Background: Frontline therapy of Hodgkin lymphoma (HL) is strictly stage-adapted. Staging systems used are based on historical variables which only indirectly reflects tumor load (Ann Arbor stage) or lymphoma cytokine activity (systemic symptoms, erytrocyte sedimentation rate). With new, abbreviated interim PET-tailored chemotherapy schemes (2+2) and reduced radiotherapy protocols, there is a clinical need for precise staging tools. Last years have brought new insight into the prognostic role of metabolic quantitative PET parameters and HL-associated biomarkers. Total metabolic tumor volume (TMTV) measured using fluoro-deoxyglucose PET (FDG-PET) was found to be a predictor of therapy failure after frontline treatment (Kanoun 2014). Interestingly, TMTV was found capable of identifying poor responders within one (intermediate) staging group (Akhtari, 2018; Cottereau 2018). Serum concentrations of thymus and activation-regulated chemokine (TARC) and other cytokines have been proved to have prognostic significance in the patients treated both in the frontline and relapse setting (Moskowitz, 2015; Guidetti 2017). A relationship between pretreatment TMTV, baseline cytokines levels, and current staging systems has not been analyzed yet. Aim: To analyzed quantitative metabolic PET parameters and selected soluble biomarkers in the context of the staging systems used in the U.S. and Europe Methods: We have analyzed a prospectively enrolled cohort of forty-eight patients with HL who were diagnosed in two large university medical centers from 5/2015 to 2/2018. All pts have undergone pretreatment FDG-PET/CT with quantitative analysis of TMTV, Total Lesion Glycolysis (TLG), Maximum Standardized Uptake Volume (SUVmax.) and the Largest Tumor Diameter (LD) and were sampled for cytokine analysis within 16 (median) days from the PET/CT. We have analyzed a set of four serum biomarkers: CD30 (sCD30), CD163 (sCD163), TARC, and interleukin 6 (sIL6), which were measured using ELISA assays. Results: A cohort consisted of 22 males and 26 females with median age of 42 years (range 21-75). Histology subtype was known in all but one case: nodular sclerosis in 23, mixed cellularity 15, lymphocyte-rich in 5 and nodular-lymphocyte predominant (NLPHL) in four. Ann Arbor stages were as follows: I in 5, II in 20, III in 13 and IV in 10 of the pts with systemic symptoms in 20 (42%) of them. All pts were classified according to the German Hodgkin Study Group (GHSG) and NCCN staging systems. GHSG stages - limited, intermediate and advanced were seen in 8 (17%), 10 (21%) and 30 (62%) pts, respectively. NCCN stages were distributed into early favorable in 8 (17%), early unfavorable in 17 (35%) and advanced in 23 (48%) of the pts. Chemotherapy was applied in all but four pts using: BEACOPPesc, combined BEACOPP+ABVD, ABVD and ABV/COPP protocols in 7, 15, 16 and six pts respectively. Of four pts without chemo one case was treated with local radiotherapy and three with WaW (all of them with NLPHL). Treatment response was known in 41 (85%) of the cases with CR, PR, and PD in 33 (80.5%), 6 (14.6%) and two (4.9%) pts, respectively. Relationships between disease stages and PET-parameters are summarized in Table 1. Briefly, metabolic tumor burden (TMTV, TLG) identified two markedly different groups: low and intermediate/high risk. Similarly, cytokines levels were significantly lower in low-risk patients compared to those with intermediate-high risk (Table 2). Treatment outcome did not correlate either with GHSG nor NCCN stage. We found correlation of sIL-6 (p=0.03) but not sCD30 (p=0.09), sCD163 (p=0.14) and TARC (p=0.57) with CR achievement. In terms of PET-parameters the high TMTV>104 cm3 (P=0.046) and TLG>798 (P=0.003) were associated with not achieving of CR with NPV, PPV and test accuracy of 94.4, 22.0, 58.5 for TMTV and 100%, 36,4%, 66% for TLG, respectively. Conclusion: Adequate frontline treatment policy is vital for achieving an optimal balance between efficacy and toxicity. Current staging systems have a weak correlation with metabolic tumor burden: one-third of those recognized as advanced stage have the low burden, and vice versa about a half of intermediate-risk pts have high tumor burden. Combination of TMTV/TLG and cytokines can be currently used for decision making in borderline stage cases and probably could serve as a backbone for a new staging system in the future. Acknowledgment: IGA_LF_2018_004, MH CZ-DRO (FNOL, 00098892) Disclosures No relevant conflicts of interest to declare.
Introduction: Preoperative parathyroid imaging is inevitable part of focused parathyroid surgery. The aim of our study was assessment of parathyroid scintigraphy diagnostic accuracy regarding to size and metabolic parameters of hyperfunctioning parathyroid tissue. Material and methods: Parathyroid scintigraphy for suspected primary hyperparathyroidism was performed in 95 patients during years 2015 and 2016. Of them, 75 patients with known clinical outcome (40 underwent surgery, 35 had documented laboratory follow-up) were further retrospectively evaluated. The performance of dual tracer 99mTc-pertechnetate and 99mTc-MIBI subtraction and dual-time-point 99mTc-MIBI imaging with SPECT/CT was analysed. Serum parathyroid hormone (PTH), calcaemia, ionized calcaemia and phosphataemia and ultrasound detected adenoma volume and largest diameter in false negative and true positive findings were compared using Mann-Whitney test. Results: Sensitivity and specificity of parathyroid scintigraphy was 74.5% and 95.8%, respectively. NPV was 63.8% and PPV 97.4%. Hyperfunctioning parathyroid tissue detectability was almost significantly associated with hypophosphataemia and PTH levels. Conclusion: Parathyroid scintigraphy provides high sensitivity and superior specificity in parathyroid adenoma location, nevertheless the diagnostic accuracy tends to decline in smaller adenomas and in less metabolically active parathyroid tissue causing only subtle biochemical changes. 18F-Fluorocholine PET/CT or 3D SPECT/CT subtraction should be a reasonable option for those cases.
SummaryRadioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient’s upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria.