Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Prediction of extranodal extension in oropharyngeal cancer patients and carcinoma of unknown primary: value of metabolic tumor imaging with hybrid PET compared with MRI and CT.

OBJECTIVES: The aim of this study was to investigate the value of metabolic tumor imaging using hybrid PET for the preoperative detection of extranodal extension (ENE) in lymph node metastases of oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We performed a retrospective analysis of a consecutive cohort of patients with OPSCC treated with primary surgery with or without adjuvant (chemo-) radiotherapy at the Kantonsspital Sankt-Gallen and the University Hospital Zurich, Switzerland, from 2010 until 2019. Hybrid PET was compared to conventional cross-sectional imaging with MRI and CT. Histopathological presence of ENE of neck dissection specimen served as gold standard. RESULTS: A total number of 234 patients were included in the study, 95 (40.6%) of which had pathological ENE (pENE). CT has a good specificity with 93.7%; meanwhile, MRI was the most sensitive diagnostic method (72.0%). The nodal metabolic tumor parameters (SUVmax, TLG, MTV) were significantly higher in patients with positive ENE (p < 0.001 for all three parameters) than in patients with negative ENE (p < 0.001, for all three parameters). CONCLUSIONS: CT achieved the best specificity, while MRI had the best sensitivity to detect ENE. Nodal metabolic tumor parameters differed significantly between ENE-positive/negative and p16-positive/negative patients. Hence, quantitative data obtained by metabolic imaging might predict presence of ENE and, therefore, could be helpful in customizing therapy management.

SUVmax for predicting regional control in oropharyngeal cancer.

PURPOSE: To investigate the predictive value of pretherapeutic metabolic tumor imaging using 18-fluorodeoxyglucose positron emission tomography (FDG-PET) for regional response in oropharyngeal cancer patients undergoing primary (chemo)radiation. METHODS: Retrospective analysis of oropharyngeal cancer patients treated with primary (chemo)radiation at the University Hospital Zurich from 2010 to 2019 with available FDG-PET. The SUVmax of the largest lymph node metastases was recorded. Regional response was assessed using posttherapeutic FDG-PET at 12 weeks and regional recurrence-free survival. RESULTS: 95 patients with a mean age of 68.5 years (SD 10.3) were included. The median pretherapeutic nodal SUVmax was 8.3 (interquartile range 4.4-13.3). A pretherapeutic nodal SUVmax above 6 significantly predicted poorer regional recurrence-free survival (log-rank test, P = 0.009) in univariate analysis. However, in multivariate analysis SUVmax above 6 was not significant in predicting regional recurrence-free survival (Cox regression P = 0.189). Clinical N category showed a trend in which a more severe stage had a poorer regional survival (Cox regression P = 0.073). CONCLUSION: The SUVmax of the largest lymph node metastasis seems to play a role in predicting regional response in oropharyngeal cancer patients, after stratifying for N category. More research is needed to investigate whether highly metabolically active disease is less likely to respond to chemoradiation.

WITHDRAWN: Evaluation of multifunctional imaging parameters in gastro-oesophageal cancer using F-18-FDG-PET/CT with integrated perfusion CT.

Ahead of Print article withdrawn by publisher.

Combined PET/CT-perfusion in patients with head and neck cancers might predict failure after radio-chemotherapy: a proof of concept study.

