[18F]FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumab.

Background Immune checkpoint inhibitors have changed the paradigm of cancer treatment; however, non-invasive biomarkers of response are still needed to identify candidates for non-responders. We aimed to investigate whether immunotherapy [18F]FDG PET radiomics signature (iRADIOMICS) predicts response of metastatic non-small-cell lung cancer (NSCLC) patients to pembrolizumab better than the current clinical standards. Patients and methods Thirty patients receiving pembrolizumab were scanned with [18F]FDG PET/CT at baseline, month 1 and 4. Associations of six robust primary tumour radiomics features with overall survival were analysed with Mann-Whitney U-test (MWU), Cox proportional hazards regression analysis, and ROC curve analysis. iRADIOMICS was constructed using univariate and multivariate logistic models of the most promising feature(s). Its predictive power was compared to PD-L1 tumour proportion score (TPS) and iRECIST using ROC curve analysis. Prediction accuracies were assessed with 5-fold cross validation. Results The most predictive were baseline radiomics features, e.g. Small Run Emphasis (MWU, p = 0.001; hazard ratio = 0.46, p = 0.007; AUC = 0.85 (95% CI 0.69-1.00)). Multivariate iRADIOMICS was found superior to the current standards in terms of predictive power and timewise with the following AUC (95% CI) and accuracy (standard deviation): iRADIOMICS (baseline), 0.90 (0.78-1.00), 78% (18%); PD-L1 TPS (baseline), 0.60 (0.37-0.83), 53% (18%); iRECIST (month 1), 0.79 (0.62-0.95), 76% (16%); iRECIST (month 4), 0.86 (0.72-1.00), 76% (17%). Conclusions Multivariate iRADIOMICS was identified as a promising imaging biomarker, which could improve management of metastatic NSCLC patients treated with pembrolizumab. The predicted non-responders could be offered other treatment options to improve their overall survival.

18F-FDG PET/CT for Staging and Evaluation of Therapy in a Patient With Unusual Hairy Cell Leukemia Presentation.

Hairy cell leukemia is a rare hematologic malignancy characterized by splenomegaly, pancytopenia, and susceptibility to infections. We report a case of a 66-year-old man, diagnosed with hairy cell leukemia, without severe cytopenias and splenomegaly, but with an extensive pathological retroperitoneal mass and infiltration of the spleen and skeletal involvement. All findings were highly avid on pretreatment F-FDG PET/CT scan. Treatment response evaluation F-FDG PET/CT scan showed normalization of FDG uptake on all previously pathological sites.

Granulomatosis after autologous stem cell transplantation in nonHodgkin lymphoma - experience of single institution and a review of literature.

BACKGROUND: Sarcoidosis before and after treatment of malignancy is an important differential diagnosis that has to be distinguished from lymphoma. PATIENTS AND METHODS: Hodgkin lymphoma, diffuse large B-cell lymphoma and aggressive follicular lymphoma are being staged and treatment effect is evaluated with PET-CT. We report three cases of aggressive lymphoma after high dose therapy and autologous stem cell transplantation with positive lymph nodes on PET-CT, which were histologically diagnosed as sarcoidosis/granulomatosis. In the literature, we found that false positive lymph nodes were more common after allogeneic than after autologous transplantation. CONCLUSIONS: Post-treatment PET-CT positive lymph nodes should always be examined histologically prior to any further treatment decision to avoid unnecessary toxic procedures.

Thyroid lesions incidentally detected by (18)F-FDG PET-CT - a two centre retrospective study.

