA MossAudio Available | Share