BACKGROUND: [18F]FDG-PET/CT imaging is broadly used in head and neck cancer (HNSCC) patients. CT perfusion (CTP) is known to provide information about angiogenesis and blood-flow characteristics in tumors. The aim of this study was to evaluate the potential relationship of FDG-parameters and CTP-parameters in HNSCC preand post-therapy and the potential prognostic value of a combined PET/CT with CTP. METHODS: Thirteen patients with histologic proven HNSCC were prospectively included. All patients underwent a combined PET/CT with integrated CTP before and after therapy. Pre- and post-therapeutic data of CTP and PET of the tumors were compared. Differences were tested using Spearman's rho test and Pearson's correlation. A p-value of p <0.05 was considered statistically significant. Correlations were calculated using Pearson's correlation. Bootstrap confidence intervals were calculated to test for additive confidence intervals. RESULTS: Three patients died due to malignancy recurrence, ten patients were free of recurrence until the end of the follow-up period. Patients with recurrent disease had significantly higher initial CTP-values compared to the recurrence-free patients: BFpre 267.4 (171.2)ml/100 mg/min, BVpre 40.9 (8.4)ml/100 mg and MTTpre 8.2 (6.1)sec. No higher SUVs initially but significantly higher TLG compared to patients without recurrence were found. Post-therapeutic PET-values differed significantly between the two groups: SUVmaxpost 6.0 (3.2), SUVmeanpost 3.6 (2.0) and TLG 21751.7 (29794.0). CONCLUSION: In our proof of concept study, combined PET/CT with integrated CTP might show complementary prognostic data pre- and post chemo-radiotherapy. CTP may be used to predict local tumor recurrence, while FDGPET/CT is still needed for whole-body staging.

Protocol requirements and diagnostic value of PET/MR imaging for liver metastasis detection.

PURPOSE: To compare the accuracy of PET/MR imaging with that of FDG PET/CT and to determine the MR sequences necessary for the detection of liver metastasis using a trimodality PET/CT/MR set-up. METHODS: Included in this single-centre IRB-approved study were 55 patients (22 women, age 61 ± 11 years) with suspected liver metastases from gastrointestinal cancer. Imaging using a trimodality PET/CT/MR set-up (time-of-flight PET/CT and 3-T whole-body MR imager) comprised PET, low-dose CT, contrast-enhanced (CE) CT of the abdomen, and MR with T1-W/T2-W, diffusion-weighted (DWI), and dynamic CE imaging. Two readers evaluated the following image sets for liver metastasis: PET/CT (set A), PET/CECT (B), PET/MR including T1-W/T2-W (C), T1-W/T2-W with either DWI (D) or CE imaging (E), and a combination (F). The accuracy of each image set was determined by receiver-operating characteristic analysis using image set B as the standard of reference. RESULTS: Of 120 liver lesions in 21/55 patients (38%), 79 (66%) were considered malignant, and 63/79 (80%) showed abnormal FDG uptake. Accuracies were 0.937 (95% CI 89.5 - 97.9%) for image set A, 1.00 (95% CI 99.9 - 100.0%) for set C, 0.998 (95% CI 99.4 - 100.0%) for set D, 0.997 (95% CI 99.3 - 100.0%) for set E, and 0.995 (95% CI 99.0 - 100.0%) for set F. Differences were significant for image sets D - F (P < 0.05) when including lesions without abnormal FDG uptake. As shown by follow-up imaging after 50 - 177 days, the use of image sets D and both sets E and F led to the detection of metastases in one and three patients, respectively, and further metastases in the contralateral lobe in two patients negative on PET/CECT (P = 0.06). CONCLUSION: PET/MR imaging with T1-W/T2-W sequences results in similar diagnostic accuracy for the detection of liver metastases to PET/CECT. To significantly improve the characterization of liver lesions, we recommend the use of dynamic CE imaging sequences. PET/MR imaging has a diagnostic impact on clinical decision making.

The Role of 99mTc-antigranulocyte SPECT/CT In Community-Acquired Diabetic Foot Osteomyelitis: A Clinical Experience.

BACKGROUND: Magnetic resonance imaging (MRI) is the actual gold standard for the radiological diagnosis of diabetic foot osteomyelitis (DFO). MATERIALS AND METHODS: MRI is not always available and many patients have contraindications. We evaluated the clinical value of 99mTc-antigranulocyte SPECT/CT (AGS) in eight DFO patients who underwent MRI before. RESULTS: The goal was to have a better clinical view on the extent of bone infection and to ameliorate the surgical approach for DFO. However, this additional scintigraphy did not change anything in the clinical approach. CONCLUSION: We shared our experience with AGS for clinical management of complex DFO cases.

