Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS).

BACKGROUND: Classical Kaposi sarcoma (cKS) is a rare human herpesvirus 8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab in patients with previously treated progressive cKS. PATIENTS AND METHODS: cKS patients with progressive disease after one or more lines of systemic therapy and measurable disease by positron emission tomography/computed tomography and/or physical examination received nivolumab 240 mg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks until progression or toxicity for a maximum of 24 months. The primary endpoint was overall response rate; secondary endpoints included 6-month progression-free survival (PFS) rate and safety. Immune correlates were explored using immunohistochemistry, DNA sequencing (596/648 genes) and RNA sequencing (whole transcriptome hybrid capture) of tumor specimens and matched blood. RESULTS: Eighteen male patients (median age 76.5 years) were enrolled between April 2018 and December 2020. At a median follow up of 24.4 months, overall response rate by RECIST v1.1 was 87%. Metabolic complete response as assessed by positron emission tomography/computed tomography was observed in 8 of 13 (62%) assessable patients. Some 6/13 achieved pathological complete response after treatment. In two patients, palliative limb amputation was prevented. Median PFS was not reached. The 6- month and 12-month PFS rate was 76.5% and 58.8%, respectively. Only four patients (22%) experienced grade 3-4 adverse events. The most frequent genomic alteration was biallelic copy number loss of the FOX1A gene. The majority of tumors carried a low tumor mutational burden, were microsatellite stable, mismatch repair proficient, did not express programmed death-ligand 1, and displayed only low lymphocytic infiltrates, rendering them immunologically 'cold'. CONCLUSIONS: This prospectively designed phase II study of nivolumab and ipilimumab demonstrates promising activity of this combination in progressive cKS representing a new treatment option in this population.

The yield of F18 FDG PET-CT for the investigation of fever of unknown origin, compared with diagnostic CT.

BACKGROUND: 18F-Fluoro-2-deoxy-D-glucose (FDG) positron emission tomography, with contrast enhanced CT (PET-CT), is recommended as a first or a second-line imaging method for the evaluation of patients with fever of unknown origin (FUO). We evaluated the yield of PET-CT vs. contrast enhanced CT (alone) for the diagnosis of classical FUO. METHODS: A single center, 8-year retrospective cohort study. All hospitalized patients who underwent PET-CT for the investigation of classical FUO between 1/2012-1/2020 were included. The final diagnosis, based on clinical, microbiological, radiological and pathological data available at the latest follow-up, at least six months after discharge, was determined. For each case, we determined whether the diagnosis would have been reached based on the CT scan alone, or based on the PET-CT (thus, defining PET-CT as necessary). We compared the overall sensitivity and specificity results for both PET-CT and CT scan. Variables that were found to be significantly associated with PET-CT necessity on univariable analysis were entered into a multivariable logistic regression analysis. The results of the regression model were reported in odds ratios (OR) and 95% confidence intervals (CI). RESULT: A total of 303 patients with classical FUO were referred for PET-CT. The final diagnoses included infectious diseases in 111/303 patients (36.5%), malignancies in 56/303 patients (18.4%) and non-infectious inflammatory conditions in 52/303 patients (17.1%). FUO resolved without diagnosis in 84/303 patients (28%). The overall sensitivity and specificity of the PET-CT scans were 88.7% and 80.9%, respectively, and for the CT scans were 75.2% and 90.2%, respectively. PET-CT had superior sensitivity vs CT (p=0.00) for all subgroups, with generally decreased specificity than CT for infections and inflammatory conditions. PET-CT was determined as necessary in 26% (79/303) of the patients. Endovascular infection, hematological malignancy and large vessel vasculitis were the only factors associated with PET-CT necessity on multivariable analysis. CONCLUSIONS: PET-CT offers superior sensitivity with slightly decreased specificity for the diagnosis of classical FUO compared to diagnostic CT. We recommend PET-CT as the imaging modality of choice for patients with classical FUO, when endovascular infection, hematological malignancy or large vessel vasculitis are suspected.

Quantitative biomarkers for liver metastases: comparison of MRI diffusion-weighted imaging heterogeneity index and fluorine-18-fluoro-deoxyglucose standardised uptake value in hybrid PET/MR.

