Diagnosis Of Tumor Recurrence Research Articles

The diagnostic accuracy of mammography and ultrasonography for recurrent breast cancer after breast conserving treatment

ObjectiveTo evaluate the performance of mammography and breast ultrasonography to diagnose tumor recurrence in patients after breast conserving therapy. Material and MethodsImaging findings of 130 breast cancer patients treated by breast conserving therapy (BCT) who have followed up with mammography and ultrasonography at our center between 1 st January 2010 and 1st January 2016 were interpreted by two radiologists. The information of recurrent tumor and baseline data were blinded. Imaging interpretation followed the ACR Breast imaging-reporting and data system (BI-RADS) 5th edition guideline. Findings of mammography, breast ultrasonography, demographic data and histological data were recorded and analyzed. ResultsThe presence of mass in mammography (P-value=0.025) and internal vascularity in mass in ultrasonography (P-value<0.001) were associated with recurrent tumor at the surgical bed. All the recurrent tumors were interpreted as BI-RADS 4 (71 patients) with sensitivity= 100%, specificity= 89.5%. BIRADS4 is significant in the diagnosis of recurrent breast cancer in BCT patients (AUC of the ROC curve = 0.742 and 95% CI=(0.7–0.79)). ConclusionThe presence of mass in mammography and internal vascularity in the mass in ultrasonography are the imaging findings which were significantly related to recurrent tumor at surgical bed in patient with breast conserving treatment.

The complementary role of MRI and FET PET in high-grade gliomas to differentiate recurrence from radionecrosis.

Conventional magnetic resonance imaging (MRI) has limitations in differentiating tumor recurrence (TR) from radionecrosis (RN) in high-grade gliomas (HGG), which can present with morphologically similar appearances. Multiparametric advanced MR sequences and Positron Emission Tomography (PET) with amino acid tracers can aid in diagnosing tumor metabolism. The role of both modalities on an individual basis and combined performances were investigated in the current study. Patients with HGG with MRI and PET within three weeks were included in the retrospective analysis. The multiparametric MRI included T1-contrast, T2-weighted sequences, perfusion, diffusion, and spectroscopy. MRI was interpreted by a neuroradiologist without using information from PET imaging. 18F-Fluoroethyl-Tyrosine (FET) uptake was calculated from the areas of maximum enhancement/suspicion, which was assessed by a nuclear medicine physician (having access to MRI to determine tumor-to-white matter ratio over a specific region). A definitive diagnosis of TR or RN was made based on the combination of multidisciplinary joint clinic decisions, histopathological examination, and clinic-radiological follow-up as applicable. 62 patients were included in the study between July 2018 and August 2021. The histology during initial diagnosis was glioblastoma, oligodendroglioma, and astrocytoma in 43, 7, and 6 patients, respectively, while in 6, no definitive histological characterization was available. The median time from radiation (RT) was 23 months. 46 and 16 patients had TR and RN recurrence, respectively. Sensitivity, specificity, and accuracy using MRI were 98, 77, and 94%, respectively. Using PET imaging with T/W cut-off of 2.65, sensitivity, specificity, and accuracy were 79, 84, and 80%, respectively. The best results were obtained using both imaging combined with sensitivity, specificity, and accuracy of 98, 100, and 98%, respectively. Combined imaging with MRI and FET-PET offers multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.

Diagnostic Accuracy of Arterial Spin-Labeling, Dynamic Contrast-Enhanced, and DSC Perfusion Imaging in the Diagnosis of Recurrent High-Grade Gliomas: A Prospective Study.

For patients with high-grade gliomas, the appearance of a new, enhancing lesion after surgery and chemoradiation represents a diagnostic dilemma. We hypothesized that MR perfusion without and with contrast can differentiate tumor recurrence from radiation necrosis. In this prospective study, we performed 3 MR perfusion methods: arterial spin-labeling, DSC, and dynamic contrast enhancement. For each lesion, we measured CBF from arterial spin-labeling, uncorrected relative CBV, and leakage-corrected relative CBV from DSC imaging. The volume transfer constant and plasma volume were obtained from dynamic contrast-enhanced imaging without and with T1 mapping using modified Look-Locker inversion recovery (MOLLI). The diagnosis of tumor recurrence or radiation necrosis was determined by either histopathology for patients who underwent re-resection or radiologic follow-up for patients who did not have re-resection. There were 26 patients with 32 lesions, 19 lesions with tumor recurrence and 13 lesions with radiation necrosis. Compared with radiation necrosis, lesions with tumor recurrence had higher CBF (P = .033), leakage-corrected relative CBV (P = .048), and plasma volume using MOLLI T1 mapping (P = .012). For differentiating tumor recurrence from radiation necrosis, the areas under the curve were 0.81 for CBF, 0.80 for plasma volume using MOLLI T1 mapping, and 0.71 for leakage-corrected relative CBV. A correlation was found between CBF and leakage-corrected relative CBV (r s = 0.54), volume transfer constant, and plasma volume (0.50 < r s< 0.77) but not with uncorrected relative CBV (r s = 0.20, P = .29). In the differentiation of tumor recurrence from radiation necrosis in a newly enhancing lesion, the diagnostic value of arterial spin-labeling-derived CBF is similar to that of DSC and dynamic contrast-enhancement-derived blood volume.

