Dynamic FDG-PET/CT in the Initial Staging of Primary Breast Cancer: Clinicopathological Correlations.

Our aim was to evaluate correlation between clinicopathological features (clinical T and clinical N stages; histological type; nuclear grade; hormone-receptor and HER2 status, proliferation activity and tumor subtypes) of breast cancer and kinetic parameters measured by staging dynamic FDG-PET/CT examinations. Following ethical approval and patients' informed consent we included 34 patients with 35 primary breast cancers in our prospective study. We performed dynamic PET imaging, and assessed plasma activity noninvasively. To delineate primary tumors we applied a frame-by-frame semi-automatic software-based correction of motion artefacts. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). We found that k3, Ki and MRFDG were significantly higher in higher grade (p = 0.0246, 0.0089 and 0.0076, respectively), progesterone-receptor negative (p = 0.0344, 0.0217 and 0.0132) and highly-proliferating (p = 0.0414, 0.0193 and 0.0271) tumors as well as in triple-negative and hormone-receptor negative/HER2-positive subtypes (p = 0.0310, 0.0280 and 0.0186). Ki and MRFDG were significantly higher in estrogen-receptor negative tumors (p = 0.0300 and 0.0247, respectively). Ki was significantly higher in node-positive than in node-negative disease (p = 0.0315). None of the assessed FDG-kinetic parameters showed significant correlation with stromal TIL. In conclusion, we confirmed a significant relationship between kinetic parameters measured by dynamic PET and the routinely assessed clinicopathological factors of breast cancer: high-grade, hormone-receptor negative tumors with high proliferation rate are characterized by higher cellular FDG-uptake and FDG-phosphorylation rate. Furthermore, we found that kinetic parameters based on the dynamic examinations are probably not influenced by stromal TIL infiltration.

Comparison of different motion correction techniques for dynamic FDG-PET/CT studies in breast cancer patients.

BACKGROUND: Our aim was to evaluate interchangeability of different motion correction methods in the assessment of dynamic FDG-PET/CT studies in breast cancer patients as well as to assess the interrater reliability of these methods. METHODS: In our prospective study we included patients with malignant breast tumours. Dynamic PET acquisition lasted for 60 minutes after tracer (FDG) injection. Every study was assessed by the same two experienced observers. We assessed plasma activity noninvasively. In case of the primary tumour VOIs we applied two different approaches to correct motion artefacts: method I) frame-by-frame manual motion correction; method II) frame-by-frame semi-automatic software-based motion correction. FDG two-compartment kinetic modelling was applied to assess K1, k2, k3 rate coefficients and to calculate Ki (tracer flux constant) and MRFDG (FDG metabolic rate). RESULTS: Thirty-five lesions detected during 34 dynamic studies were included in this current analysis. Interrater reliability of both applied motion correction methods proved to be excellent (ICC=0.89-0.99), except Ki measured by method I (ICC=0.66). Bland-Altman analysis revealed that method II resulted in significantly lower values than method I regarding k3 and Ki in case of both observers, and regarding MRFDG in one of the observers. In case of K1 and k2 the two methods were in good agreement. CONCLUSIONS: Both applied methods proved to be reproducible and reliable, especially method II, where every measured kinetic parameter showed excellent interrater reliability. Different approaches of motion correction could have a significant effect on the results of the kinetic modelling; therefore careful selection of the most reliable method is advised.

[The role of positron emission tomography (PET) in tumor diagnostics and therapy monitoring]. / A pozitron emissziós tomográfia (PET) helye a tumordiagnosztikában és a terápia követésében.

Positron emission tomography (PET) is a medical imaging method belonging to the realm of nuclear medicine. It has been a clinical research tool since the sixties but during the late nineties it became widely utilized in clinical practice too. PET technique requires special radioactive isotopes, which may be generated only in particle accelerators (cyclotrons) and their transport is limited owing to the short physical half-life. PET/CT was born from the combination of PET and CT (computer tomography). The first combined PET/CT scanner began to operate in 1998 and the method has been used in clinical practice since 2001. It is a hybrid (multi-modality) medical imaging equipment which can provide anatomical, morphologic (CT) and functional, metabolic information (PET) simultaneously. PET/CT imaging has gained clinical acceptance mainly in oncology - owing to the attributes of the most frequently used PET tracer, fluoro-deoxy glucose (FDG) - and in a lesser extent in neuropsychiatry and cardiology. The authors in this paper review the basics and key indications of the method, the wider used radiofarmacons, including potential neurological and psychiatric applications, and the possible causes of false positivity and false negativity.

Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

OBJECTIVES: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. METHODS: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. RESULTS: A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p < 0.001) and tumor size (p < 0.001) regarding the primary breast lesions. To predict pCR, Method 2 had higher sensitivity (72.4 % vs. 44.8 %) and negative predictive value (57.9 % vs. 45.8 %) with lower false negativity rate (16 vs. 32) than Method 1. pCR rate was higher in Her2-positive and triple negative tumors. Despite the significant differences detected between the biological subtypes regarding changes in primary tumor SUVmax (p = 0.007) and size (p = 0.015), the subtypes only had significant impact on response evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. CONCLUSIONS: Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.

Response evaluation after primary systemic therapy of Her2 positive breast cancer ­ an observational cross-sectional study.

AIM: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. METHODS: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). CONCLUSION: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

Correlation of the value of 18F-FDG uptake, described by SUVmax, SUVavg, metabolic tumour volume and total lesion glycolysis, to clinicopathological prognostic factors and biological subtypes in breast cancer.

OBJECTIVE: The aim of this study was to observe the relationships between different metabolic parameters and clinicopathological features (CPFs) or immunohistochemically defined biological subtypes (IHC-BS) in breast cancer. MATERIALS AND METHODS: Eighty-two women (83 lesions, tumour size>15 mm) underwent PET/computed tomography imaging after a core biopsy. Maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) in the primary tumour were calculated and compared with CPFs and IHC-BS. Tumours with oestrogen receptor (ER) positivity were separately investigated in relation to their progesterone receptor (PR) status. RESULTS: Significant correlation was found between all metabolic parameters and high nuclear grade or ER status or IHC-BS. All parameters were higher in PR(-) and triple-negative cases than in PR(+) and non-triple-negative tumours, and the correlation was significant for most of the metabolic parameters (except for SUVavg in the case of PR status and MTV in the case of triple negativity). Significant correlation was found only for SUVmax regarding the human epidermal growth factor receptor 2 (HER2) status. There was moderate correlation between the Ki67 expression and the SUVmax or SUVavg. All metabolic parameters were higher in ER(+)/PR(-)/HER2(-) lesions compared with ER(+)/PR(+)/HER2(-) cancers. However, ER(+)/PR(-)/HER2(+) tumours had lower SUVmax and SUVavg compared with ER(+)/PR(+)/HER2(+) lesions. CONCLUSION: Our study confirms that the fluorine-18 fluorodeoxyglucose uptake in primary tumour is associated with distinct CPFs or IHC-BS in breast cancer. SUVmax may reflect tumour metabolism more reliably compared with SUVavg, MTV or total lesion glycolysis. Our preliminary results suggest different biological properties in ER(+) tumours with different PR statuses.

[Is ceCT necessary beyond FDG-PET/CT for primary staging in Hodgkin lymphoma?]. / Szükséges-e Hodgkin-limfóma primer stádium-megállapításához FDG-PET/CT mellett iv. ka. CT elvégzése is?

INTRODUCTION: Several study supported that 18F-Fluoro-deoxy-glucose (FDG) positron emission tomography/computer tomography with low dose CT (standard PET/CT) is more accurate than contrast-enhanced CT (ceCT) in the primary staging of Hodgkin disease. AIM: The authors compared the accuracy of these examinations with this indication in their practice, and analysed the added value of ceCT which was performed as a supplement to standard PET/CT. METHOD: Twenty-eight patients were categorized based on ceCT, single standard PET/CT and standard PET/CT with ceCT. RESULTS: Twenty-four patients were in the same disease-stage based on all methods. Disease was upstaged by standard PET/CT compared to ceCT in 4 patients. There was no change in stage when comparing standard PET/CT and standard PET/CT with ceCT. CONCLUSIONS: Standard PET/CT is more accurate than ceCT in the primary staging of Hodgkin disease. The authors established that it is not reasonable to supplement standard PET/CT with ceCT in this indication.

Value of FDG-PET/CT examinations in different cancers of children, focusing on lymphomas.