AIM: To investigate the ability of apparent diffusion coefficient (ADC) heterogeneity index to discriminate liver metastases (LM) from normal-appearing liver (NAL) tissue as compared to common magnetic resonance imaging (MRI) metrics, and to investigate its correlation with 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET) standardised uptake value (SUV). MATERIALS AND METHODS: Thirty-nine liver metastases in 24 oncology patients (13 women, 11 men; mean age 56±13 years) with proven LM from heterogeneous sources were evaluated on a PET/MRI system. Abdominal sequences included Dixon and diffusion-weighted imaging (DWI) protocols with simultaneous PET. Tissue heterogeneity was calculated using the coefficient of variance (CV) of the ADC, and compared in LM and in NAL tissue of the same volume in an adjacent portion of the liver. The correlations between various ADC measures and PET SUV in distinguishing LM from NAL were evaluated. RESULTS: A good correlation was found between ADCcv and SUVpeak (r=0.712). Moderate inverse correlation was found between ADCmin and SUVpeak (r=-0.536), and a weak inverse correlation between ADCmean and SUVpeak (r=-0.273). There was a significant difference between LM and NAL when ADCcv (p<0.0001) and ADCmin (p=0.001) were used. Receiver operating characteristic (ROC) analysis of SUV, ADCcv, ADCmin, and ADCmean produced an AUC of 0.989, 0.900, 0.742, and 0.623 respectively. CONCLUSIONS: The ADCcv index is a potential biomarker of LM with better correlation to 18F-FDG PET SUVpeak than conventional MRI metrics, and may serve to quantitatively discriminate between LM and NAL.

Early 68GA-PSMA PET/MRI acquisition: assessment of lesion detectability and PET metrics in patients with prostate cancer undergoing same-day late PET/CT.

AIM: To compare lesion detectability and positron-emission tomography (PET) metric measurements between early-PET/magnetic resonance imaging (MRI) acquisition and same-day PET/computed tomography (CT). MATERIALS AND METHODS: The study was approved by the institutional review board and written informed consent was obtained from all patients. Twenty-one patients underwent non-time-of-flight (TOF) PET/MRI immediately following 68GA-prostate-specific membrane antigen (PSMA) tracer injection in two steps: firstly, early prostate PET/MRI (pPET/MRI) and early whole-body (WB) PET/MRI (wbPET/MR) followed by WB TOF PET/CT (wbPET/CT). Lesion detectability was compared between wbPET/MRI and wbPET/CT while PET metric measurements were compared between pPET/MR, wbPET/MRI, and wbPET/CT. RESULTS: Sixty-one and 63 lesions were found on wbPET/MRI and wbPET/CT, respectively (K=0.95, 95% confidence interval (CI)=0.89-1.0) with very good correlation between PET metric measurements (r=0.91; p=0.001). Bland-Altman plots demonstrated a mean percentage difference between wbPET/CT with wbPET/MRI of 34.4% with 95% limits of agreement (LOA) between -39% to 107.9% for metabolic tumour volume (MTV) and a mean difference of 30% with LOA between -13.4% to 73.4% for peak standardised uptake value (SUVpeak). CONCLUSION: Early PET/MRI demonstrates very good lesion detectability agreement and correlation with PET metrics compared to same-day PET/CT. Nevertheless, LOA are far beyond the clinically acceptable range, and therefore, PET/CT and early PET/MRI metrics cannot be used interchangeably.

The Role of 18F-FDG PET/CT on Staging and Prognosis in Patients with Small Cell Lung Cancer.

BACKGROUND: We evaluated 18F-FDG PET/CT in small cell lung cancer (SCLC) staging and assessed metabolic (SUVmax, MTV and TLG) and morphologic (CTvol) variables as predictors for overall survival (OS) and progression-free survival (PFS). METHODS: Patients with newly diagnosed, histopathology-confirmed SCLC, who underwent 18F-FDG PET/CT were evaluated. A Cox proportional hazard model was used to determine the association between the primary tumour SUVmax, MTV, TLG and CTvol with OS and PFS. Similar evaluations were performed when hilar/mediastinal lymphadenopathy was included [total SUVmax (TSUVmax), total MTV (TMTV) and total TLG (TTLG)]. RESULTS: 55 patients were included. 18F-FDG PET/CT changed staging in 6/55 (10.9%) patients who were upstaged to extensive disease. TTLG (>443.8) was a significant variable for OS with HR=2.1 (CI 1.14-3.871, p=0.017). Patients with TTLG>443.8 had a median OS of 13.4 months compared to 25.7 months in patients with TTLG<443.8 (p=0.018). TMTV (>72.4) was significant for PFS with HR=2.3 (CI 1.11-4.8, p=0.025). A median PFS of 12.1 and 26.2 months was found with TMTV greater and less than 72.4, respectively (p=0.005). CONCLUSIONS: 18F-FDG PET/CT improved staging of patients with SCLC, and TTLG and TMTV can be used as prognostic variables for OS and PFS, respectively. KEY POINTS: • Identifying variables that predict the prognosis of patients with SCLC is important. • 18F-FDG PET/CT influences staging of patients with SCLC. • Metabolic parameters could be used as predictors for PFS and OS.