Management of Contralateral Breast and Axillary Nodes Silicone Migration after Implant Rupture.

Background:Silicone implants were developed in 1962 for breast augmentation and became essential in reconstruction after mastectomy. Silicone “bleeding” has been described from both ruptured and intact implants and can induce disseminated granulomatosis due to the component's high fat solubility. If not adequately treated, they can lead to disastrous cosmetic and functional consequences. Because they may mimic malignancy, prompt and reliable diagnosis should be made as early as possible.Methods:We present a clinical case description of multiple intraparenchymal and ipsi/contralateral intraganglionic siliconomas in a woman who had undergone breast reconstruction, and a literature review of the pathophysiology of siliconomas and their diagnosis and management.Results:Silicone migration to the contralateral breast and lymph node is rare and has seldom been described. The mechanism is still debated. Excluding malignancy is a priority, and systematic management must be respected to avoid misdiagnosis or unnecessary investigations.Conclusions:A multidisciplinary approach is essential for siliconoma management. Silicone-related lymphadenopathies do not require follow-up or special treatment unless they interfere with the diagnosis of tumor recurrence. Careful observation is sufficient for asymptomatic siliconomas; however, symptomatic ones should be treated depending on skin involvement and the patient's eligibility for intervention.

Identify glioma recurrence and treatment effects with triple-tracer PET/CT

BackgroundDifferential diagnosis of tumour recurrence (TuR) from treatment effects (TrE), mostly induced by radiotherapy and chemotherapy, is still difficult by using conventional computed tomography (CT) or magnetic resonance (MR) imaging. We have investigated the diagnostic performance of PET/CT with 3 tracers, 13N-NH3, 18F-FDOPA, and 18F-FDG, to identify TuR and TrE in glioma patients following treatment.MethodsForty-three patients with MR-suspected recurrent glioma were included. The maximum and mean standardized uptake values (SUVmax and SUVmean) of the lesion and the lesion-to-normal grey-matter cortex uptake (L/G) ratio were obtained from each tracer PET/CT. TuR or TrE was determined by histopathology or clinical MR follow-up for at least 6 months.ResultsIn this cohort, 34 patients were confirmed to have TuR, and 9 patients met the diagnostic standard of TrE. The SUVmax and SUVmean of 13N-NH3 and 18F-FDOPA PET/CT at TuR lesions were significantly higher compared with normal brain tissue (13N-NH3 0.696 ± 0.558, 0.625 ± 0.507 vs 0.486 ± 0.413; 18F-FDOPA 0.455 ± 0.518, 0.415 ± 0.477 vs 0.194 ± 0.203; both P < 0.01), but there was no significant difference in 18F-FDG (6.918 ± 3.190, 6.016 ± 2.807 vs 6.356 ± 3.104, P = 0.290 and 0.493). L/G ratios of 13N-NH3 and 18F-FDOPA were significantly higher in TuR than in TrE group (13N-NH3, 1.573 ± 0.099 vs 1.025 ± 0.128, P = 0.008; 18F-FDOPA, 2.729 ± 0.131 vs 1.514 ± 0.141, P < 0.001). The sensitivity, specificity and AUC (area under the curve) by ROC (receiver operating characteristic) analysis were 57.7%, 100% and 0.803, for 13N-NH3; 84.6%, 100% and 0.938, for 18F-FDOPA; and 80.8%, 100%, and 0.952, for the combination, respectively.ConclusionOur results suggest that although multiple tracer PET/CT may improve differential diagnosis efficacy, for glioma TuR from TrE, 18F-FDOPA PET-CT is the most reliable. The combination of 18F-FDOPA and 13N-NH3 does not increase the diagnostic efficiency, while 18F-FDG is not worthy for differential diagnosis of glioma TuR and TrE.

Late recurrences of pancreatic cancer in patients with long-term survival after pancreaticoduodenectomy.

Pancreatic cancer remains a relevant clinical problem due to poor prognosis. Even after curative pancreaticoduodenectomy tumor recurrences occur in up to 80%. Risk factors for postoperative tumor recurrences have been identified before, but data on risk factors for tumor recurrences in patients with long-term-survival is scarce. In this retrospective study consecutive long-term survival-patients (defined as at least 60 months survival) undergoing pancreaticoduodenectomy for pancreatic cancer from 2007-2014 were identified in the 2nd largest pancreatic surgery center in Germany. Clinical, pathohistological and laboratory values were analyzed to identify risk factors for tumor recurrence. Thirty-four of one-hundred-sixty-seven patients were identified as long-term-survival-patients in the study period. Of those, 10 patients (29.4%) suffered from tumor recurrence. Lymph vessel invasion was identified as an independent risk factor (P=0.031, hazard ratio 13.127, 95% confidence interval: 1.270-135.698). Median postoperative time to tumor recurrence in long-term-survival-patients was 49 months. Overall survival after diagnosis of tumor recurrence was 33 months. 80% (N=8) of the patients were asymptomatic. Half of the patients (N=5) suffered from local disease, with 40% undergoing curative tumor resection. CA 19-9 levels were significantly elevated at 57 U/mL (normal <27 U/mL). Tumor recurrence in long-term-survival-patients is typically asymptomatic. Especially long-term-survival-patients with lymph vessel invasion are more likely to develop tumor recurrence. Therefore, a structured follow-up program including CT-scans and CA 19-9 surveillance must be continued in all patients undergoing pancreaticoduodenectomy even in cases of long-term-survival.

A systematic review of the utility of amino acid PET in assessing treatment response to bevacizumab in recurrent high-grade glioma.

Background. Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas (rHGG). BEV has shown to decrease enhancement on MRI, but it is often unclear if these changes are due to tumor response to BEV or treatment-induced changes in the blood brain barrier. Preliminary studies show that amino acid PET can aid in distinguishing these changes on MRI.Methods. The authors performed a systematic review of PubMed and Embase through July 2020 with the search terms ‘bevacizumab’ or ‘Avastin’ and ‘recurrent glioma’ and ‘PET,’ yielding 38 papers, with 14 meeting inclusion criteria. Results. Thirteen out of fourteen studies included in this review used static PET and three studies used dynamic PET to evaluate the use of BEV in rHGG. Six studies used the amino acid tracer [18F]FET, four studies used [11C]MET, and four studies used [18F]FDOPA. Conclusion. [18F]FET, [11C]MET, and [18F]FDOPA PET in combination with MRI have shown promising results for improving accuracy in diagnosing tumor recurrence, detecting early treatment failure, and distinguishing between tumor progression and treatment-induced changes in patients with rHGG treated with BEV.

The role of extracellular vesicles in the diagnosis of glioblastoma progression

The article reviews studies highlighting the role of extracellular molecules in non-invasive diagnosis of glioblastoma recurrence. Glioblastoma is the most common malignant tumor of the brain characterized by fatal outcome prognosis. Current treatment of tumor recurrence allows to increase patient survival, improve functional outcome and decrease caregivers» load. The standard method of recurrence diagnosis is neuroimaging which at early stages cannot distinguish between tumor recurrence and post-radiation changes. Currently in oncology, liquid biopsy and marker detection in circulating extracellular vesicles are considered promising approaches allowing to obtain early and differential tumor diagnosis, determine dynamic molecular and genetic status of the tumor, diagnose tumor recurrence at early stages. In this context, the most promising approach to glioblastoma diagnosis is associated with studying of expression of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), its mutant variant EGFRvIII, podoplanin (PDPN) and isocitrate dehydrogenase 1 (IDH1) in extracellular vesicles; for primary glioblastoma diagnosis and early recurrence: studying of microRNA-210, -301a, -222, -123-3p, -21; for control of immunotherapy effectiveness in patients with recurrent forms of glioblastoma after standard treatment: evaluation of СD9+ / GFAP+ / survivin+ exosomes in plasma.

Effect of postoperative apatinib treatment after resection of hepatocellular carcinoma with portal vein invasion: A phase II study.