Immunohistochemical Expression Pattern of Theragnostic Targets SSTR2 and PSMA in Endolymphatic Sac Tumors: A Single Institution Case Series.

BACKGROUND: Endolymphatic sac tumors are rare neoplasia characterized by slow growth. However, their clinical impact should not be underestimated, considering their potential for local aggressive behavior and strong association with von Hippel-Lindau syndrome. Therefore, early detection with emerging theragnostic examinations such as 68Ga-DOTATATE-PET/CT might improve patient management and reduce morbidity. METHODS: We report the clinicopathological features of seven endolymphatic sac tumors. In this cohort, we performed immunohistochemical analysis of somatostatin receptor 2A (SSTR2A) and prostate specific membrane antigen (PSMA) protein expression patterns; two targets providing rationale for novel imaging modalities such as PSMA- or SSTR-targeted PET. RESULTS: The tumor cells of all cases were negative for prostate specific membrane antigen and somatostatin receptor 2A, however immunolabeling was consistently detected in intratumoral endothelial cells of endolymphatic sac tumors for PSMA (7/7 cases, 100%), and for SSTR2A (5/7 cases, 71%). CONCLUSIONS: Our results show a high rate of PSMA and SSTR2A expression in the tumor vasculature of endolymphatic sac tumors. PSMA and SSTR2A can be targeted with appropriate radioligands for diagnostic and therapeutic purposes. This finding provides a rationale for prospective clinical studies to test this approach as a sensitive screening tool for patients with suspected endolymphatic sac tumors including an improved management of von Hippel-Lindau syndrome.

FDG-PET-CT/MRI in head and neck squamous cell carcinoma: Impact on pretherapeutic N classification, detection of distant metastases, and second primary tumors.

BACKGROUND: To assess the effect of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the pretherapeutic staging of N classification, detection rate of distant metastases, and second primaries. METHODS: Retrospective study on patients with head and neck carcinoma. We compared pretherapeutic N classification by ultrasound, computed tomography (CT)/magnetic resonance imaging (MRI), and FDG-PET-CT/MRI. RESULTS: A change in the N classification due to FDG-PET-CT/MRI was observed in 116 patients (39.5%) compared to N classification by ultrasound and fine-needle aspiration cytology. Patients with advanced nodal classification (>N2a) were more likely to be reclassified. Distant metastases were detected in 19 patients and a total of 36 second primaries were diagnosed by FDG-PET-CT/MRI. Detection of distant metastases was more likely in regional advanced disease (>N2a). Smokers (>10 py) had a significantly higher risk of second primary. CONCLUSION: FDG-PET-CT/MRI leads to a significant change in pretherapeutic N classification. The cumulative incidence of distant metastases and second primaries was 18.7%.

Hybrid positron emission tomography imaging for initial staging of sinonasal tumors: Total lesion glycolysis as prognosticator of treatment response.

BACKGROUND: To assess hybrid positron emission tomography (PET) imaging in the initial staging and outcome prediction of sinonasal malignancies. METHODS: Retrospective study on patients with sinonasal malignancies undergoing hybrid PET imaging for initial staging. RESULTS: Complete remission (CR) was achieved in 45 of 65 patients (69.2%). Overall sensitivity for detection of primaries using 18F-fluoro-deoxy-d-glucose PET (FDG-PET) was 95.4%, for lymph node metastases 100% and distant metastases (DM) 100%. On univariate analysis, PET parameter total lesion glycolysis (TLG) was associated with achieving CR after primary treatment (176.8 ± 157.2 vs 83.7 ± 110.8, P = .03). Multivariate logistic regression demonstrated that TLG adjusted for the T classification best predicted achievement of CR. CONCLUSIONS: Hybrid PET imaging yields an excellent sensitivity in detecting primary tumors, lymph node metastases and DM in sinonasal malignancies. TLG of the primary tumor is an independent prognostic factor for achieving CR after initial treatment.

Predictive value of suvmax changes between two sequential post-therapeutic FDG-pet in head and neck squamous cell carcinomas.