Survival Prognostic Value of Morphological and Metabolic variables in Patients with Stage I and II Non-Small Cell Lung Cancer.

BACKGROUND: The prognosis of patients with non-small cell lung cancer (NSCLC) is important, as patients with resectable disease and poor prognostic variables might benefit from neoadjuvant therapy. The goal of this study is to evaluate SUVmax, SUVmax ratio, CT volume (CTvol), metabolic tumour volume (MTV) and total lesion glycolisis (TLG) as survival prognostic markers. In addition, we defined two variables; MTV x SUVmax (MTVmax) and CTvol x SUVmax (CTvolmax) and assessed whether they can be used as prognostic markers. METHODS: Patients with stage I-II NSCLC who underwent 18 F FDG PET/CT and surgery were evaluated. Cox proportional-hazard model was used to determine the association between variables and survival. Similar analysis was performed in cases with no lymph node (LN) involvement. RESULTS: One hundred and eighty-one patients were included (at the end of the study, 140 patients were alive). SUVmax with a cut-off value of 8.2 was significant survival prognostic factor regardless of LN involvement (P = 0.012). In cases with no LN involvement, SUVmax and CTvol (≥7.1 ml) were significant survival prognostic factors with P = 0.004 and 0.03, respectively. CONCLUSIONS: SUVmax may be a useful prognostic variable in stage I-II NSCLC while morphologic tumour volume might be useful in cases with no lymph node involvement. KEY POINTS: • Identifying variables that predict the prognosis of patients with NSCLC is important. • SUVmax in primary lung tumour is a useful independent prognostic variable. • (CTvol) is an independent prognostic variable if no lymph nodes are involved.

The value of 18-FDG PET/CT in the diagnosis and management of implant-related infections of the tibia: a case series.

BACKGROUND: Positron emission tomography (PET) combined with Computerised Tomography (CT) is gaining ground in clinical settings due to its added value of combined metabolic and anatomical imaging. PET/CT has shown promising results in diagnosing both acute and chronic infection of the axial and appendicular skeleton. PET imaging has an advantage in patients with metallic implants because FDG uptake, in contrast to magnetic resonance imaging (MRI) and standard computed tomography (CT), is not hampered by metallic artifacts. The role of PET/CT in the evaluation of implant-related infections involving the tibia in particular has not been thoroughly studied. PURPOSE: To investigate the usefulness of 18-FDG PET/CT in the diagnosis and treatment of implant-related infections of the tibia following osteosynthesis. METHODS: We reviewed 10 patients who underwent internal fixation to the tibia following trauma (4 open fractures, 6 closed fractures) and presented later with clinical signs of a possible implant-related infection. In evaluating the patients we used standard work-up methods (standard radiographs, lab tests) as well as advanced imaging techniques (PET/CT) in order to confirm the diagnosis and decide upon the preferred treatment. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were then calculated for PET/CTs ability to predict presence of infection using intraoperative cultures as the gold standard. RESULTS: PET/CT validated our working diagnosis 9 out of 10 patients. In particular, it helped distinguish between: infected nonunion (n=4), aseptic nonunion (n=1), soft tissue infection (n=2) and chronic osteomyelitis (n=3). The overall sensitivity and specificity of PET/CT for identifying an osseous infection were 85.7% and 100%, respectively. The PPV and NPV were 100% and 75%, respectively. CONCLUSION: PET/CT is a promising imaging modality that can aid in the work up of patients with suspected implant-related infections of the tibia following osteosynthesis, and may be used as a supportive measure in clinical decision making.

The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis.