514 Background: Adjuvant therapy for hepatocellular carcinoma (HCC) is an unmet need. Apatinib, a VEGFR2 inhibitor, showed antitumor activity and tolerable toxicity for advanced HCC in a phase 2 study. We were aiming to explore the safety and efficacy of apatinib in adjuvant settings after resection of HCC with portal vein tumor thrombosis (PVTT). Methods: This is a single-center single-arm phase 2 study. The key inclusion criteria were: (1) pathologically confirmed HCC; (2) underwent liver resection with curative intention within 4-6 wk before recruitment; (3) PVTT assessed by preoperative imaging or intraoperative findings. Eligible pts received apatinib at 500 mg/day for a maximum of 12 mo until unacceptable toxicity or tumor recurrence. The primary outcome was recurrence-free survival (RFS) defined as the interval between surgery and the diagnosis of tumor recurrence or death from any causes whichever comes first. The secondary outcome is overall survival (OS) and treatment safety. Results: From Aug 17, 2017 to Dec 18, 2018, 49 pts were screened, and 30 pts were recruited. PVTT were classified as Vp1 (n = 7), Vp2 (n = 11), and Vp3 (n = 12) according to the LCSGJ classification. As the data cutoff on Aug 22, 2019, 4 pts are still on treatment. The median follow-up was 14.3 mo (IQR 12.3-19.3). Median duration of treatment was 4.8 mo (IQR 2.0–8.8). 20 recurrence and 2 death occurred including one death without recurrence. The mRFS was 7.6 mo (95% CI, 3.7-11.5), and the 1-year RFS rate was 36.1%. The mOS was not reached, and 1-year OS rate was 93.3% (standard error, 4.6%). Treatment-related adverse events occurred in 29 pts (96.7%). Grade 3 or 4 adverse events were reported in 14 pts (46.7%) (Table). Dose modification due to adverse events was recorded in 23 pts (76.7%). Conclusions: Apatinib is tolerant in most pts after resection for HCC with PVTT. A controlled study is warranted to prove its efficacy on tumor recurrence. Clinical trial information: NCT03261791. [Table: see text]

Individualized discrimination of tumor recurrence from radiation necrosis in glioma patients using an integrated radiomics-based model

PurposeTo develop and validate an integrated model for discriminating tumor recurrence from radiation necrosis in glioma patients.MethodsData from 160 pathologically confirmed glioma patients were analyzed. The diagnostic model was developed in a primary cohort (n = 112). Textural features were extracted from postoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), 11C-methionine (11C-MET) PET, and magnetic resonance images. The least absolute shrinkage and selection operator regression model was used for feature selection and radiomics signature building. Multivariable logistic regression analysis was used to develop a model for predicting tumor recurrence. The radiomics signature, quantitative PET parameters, and clinical risk factors were incorporated in the model. The clinical value of the model was then assessed in an independent validation cohort using the remaining 48 glioma patients.ResultsThe integrated model consisting of 15 selected features was significantly associated with postoperative tumor recurrence (p < 0.001 for both primary and validation cohorts). Predictors contained in the individualized diagnosis model included the radiomics signature, the mean of tumor-background ratio (TBR) of 18F-FDG, maximum of TBR of 11C-MET PET, and patient age. The integrated model demonstrated good discrimination, with an area under the curve (AUC) of 0.988, with a 95% confidence interval (CI) of 0.975–1.000. Application in the validation cohort showed good differentiation (AUC of 0.914 and 95% CI of 0.881–0.945). Decision curve analysis showed that the integrated diagnosis model was clinically useful.ConclusionsOur developed model could be used to assist the postoperative individualized diagnosis of tumor recurrence in patients with gliomas.

Diagnostic impact of additional O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET following immunotherapy with dendritic cell vaccination in glioblastoma patients

Objective Vaccination therapy using tumour antigen-loaded, autologous dendritic cells (DC) is a promising therapeutic approach alongside standard treatment for glioblastoma (GBM). However, reliable diagnostic criteria regarding therapy monitoring are not established. Here, we analysed the impact of additional 18F-fluoroethyl-tyrosine positron emission tomography (18F-FET PET) imaging following DC vaccination therapy. Methods We analysed data of GBM patients who received DC vaccination therapy. Following MRI diagnosis of tumour recurrence, additional static and dynamic 18F-FET PET imaging was performed. Vaccination was performed five times by intradermal injections, either weekly between concomitant radio/-chemotherapy and intermittent chemotherapy or after tumour recurrence, before re-radiation therapy. MRI and 18F-FET PET results were compared and correlated with clinical data. Results Between 2003 and 2016, 5 patients were identified who received DC vaccination and 18F-FET PET imaging (1 female/4 males; mean age: 44 ± 14 y). 3/5 patients showed congruent results of tumour progression. In three patients 18F-FET PET indicated treatment related changes, which was in contrast to MRI findings that indicated tumour progression. In these patients 18F-FET PET results could be confirmed by either neuropathological diagnosis or according to the RANO criteria Conclusions Despite the small patients number our results indicate an additional impact of 18F-FET PET for monitoring outcome following vaccination therapy.