18-flurodesoxyglucose position emission tomography (FDG-PET) with computed tomography (CT) or magnetic resonance imaging (MRI) is a broadly accepted tool for pretherapeutic staging and post-therapeutic assessment of response. The prognostic value of sequential post-therapeutic FDG-PETs and the impact of change in metabolic activity has been scarcely reported so far. We hypothesized that an increase in metabolic activity (as measured by maximum standardized uptake value, SUVmax) would be predictive for recurrence. We retrospectively assessed all oral, oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma patients treated at the Department of Otorhinolaryngology-Head and Neck Surgery, University Hospital Zurich between April 1st, 2010 and September 30th, 2018 (N = 337). After a negative post-treatment FDG-PET at 3 months, we measured the SUVmax of the local tumor area and the regional lymph nodes on follow-up FDG-PET at 9 months. We then correlated SUVmax difference between 9 and 3 months with tumor recurrence using Kaplan Meier analysis. During follow-up, 68 patients (20.2%) had local recurrence and 53 had regional recurrence (15.7%) at a median time of 9.0 (IQR 4.25-14) and 7.0 (IQR 5.25-23) months, respectively. An increase in local and/or regional SUVmax from the 3 months to the 9 months post-therapeutic FDG-PET resulted in a poorer recurrence-free survival (Log rank, P = 0.001, for both). An increase in local SUVmax between 3 and 9 months was associated with a hazard ratio of 4.17 for recurrence (95%CI 1.89-9.2, P = 0.0003). In conclusion, an increase in metabolic activity/SUVmax between two post-therapeutic FDG-PETs requires a histological examination as it is associated with tumor recurrence.

Diagnostic accuracy of computed tomography and magnetic resonance imaging compared to surgical exploration for anterior skull base and medial orbital wall infiltration in advanced sinonasal tumors.

BACKGROUND: Knowledge of medial orbital wall (MOW) and anterior skull base (ASB) infiltration is of uttermost importance for staging and therapy planning of advanced sinonasal tumors. METHODS: We assessed the diagnostic performance of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) for MOW and ASB infiltration compared to intraoperative exploration. RESULTS: Both CT and MRI yielded higher diagnostic accuracy for MOW infiltration (Reader 1: 83.6% CT; 89.0% MRI, Reader 2: 91.8% CT, 93.2% MRI) than for ASB infiltration (Reader 1: 82.2% CT, 82.2% MRI, Reader 2: 67.7% CT, 67.7% MRI). Both modalities were equal to the gold standard, except for ASB assessment by Reader 2 with MRI. A postoperative change of T classification is common (Reader 1: 28.8%, Reader 2: 31.5%). CONCLUSIONS: CT and MRI are accurate methods for the assessment of MOW infiltration. ASB assessment is challenging and false-positive and false-negative findings are common with both methods, emphasizing the need for intraoperative exploration.

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23.

The authors would like to make a correction to their published paper [1][...].

Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma.

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning.

Tumor cell viability in salvage neck dissections: Poor prognosis predicted by high postradiation nodal SUVmax , p16-negativity, and low nodal shrinkage.

BACKGROUND: After primary chemoradiation in advanced oropharyngeal, laryngeal, and/or hypopharyngeal cancer, nodal disease may require a salvage neck dissection. However, salvage neck dissection is associated with increased morbidity and may only be necessary in case of persistence of viable tumor cells, which can be difficult to confirm and virtually impossible to exclude by fine needle aspiration cytology. We, therefore, aimed to identify predictive factors for the persistence of viable tumor cells in lymph node metastases from head and neck squamous cell cancer after chemoradiation. METHODS: We performed a retrospective review of neck dissection specimens performed after primary (chemo-)radiation for oropharyngeal, laryngeal, or hypopharyngeal squamous cell carcinoma. All patients were treated at University Hospital Zurich from 2007 to 2016. RESULTS: A total of 78 patients were included. Thirty-eight patients (48.7%) had viable tumor cells in their neck dissection sample. High postradiation nodal maximum standardized uptake value (SUVmax ), p16 negativity, and low nodal shrinkage were predictors of viable tumor cells in salvage neck dissections (Mann-Whitney U/chi-squared test, P < .001, P = .025, and P = .042, respectively). Patients with viable tumor cells showed a significantly worse locoregional recurrence-free survival, distant metastasis-free survival, and disease-specific survival (log-rank test, P < .001). CONCLUSIONS: Viable tumor cells can be predicted by high residual metabolic activity in the lymph nodes, negative p16 status, and low nodal shrinkage. Viable tumor cells in neck dissection specimens are associated with a poor survival and provide important prognostic information.