The exact incidence of extra-cardiac complications (ECC) in patients with infective endocarditis (IE) is unknown but presumed to be high. These patients, although mostly asymptomatic, may require a more aggressive therapeutic approach. (18)fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used for the diagnosis of infections, but its role in the early diagnosis of IE complications is still unclear. This study aimed to evaluate the role of FDG-PET/CT in the early diagnosis of ECC in IE and its implications for medical management. We prospectively studied 40 consecutive patients with a confirmed diagnosis of IE (according to the modified Duke criteria) who underwent a whole body FDG-PET/CT study within 14 days from diagnosis. The FDG-PET/CT demonstrated ECC in 17 (42.5%) patients, while 8 (38.1%) of them were asymptomatic. The most frequent embolic sites were musculoskeletal and splenic. Owing to the FDG-PET/CT findings, treatment planning was modified in 14 (35%) patients. This included antibiotic treatment prolongation (27.5%), referral to surgical procedures (15%) and, most substantially, prevention of unnecessary device extraction (17.7%). According to our experiences, FDG-PET/CT imaging was useful in the detection of embolic and metastatic infections in IE. This clinical information had a significant diagnostic and therapeutic impact in managing IE disease.

[18F]FDG-PET/CT for the diagnosis of patients with fever of unknown origin.

BACKGROUND AND AIMS: The diagnosis of patients with fever of unknown origin (FUO) remains a challenging medical problem. We aimed to assess the diagnostic contribution of 18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET)/computed tomography (CT) for the evaluation of FUO. METHODS: We performed a 4-year retrospective single-center study of all hospitalized patients that underwent FDG-PET/CT for evaluation of FUO. The final diagnosis of the febrile disease was based on clinical, microbiological, radiological and pathological data available at the final follow-up. Predictors for a contributory exam were sought. RESULTS: One hundred and twelve patients underwent FDG-PET/CT for the investigation of FUO in the years 2008-2012 and were included in the study. A final diagnosis was determined in 83 patients (74%) and included: infectious disease in 49 patients (43%), non-infectious inflammatory disease in 17 patients (16%), malignancies in 15 patients (14%), other diagnoses in 2 patients (1.7%), FUO resolved with no diagnosis and no evidence of disease during a 6-month follow-up in 23 patients (20%), and death with fever and with no diagnosis in 6 patients (5%). Seventy-four FDG-PET/CT studies (66%) were considered clinically helpful and contributory to diagnosis (46% positive contributory value and 20.5% contributory to exclusion of diagnosis). PET/CT had a sensitivity of 72.2%, a specificity of 57.5%, a positive predictive value (PPV) of 74.2% and a negative predictive value (NPV) of 53.5%. On multivariable analysis, significant predictors of a positive PET/CT contributory to diagnosis were a short duration of fever and male gender. CONCLUSIONS: PET/CT is an important diagnostic tool for patients with FUO.

Comparison of 80 and 120 kVp contrast-enhanced CT for attenuation correction in PET/CT, using quantitative analysis and reporter assessment of PET image quality.

AIM: To determine the effect of low tube voltage on positron-emission tomography (PET) image quality, quantitative analysis, and radiation dose in a combined PET/computed tomography (CT) study in patients with normal body mass index (BMI). MATERIALS AND METHODS: One hundred and twenty-nine examinations performed in 46 patients (mean age 57 years), who had at least two separate studies were retrospectively evaluated; at least one with 120 kVp and one with 80 kVp. Three independent readers reviewed all PET images and graded the image quality. PET signal and noise were recorded on the liver, spleen, fat, bone marrow, and aorta. CT dose index (CTDI) and the dose-length product (DLP) were used for CT radiation dose estimation. A mixed-effects model analysis was used for comparison of estimated radiation dose and PET data. RESULTS: There was a significant decrease of 15% in the radiation dose estimates between 80 and 120 kVp (DLP 946.2 ± 189 versus 1157.0 ± 236, respectively; p < 0.001). There was an increase of 12% in PET signal in the normal liver with 80 kVp. The average score of PET image quality obtained between 80 and 120 kVp was 4.85 ± 0.42 versus 4.90 ± 0.27, respectively (p = 0.47). CONCLUSION: PET/80 kVp CT has no statistically significant difference in the PET image quality and quantitative analysis compared to PET/120 kVp and may be used in selected patients to reduce the radiation dose.