RADI-43. ARTERIAL SPIN LABELING PERFUSION MR IMAGING FOR DIFFERENTIATION BETWEEN TUMOR RECURRENCE AND PSEUDOPROGRESSION IN INTRACRANIAL METASTASES FOLLOWING STEREOTACTIC RADIOSURGERY

Stereotactic radiosurgery (SRS) is a standard adjuvant treatment for patients with limited intracranial metastatic disease. Transient growth, increased peritumoral edema, and inflammation can be seen in up to a third of these cases following SRS. Unfortunately, this pseudoprogression is often indistinguishable from true progression by morphologic MR imaging thereby complicating patient management. The purpose of this study was to evaluate whether arterial spin labeling (ASL) perfusion can differentiate tumor recurrence from pseudoprogression after SRS. We reviewed patients treated between 2013 and 2018 and identified 24 patients with 43 intracranial metastases who had imaging suggesting progression following SRS and also had ASL perfusion acquired at time of MR imaging. Median imaging follow-up was 11 months (range 3–64 months). Outcome of tumor recurrence or pseudoprogression was confirmed in each case by pathology or subsequent MR imaging. 25 (58%) lesions were classified as tumor recurrence (13, 52% by pathology), while 18 (42%) were classified as pseudoprogression (3, 18% by pathology). ASL perfusion values (normalized cerebral blood flow) were higher in patients with tumor progression (2.1 vs 1.1 ml/min/100g, p=0.003). No significant difference was observed between histology, time from radiotherapy, marginal dose, volume of lesion, or instances of repeat SRS treatments between groups. In conclusion, elevated blood flow by ASL perfusion was closely associated with the diagnosis of tumor recurrence after SRS. Patients with intracranial metastases undergoing SRS may benefit from this short non-contrast sequence at time of follow-up MR imaging.

DCE and DSC perfusion MRI diagnostic accuracy in the follow-up of primary and metastatic intra-axial brain tumors treated by radiosurgery with cyberknife

BackgroundThe differential diagnosis between radiation necrosis, tumor recurrence and tumor progression is crucial for the evaluation of treatment response and treatment planning.The appearance of treatment-induced tissue necrosis on conventional Magnetic Resonance Imaging (MRI) is similar to brain tumor recurrence and it could be difficult to differentiate the two entities on follow-up MRI examinations.Dynamic Susceptibility Contrast-enhanced (DSC) and Dynamic Contrast-Enhanced (DCE) are MRI perfusion techniques that use an exogenous, intravascular, non-diffusible gadolinium-based contrast agent.The aim of this study was to compare the diagnostic accuracy of DSC and DCE perfusion MRI in the differential diagnosis between radiation necrosis and tumor recurrence, in the follow-up of primary and metastatic intra-axial brain tumors after Stereotactic RadioSurgery (SRS) performed with CyberKnife.MethodsA total of 72 enhancing lesions (57 brain metastases and 15 primary brain tumors) were analyzed with DCE and DSC, by means of MRI acquisition performed by 1,5 Tesla MR scanner. The statistical relationship between the diagnosis of tumor recurrence or radiation necrosis, decided according to clinicoradiologically criteria, rCBV and Ktrans was evaluated by the point-biserial correlation coefficient respectively.ResultsThe statistical analysis showed a correlation between the diagnosis of radiation necrosis or recurrent tumor with Ktrans (rpb = 0.54, p < 0.001) and with rCBV (rpb = 0.37, p = 0.002).The ROC analysis of rCBV values demonstrated a good classification ability in differentiating radiation necrosis from tumour recurrence as well as the Ktrans. The optimal cut-off value for rCBV was k = 1.23 with 0.88 of sensitivity and 0.75 of specificity while for Ktrans was k = 28.76 with 0.89 of sensitivity and 0.97 of specificity.ConclusionsMRI perfusion techniques, particularly DCE, help in the differential diagnosis by tumor recurrence and radiation necrosis during the follow-up after radiosurgery.