BACKGROUND: Incidental (18)F-FDG uptake in the thyroid on PET-CT examinations represents a diagnostic challenge. The maximal standardized uptake value (SUVmax) is one possible parameter that can help in distinguishing between benign and malignant thyroid PET lesions. PATIENTS AND METHODS: We retrospectively evaluated (18)F-FDG PET-CT examinations of 5,911 patients performed at two different medical centres from 2010 to 2011. If pathologically increased activity was accidentally detected in the thyroid, the SUVmax of the thyroid lesion was calculated. Patients with incidental (18)F-FDG uptake in the thyroid were instructed to visit a thyroidologist, who performed further investigation including fine needle aspiration cytology (FNAC) if needed. Lesions deemed suspicious after FNAC were referred for surgery. RESULTS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% - in 230 out of 5,911 patients investigated on PET-CT. Malignant thyroid lesions (represented with focal thyroid uptake) were detected in 10 of 66 patients (in 15.2%). In the first medical centre the SUVmax of 36 benign lesions was 5.6 ± 2.8 compared to 15.8 ± 9.2 of 5 malignant lesions (p < 0.001). In the second centre the SUVmax of 20 benign lesions was 3.7 ± 2.2 compared to 5.1 ± 2.3 of 5 malignant lesions (p = 0.217). All 29 further investigated diffuse thyroid lesions were benign. CONCLUSIONS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% of patients who had a PET-CT examination. Only focal thyroid uptake represented a malignant lesion in our study - in 15.2% of all focal thyroid lesions. SUVmax should only serve as one of several parameters that alert the clinician on the possibility of thyroid malignancy.

A patient with a painless neck tumour revealed as a carotid paraganglioma: a case report.

Carotid paragangliomas are usually slowly enlarging and painless lateral neck masses. These mostly benign lesions are recognized due to their typical location, vessel displacement and specific blood supply, features that are usually seen on different imaging modalities. Surgery for carotid paraganglioma can be associated with immediate cerebrovascular complications or delayed neurological impairment.We are reporting the case of a 36-year-old man who presented with a painless mass on the right side of his neck 11 months after being treated for testicular cancer. After a fine-needle aspiration biopsy, he was diagnosed with a testicular cancer lymph node metastasis. Neck US and fluorine [F-18]-fluorodeoxy-D-glucose (FDG) PET-CT showed no signs of hypervascularity or vessel displacement. The patient underwent a level II to V functional neck dissection. During the procedure, suspicion of a carotid paraganglioma was raised and the tumour was carefully dissected from the walls of the carotid arteries with minimal blood loss and no cranial nerve dysfunction.The histology report revealed carotid paraganglioma with no metastasis in the rest of the lymph nodes. The patient's history of testicular germ cell tumour led to a functional neck dissection during which a previously unrecognized carotid paraganglioma was removed.Surgery for carotid PG can be associated with complications that have major impact on quality of life. A thorough assessment of the patient and neck mass must therefore be performed preoperatively in order to perform the surgical procedure under optimal conditions.

Neoadjuvant chemotherapy in 29 patients with locally advanced follicular or Hürthle cell thyroid carcinoma: a phase 2 study.

BACKGROUND: It is believed that chemotherapy (ChT) is ineffective in follicular thyroid carcinoma (FTC) and Hürthle cell thyroid carcinoma (HCTC). The aim of our retrospective study was to find out whether neodjuvant ChT before thyroid surgery had any effect on the size of primary tumor in patients with FTC or HCTC. METHODS: The study included 29 patients (20 women, 9 men; mean age: 60.8 years) with FTC or HCTC who had T3 or T4 tumor and were treated with neoadjuvant ChT from 1979 to 2004. A mean tumor diameter was 9.3 cm. Extrathyroid growth of tumor was present in 15 patients. Regional and distant metastases were detected in 6 and 12 patients, respectively. With respect to the site of metastatic spread, the lung was involved in eight patients and the skeleton in five. ChT consisted of vinblastine in 19 cases, vinblastine with adriamycin in 5 cases, or other ChT regimens in 5 cases. RESULTS: Altogether, 67 cycles of ChT were given and tumor size decreased by >50% in 13 patients (=45%). ChT was effective in patients with FTC and HCTC in 47% and 43%, respectively. In the patients with and without distant metastases, the primary tumor size decreased by >50% in 17% and 65% (p=0.02), respectively. R0, R1, and R2 resection was performed in 15, 10, and 4 cases, respectively. Histopathology revealed that ChT (i.e., wide areas of tumor necrosis) was effective in seven patients (24%). The 5- and 10-year cause-specific survivals of the patients were 77% and 47%, while the 5- and 10-year disease-free intervals were 57% and 46%, respectively. Six patients are alive (median survival: 162 months), four of them have no evidence of disease, six patients died of other causes (median survival: 101 months), while 17 patients died of FTC or HCTC (median survival: 72 months). Among them, 16 died of distant metastases, while only one succumbed to locoregional recurrence and distant metastases. CONCLUSIONS: ChT before surgical procedure may be effective in order to decrease the tumor size in FTC or HCTC in 45% of patients.