The aim of the study was to assess sensitivity and specificity of FDG-PET/CT in different forms of childhood cancer. We retrospectively evaluated the results dedicated of 162 FDG-PET/CT examinations of 86 children treated with: Hodgkin lymphoma (HL; n = 31), non-Hodgkin lymphoma (NHL; n = 30) and other high grade solid tumors (n = 25). Patients were admitted and treated in two departments of pediatric hematology and oncology in Hungary. FDG-PET/CT was performed for staging (n = 25) and for posttreatment evaluation (n = 137). Imaging was performed in three FDG-PET/CT Laboratories, using dedicated PET/CT scanners. False positive results were defined as resolution or absence of disease progression over at least 1 year on FDG-PET/CT scans without any intervention. In some cases histopathological evaluation of suspicious lesions was performed. Fals negative results were defined as negative FDG-PET/CT results in case of active malignancy. Positive predictive values (PPV) and negative predictive values (NPV) were calculated. NPV was 100%. The highest PPV was observed in high grade solid tumors (81%), followed by HL (65%) and NHL (61%). There was a major difference of PPV in different histological types of HL (50% in HL of mixed-cellularity subtype, 90% in nodular sclerosing, and 100% in lymphocyte-rich and lymphocyte depleted HL). We treated one patient with nodular lymphocyte predominant HL, who had 5 false positive FDG-PET/CT results. PPV of T- and B-lineage NHL were similar (60% and 62%, respectively). We observed an interesting difference of PPV in different stages of HL and NHL. In HL PPV was higher in early than in advanced disease forms: 66% in stage II HL and 60% in stage III HL, whereas there was an inverse relationship between PPV and disease stages in NHL 0% in stage I and II patients, 67% in stage III and 100% in stage IV patients. PPV was lower in males (54%) than in females (65%). PPV were 64% vs. 58% in patients under vs. over 10 years of age. Negative FDG-PET/CT results during follow-up reliably predict the absence of malignancy. Positive FDG-PET/CT scan results in general have a low PPV. The relatively high PPV in patients with histologically proven high grade solid tumors, advanced stages of NHL and with nodular sclerosing, lymphocyte-rich and lymphocyte depleted subtypes of HL warrant a confirmation by biopsy, whereas the watch-and-wait approach can be used in other forms of childhood cancer patients with a positive FDG-PET/CT result in course of follow-up examinations.

Port-site metastasis after laparoscopic removal of an isolated adrenal metastasis in a patient with breast cancer detected with FDG PET/CT.

Adrenal metastasis from breast cancer rarely occurs in the course of this disease. Laparoscopic surgery has increased in the therapy for malignant tumors because of its lower morbidity and mortality compared with conventional surgical methods. However, complications such as the appearance of a port-site metastasis may also occur. Clinical examination and conventional cross-sectional imaging usually reveal this only at advanced stage. The authors reported on a case with abdominal wall port-site metastasis detected with F-FDG PET/CT 33 months after the laparoscopic removal of a late-onset, PET/CT-verified adrenal metastasis from lobular breast cancer.

Comparison of the International Harmonization Project, London and Gallamini criteria in the interpretation of 18F-FDG PET/CT examinations after first-line treatment in Hodgkin's lymphoma.

OBJECTIVE: Fluorine 18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has been reported to have a wide-ranging positive predictive value (PPV) in the literary data on Hodgkin's lymphoma after first-line therapy. This study was carried out to compare the usefulness of the International Harmonization Project, London and Gallamini criteria in the interpretation of F-FDG PET/CT examinations for this indication. METHODS: Data from 66 patients with a median follow-up care of 54 months were evaluated. The initial stage had been I-II in the case of 45 patients and III-IV in the case of 21 patients. RESULTS: The analysis based on the International Harmonization Project criteria resulted in a negative predictive value (NPV) of 98.0% and a PPV of 62.5%. Using mediastinal blood pool and liver activity as the thresholds for the London criteria, the NPV and PPV were 98.0 and 62.5% and 98.1 and 71.4%, respectively. Considering only those lesions with F-FDG uptake that was markedly higher than liver uptake as positive, the NPV and PPV were 94.7 and 88.9%, respectively. The analysis based on the Gallamini criteria resulted in an NPV of 96.2% and a PPV of 69.2%. CONCLUSION: Using the London criteria with liver activity as the threshold seems to be a good approach for the interpretation of post-treatment F-FDG PET/CT studies because of its high accuracy and simplicity.