Analysis of clinical features and prognostic factors on reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor

To investigate the clinical characteristics and prognostic factors of reoperation patients with postoperative recurrence or metastasis of gastrointestinal stromal tumor (GIST). A retrospective case-control study was performed on the clinical data of 31 patients with GIST who had recurrence or metastasis after the first surgery and underwent one or more operations again from February 2003 to January 2016 at Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The clinical characteristics of these patients were analyzed. Kaplan-Meier survival curve was used to calculate the survival rate, Cox univariate and multivariate regression model was applied to prognosis analysis. Age of these 31 patients at the first operation was 35-78 (median 49) years, including 17 males (54.8%) and 14 females (45.2%). The tumors of 21 cases located in small intestines (67.7%), 2 cases in stomach (6.5%), 4 cases (12.9%) in colorectum and of 4 cases (12.9%) in other sites. According to NIH criteria, risk assessment indicated 26 cases were(83.8%) with high risk, 3 cases (9.7%) with moderate risk, and 2 cases (6.5%) with low risk. After the first operation, 15 cases received the IM (imatinib) therapy regularly based on NCCN guideline,10 cases received the therapy irregularly, and the other 6 cases did not receive the therapy. R0 resection was performed in 29 cases (93.5%) and R1/R2 resection was performed in 2 cases (6.5%). The median interval between the first operation to the recurrence was 32.3 (5.2-117.6) months and the median age of recurrence was 56 years old. Refer to the recurrent location, 28 cases (90.3%) were found in the same location or liver, 1 case in greater omentum, and 2 cases in pelvic cavity. The median diameter of the tumor in reoperation was 6.5 cm. Twenty-three cases(74.2%) received R0 excision and the other 8 cases(25.8%) received R1/R2 excision. At diagnosis of tumor recurrence, 20 cases (64.5%) received the second surgery immediately and the other 11 cases received surgery after imatinib or sunitinib treatment. Twenty-nine (93.5%) patients were followed up for 7.3 to 160.3 (median 49.5) months. After the second surgery, the relapse-free survival (RFS) of the whole group was 3.2 to 148.6(median: 29.7) months. Till the end of follow-up, 9 cases died of recurrence. Among 20 alive cases, 8 cases were living with the tumor, 1 case received the third surgery. The median overall survival (OS) time was 38.4(6.2-160.3) months. The 5-year RFS and the 5-year OS of 15 cases who received regular targeted therapy after the first operation were 73.4% and 81.7% respectively, significantly higher than those of the other 16 cases who received irregular or no targeted therapy(37.6%, P=0.015 and 38.9%,P=0.023,respectively). The 5-year RFS rate and the 5-year OS rate of the 11 patients who were diagnosed or complicated with liver metastasis were 29.8% and 32.2% respectively, which were significantly lower than those of the 20 patients without liver metastasis (79.1% and 88.1% respectively, both P<0.001). Cox model for OS, the results showed that regular targeted therapy after first surgery(HR=0.362, 95%CI:0.210-1.074, P=0.089) and the liver metastasis (HR=5.342, 95%CI: 0.902-12.580, P=0.057) were not the independent risk factors. Regular targeted therapy according to the guideline after the first operation for GIST patients with recurrence or metastasis may improve the prognosis. Prognosis of GIST patients with postoperative liver metastasis is poor.

Imaging of Posttreatment Salivary Gland Tumors.

The aim of this study is to review the imaging appearance of posttreatment salivary gland tumors. The authors discuss the imaging appearance of parotidectomy and reconstructive surgery of parotid defects. Imaging is important to diagnose tumor recurrence and also assess for complications related to surgery, such as a sialocele, fluid collection, hematoma, pseudoaneurysm, and graft stenosis. The article also provides a current-state assessment of the applications of advanced imaging techniques.

EBUS-TBNA in PET-positive lymphadenopathies in treated cancer patients.

Mediastinal lymph node enlargement is common in the follow-up of patients with previously treated malignancies. The aim of this study is to assess the role of endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) for cyto-histological evaluation of positron emission tomography with 18fluorodeoxyglucose (PET) positive mediastinal and hilar lymph nodes developed in patients with previous malignancies.All EBUS-TBNA cases performed from January 2012 to May 2016 were retrospective reviewed. Results of EBUS-TBNA in patients with mediastinal and/or hilar lymphadenopathies were analysed. Non-malignant cytopathologies were confirmed with surgical procedures or clinical and radiological follow-up.Among 1780 patients, 176 were included in the analysis. 103 of these (58.5%) had a diagnosis of tumour recurrence whereas 73 (41.5%) had a different diagnosis: 63 (35.8%) had a non-neoplastic diagnosis and 8 patients (4.6%) had a different cell type malignancy. Samples were false-negative in 5 (2.8%) out of 176 patients. The overall sensitivity, specificity, negative predicted value and diagnostic accuracy were 95.7% (95% CI 90.2–98.6%), 100% (95% CI 94.0–100%), 92.3% (95% CI 83.2–96.7%) and 97.2% (95% CI 93.5–98.8%), respectively.EBUS-TBNA demonstrated a pathological diagnosis different from the previous tumour in a large percentage of patients, confirming its strategic role in the management of patients with previously treated malignancies.

The Development of Reduced Diffusion Following Bevacizumab Therapy Identifies Regions of Recurrent Disease in Patients with High-grade Glioma

The treatment of glioma with bevacizumab results in decreased enhancement, making it challenging to diagnose tumor recurrence. Therefore, the primary aim of this retrospective study was to determine if the underlying biological processes occurring within regions of recurrent glioblastoma in patients undergoing bevacizumab therapy influence morphologic and diffusion-weighted magnetic resonance (MR) imaging characteristics. In this Health Insurance Portability and Accountability Act-compliant and institutional review board-approved study, 26 patients treated with bevacizumab for high-grade glioma underwent lesion-wide apparent diffusion coefficient analysis before therapy and at the time of clinical/radiological progression, allowing for stratification by the presence or absence of reduced diffusion. Lesions with reduced diffusion were classified into "block" or "salt & pepper" phenotypes. Eight of the 26 patients underwent image-guided tissue sampling at the time of suspected disease recurrence allowing for direct biological correlation. Clinical, histologic, and MR imaging differences between diffusion groups were assessed using a two-sample Welch t test. All patients had histologic evidence of recurrent disease with or without a background of treatment effect. Sixty-two percent of the cohort had developed reduced diffusion at clinical progression following bevacizumab. Image-guided tissue sampling demonstrated that treatment effect was not observed within regions of reduced diffusion. Recurrent tumor intermixed with treatment effect was more likely to be observed within the "salt & pepper" phenotype when compared to "block" phenotype. Following bevacizumab therapy, recurrent glioblastoma can manifest as nonenhancing regions characterized by reduced diffusion. Histologically, these MR imaging characteristics correlate with aggressive biological features of disease recurrence.

Prognostic Value of O-(2-[18F]-Fluoroethyl)-L-Tyrosine-Positron Emission Tomography Imaging for Histopathologic Characteristics and Progression-Free Survival in Patients with Low-Grade Glioma

O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography ((18)F-FET-PET) imaging is applied for tumor grading, prognostic stratification, and diagnosis of tumor recurrence, especially in high-grade gliomas. Experience with (18)F-FET-PET imaging in low-grade gliomas is limited. Therefore, the objective of the present study was to assess (18)F-FET-PET tracer uptake in low-grade gliomas and to investigate possible correlations with contrast enhancement in magnetic resonance imaging (MRI) and histopathology. A total of 65 patients (29 female, 36 male, median age 38 years) with newly diagnosed or recurrent low-grade gliomas for whom preoperative MRI and (18)F-FET-PET imaging were available were included. Tumor entity, tumor location, as well as histopathology (isocitrate dehydrogenase [IDH] 1/2 mutation, Ki67, p53, oligodendroglial differentiation, 1p19q codeletion), and progression-free survival were assessed. (18)F-FET-PET images were acquired and fused to MRI (T2-weighted fluid-attenuated inversion recovery) and tumor volume was measured in areas with a tumor-to-background ratio >1.3, >1.6, and >2.0 and in MRI. PET tracer uptake was observed in 78.5% of all World Health Organization Grade I and II tumors. (18)F-FET uptake showed a high negative predictive value for oligodendroglial components and for 1p19q codeletion. No further significant correlation between histologic features, progression-free survival, or IDH1/2 mutation status and tracer uptake was observed. We found that 78.5% of low-grade gliomas do show elevated tracer uptake in (18)F-FET-PET imaging. Low-grade glioma without tracer uptake exclude oligodendroglial differentiation and 1p19q codeletion. Further differentiation between molecular subtypes is not possible with static (18)F-FET-PET. No correlation of progression-free survival to tracer uptake and IDH1/2-mutation status was observed.

Abstract A60: DNA copy-number alterations in primary ovarian serous cystadenocarcinoma encoding for cell transformation and predicting survival and response to platinum therapy throughout the course of the disease.