The potential of machine learning to predict postoperative pancreatic fistula based on preoperative, non-contrast-enhanced CT: A proof-of-principle study.

BACKGROUND: Postoperative pancreatic fistula remains an unsolved challenge after pancreatoduodenectomy. Important in this regard is the presence of a soft pancreatic texture which is a major risk factor. Advances in machine learning and texture analysis of medical images allow identification of features of parenchyma that are invisible to the human eye. The aim of this study was to investigate the potential of machine learning to predict postoperative pancreatic fistula based on preoperative, non-contrast-enhanced computed tomography. METHODS: We screened a prospectively assessed database including all patients undergoing pancreatoduodenectomy at a tertiary center from 2008 until 2018 for patients based on the occurrence of postoperative pancreatic fistula. In total, 110 patients were included, consisting of 55 patients who developed a postoperative pancreatic fistula and 55 without postoperative pancreatic fistula. For machine learning-based texture analysis preoperative, non-contrast-enhanced computed tomography axial images were used. Machine learning results were tested using 10-fold cross validation. Previously validated clinical fistula risk scores (original and alternative fistula risk scores) served as reference tests. RESULTS: Both the original and the alternative fistula risk scores showed good discrimination between patients without and with postoperative pancreatic fistula (area under the curve 0.76 and 0.72, respectively). Machine learning-based texture analysis showed potential to detect histologic fibrosis (area under the curve 0.84, sensitivity 75%; specificity 92%), histologic lipomatosis (area under the curve 0.82, sensitivity 78%; specificity 89%), and intraoperative pancreatic hardness (area under the curve 0.70, sensitivity 78%; specificity 74%). The features of the machine learning-based texture analysis were most accurate in predicting the occurrence of postoperative pancreatic fistula (area under the curve 0.95, sensitivity of 96%; specificity 98%) after pancreatoduodenectomy. CONCLUSION: This proof-of-principle study suggests the ability of machine learning in recognizing important features of pancreatic texture associated with an increased risk of postoperative pancreatic fistula based on preoperative computed tomography.

Predictive Value of Pretherapeutic Maximum Standardized Uptake Value (Suvmax) In Laryngeal and Hypopharyngeal Cancer.

The aim of the study was to evaluate whether pretherapeutic metabolic tumor parameters from 18-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging could predict larynx preservation in laryngeal and hypopharyngeal cancer patients prior to primary chemoradiation. Tumor metabolic parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were retrospectively assessed in a consecutive cohort of laryngeal and hypopharyngeal cancer patients undergoing primary (chemo-)radiation. Main outcome measures were larynx preservation and survival. The study included 97 patients with a median follow-up of 32 months (IQR 20-54.5). For hypopharyngeal cancer, multivariable analysis showed that patients with a primary tumor's SUVmax > 9.5 entailed a higher risk of undergoing salvage pharyngolaryngectomy after chemoradiation (HR = 8.64, 95% CI = 1.1-67.3, P = 0.040). In laryngeal cancer, SUVmax did not predict the need for salvage laryngectomy. The only predictor for larynx preservation in laryngeal cancer patients was T-classification at initial diagnosis (HR = 6.67, 95% CI = 0.82-53.9, P = 0.039). In conclusion, SUVmax of primary tumor could be used as a predictor of larynx preservation prior to primary chemoradiation in hypopharyngeal cancer patients. This information may be important for patient counseling, as high SUVmax was correlated with reduced probability of larynx preservation. However, in laryngeal cancer patients, SUVmax does not seem to be predictive of outcome.