Recombinant human thyrotropin-aided radioiodine therapy in patients with metastatic differentiated thyroid carcinoma.

Our aim was to test the efficacy of 131-I therapy (RIT) using recombinant human TSH (rhTSH) in patients with differentiated thyroid carcinoma (DTC) in whom endogenous TSH stimulation was not an option due to the poor patient's physical condition or due to the disease progression during L-thyroxin withdrawal. The study comprised 18 patients, who already have undergone total or near-total thyroidectomy and radioiodine ablation and 0-12 (median 5) RITs after L-thyroxin withdrawal. Our patients received altogether 44 RITs using rhTSH while on L-thyroxin. Six to 12 months after the first rhTSH-aided RIT, PR and SD was achieved in 3/18 (17%) and 4/18 patients (22%), respectively. In most patients (n = 12; 61%) disease progressed despite rhTSH-aided RITs. As a conclusion, rhTSH-aided RIT proved to add some therapeutic benefit in 39% our patients with metastatic DTC, who otherwise could not be efficiently treated with RIT.

Role of serum S100B and PET-CT in follow-up of patients with cutaneous melanoma.

BACKGROUND: Increased level of serum S100B can serve as a marker of metastatic spread in patients with cutaneous melanoma (CM). In patients with elevated S100 B and/or clinical signs of disease progression PET-CT scan is a valuable tool for discovering metastases and planning treatment.The aims of this study were to determine whether regular measurements of serum S100B are a useful tool for discovering patients with CM metastases and to evaluate the diagnostic value of PET-CT during the follow-up. METHODS: From September 2007 to February 2010, 115 CM patients included in regular follow up at the Institute of Oncology Ljubljana were appointed to PET-CT. There were 82 (71.3%) patients with clinical signs of disease progression and 33 (28.7%) asymptomatic patients with two subsequent elevated values of S100B. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) of S100B and PET-CT were calculated using standard procedures. RESULTS: Disease progression was confirmed in 81.7% of patients (in 86.5% of patients with clinical signs of disease progression and in 69.7% of asymptomatic patients with elevated S100B). Sensitivity, specificity, PPV and NPV of S100B was 33.8%, 90.9%, 96.0% and 17.5% in patients with clinical signs of disease progression. In 20.0% of patients increased serum S100B was the only sign of disease progression. Sensitivity and PPV of S100 in this group of patients were 100.0% and 69.7%.With PET-CT disease progression was diagnosed in 84.2% of symptomatic patients and in 72.7% of asymptomatic patients with elevated S100B. The sensitivity, specificity, PPV and NPV of PET-CT for symptomatic patients was 98.5%, 90.9%, 98.5% and 90.9% and 100%, 90.0%, 95.8% and 100% for asymptomatic patients with elevated S100. CONCLUSIONS: Measurements of serum S100B during regular follow-up of patients with CM are a useful tool for discovering disease progression in asymptomatic patients. The value of its use increases if measurements are followed by extended whole body PET-CT.

Axillary recurrence rate in breast cancer patients with negative sentinel lymph node.

AIM: To assess the axillary recurrence rate in operable breast cancer patients with clinically negative axilla after negative sentinel lymph node in whom axillary lymph node dissection had not been performed. METHODS: Fifty consecutive female operable breast cancer patients with negative sentinel lymph node biopsy in whom axillary lymph node dissection had not been performed were included in the study and prospectively followed, with median follow-up time of 32 months (range 10-50 months). Sentinel lymph node biopsy was performed by the triple method. RESULTS: The sentinel node identification rate was 100%. In only one of 50 patients with negative sentinel lymph node, axillary recurrence developed 26 months after surgery. This was the sole patient with sentinel lymph node biopsy after previous surgical biopsy. After treatment, all patients were alive and with no evidence of disease. CONCLUSIONS: Omitting axillary node dissection after negative sentinel node biopsy in operable breast cancer patients proved to be safe. Patients with previous open surgical biopsy should be given special attention in the follow-up.

Columnar cell thyroid carcinoma - diagnostic dilemmas and pitfalls.

BACKGROUND: Columnar cell carcinoma is a rare variant of papillary thyroid carcinoma associated with aggressive clinical behaviour. A CASE REPORT: of a 34-year-old male patient, who presented with the rapidly growing mass in the neck, extending to the anterior and middle mediastinum, tightly closing the upper thoracic apperture and causing tracheal and oesophageal deviation, with minimal compression and stenosis. A diagnosis of columnar cell carcinoma, arising from the ectopic thyroid tissue just adjacent to the left thyroid lobe was based on histological and intraoperative findings. Near total thyroidectomy and lymph-node dissection were followed by external beam radiotherapy of the neck and mediastinum, chemotherapy and radioiodine ablation of the remaining functional thyroid tissue. Pre-and post-operative radionuclide imaging (99mTc(V)-DMSA, 99mTc-MIBI, 123-I-mIBG and Octreoscan findings are discussed, with a special emphasis given to the dilemmas in histological characterisation of the tumor, the problems in therapeutic approach and the dilemmas and pitfalls in the interpretation of radionuclide findings in this patient, especially the ones performed post radiotherapy of the neck and mediastinum.

The value of radionuclide studies in children with autosomal recessive polycystic kidney disease.

PURPOSE: To describe and analyze the appearances of autosomal recessive polycystic kidney disease (ARPKD) on Tc-99m DMSA and Tc-99m HIDA scintigraphy. MATERIALS AND METHODS: The authors evaluated scintigraphic findings for 13 boys and 9 girls (age range, 2 months to 22.75 years; mean, 7.5 years) with ARPKD. Fourteen children underwent Tc-99m DMSA and 20 underwent Tc-99m HIDA scintigraphy according to European guidelines. Kidney outline, internal structure, tracer uptake, and differential function were analyzed on Tc-99m DMSA images, whereas relative liver lobe sizes, hepatocyte tracer uptake, time to peak, and excretion into the biliary tree and gut were evaluated on Tc-99m HIDA scans. RESULTS: On Tc-99m DMSA images, loss of kidney outline and internal structure was seen in 75% of the scans, and patchy tracer uptake with focal defects throughout the kidneys, particularly at the poles, was evident in 93%. In 85% of the cases, the Tc-99m DMSA changes did not correlate with the ultrasonographic findings where the kidneys are uniformly affected. Characteristic findings on Tc-99m HIDA scans were enlarged left liver lobe in 80%, a delay in maximal hepatocyte uptake in 68%, delayed tracer excretion into the biliary tree in 32% (with stasis in the prominent intrahepatic biliary ducts in 50% or pooling into the segmentally dilated biliary ducts in 25%), and delayed excretion into the gut in 40% of patients. CONCLUSIONS: In a child with clinically enlarged kidneys that appear diffusely hyperechoic on ultrasound, the appearances on Tc-99m DMSA imaging strongly support the diagnosis of ARPKD. The Tc-99m HIDA findings, especially of an enlarged left lobe of the liver with bile stasis or dilatation, further support the diagnosis.