Abstract Purpose: To examine patterns of primary ovarian serous cystadenocarcinoma (OV) copy-number alterations (CNAs), each of which is correlated with a patient's overall survival (OS) and response to platinum-based chemotherapy at the time of initial diagnosis, over the course of the disease, i.e., in the subpopulations of patients of increasing progression-free survival (PFS) time intervals, from the end of the initial therapy targeting the primary tumor to a diagnosis of tumor recurrence or progression. The patterns of DNA CNAs, across the chromosome arms 7p and, separately, Xq, and across the combination of the two chromosome arms 6p+12p (together but not separately) were recently discovered by using DNA copy-number, i.e., genomic profiles of 249 primary OV tumors, mostly high-grade, from the Cancer Genome Atlas (TCGA) [Sankaranarayanan, Schomay, Aiello and Alter, PLoS One 10 (4), article e0121396 (2015); doi: 10.1371/journal.pone.0121396]. Segmentation of the patterns of DNA CNAs, gene ontology enrichment analyses of the corresponding differential mRNA expression, and mapping of the corresponding differential microRNA and protein expression to the DNA CNAs, linked each pattern with one of three hallmarks of cancer: DNA instability in 7p, cellular immune response suppression in Xq, and a cell's transformation and immortality in 6p+12p (where loss of the p21-encoding CDKN1A and the p38-encoding MAPK14 and gain of KRAS, together but not separately, can lead to transformation of human normal to tumor cells). Survival analyses showed and computationally validated that a combination of the three patterns makes a better predictor of OV survival than the tumor's stage, in the general as well as in the high-grade OV patient population. For &amp;gt;30 years prior, the best predictor of OV survival at the time of initial diagnosis was the tumor's stage. About 25% of primary OV tumors are resistant to platinum therapy, the first-line treatment, yet no diagnostic existed to distinguish resistant from sensitive tumors before the treatment. Methods and Results: By using survival analyses, we find and computationally validate that in the general as well as in the high-grade OV patient population, the three patterns of DNA CNAs are each statistically significantly (log-rank test P-value&amp;lt;0.05) correlated with survival and response to platinum throughout the course of the disease, independent of the primary tumor's stage and other indicators that are determined during treatment, i.e., the residual disease after surgery, the outcome of subsequent therapy, and the neoplasm status, as well as the PFS interval to tumor recurrence or progression. For example, the Kaplan-Meier (KM) median survival times of the 89 high-grade and high-stage patients in the validation set of 148 patients, that were diagnosed with tumor recurrence or progression at any time after the completion of the initial therapy, i.e., PFS&amp;gt;0 months, classified by the combination of the three patterns into three groups A, B, and C, are 72, 55, and 34 months, respectively, such that the median survival time of group A is &amp;gt;3 years greater than, and more than twice that of group C. The KM median survival times of the 56 patients among them with a PFS of &amp;gt;11 months, classified into the same groups, are 72, 58, and 45 months, respectively, such that the median survival time of group A is &amp;gt;2 years greater than that of group C. Conclusion: We find that a primary OV tumor's chromosome arm-wide DNA CNAs, across 7p, Xq, and 6p+12p, can predict a patient's survival and response to platinum beyond the time of initial diagnosis, and throughout the disease, even in patients experiencing complete remission after the treatment of the primary tumor, and independent of the time interval to tumor recurrence or progression. Citation Format: Orly Alter. DNA copy-number alterations in primary ovarian serous cystadenocarcinoma encoding for cell transformation and predicting survival and response to platinum therapy throughout the course of the disease. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A60.

Role of MR Imaging and FDG PET/CT in Selection and Follow-up of Patients Treated with Pelvic Exenteration for Gynecologic Malignancies.

Pelvic exenteration (PE) is a radical surgical procedure used for the past 6 decades to treat locally advanced malignant diseases confined to the pelvis, particularly persistent or recurrent gynecologic cancers in the irradiated pelvis. The traditional surgical technique known as total PE consists of resection of all pelvic viscera followed by reconstruction. Depending on the tumor extent, the procedure can be tailored to remove only anterior or posterior structures, including the bladder (anterior exenteration) or rectum (posterior exenteration). Conversely, more extended pelvic resection can be performed if the pelvic sidewall is invaded by cancer. Preoperative imaging evaluation with magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is central to establishing tumor resectability and therefore patient eligibility for the procedure. These imaging modalities complement each other in diagnosis of tumor recurrence and differentiation of persistent disease from posttreatment changes. MR imaging can accurately demonstrate local tumor extent and show adjacent organ invasion. FDG PET/CT is useful in excluding nodal and distant metastases. In addition, FDG PET/CT metrics may serve as predictive biomarkers for overall and disease-free survival. This pictorial review describes different types of exenterative surgical procedures and illustrates the central role of imaging in accurate patient selection, treatment planning, and postsurgical surveillance.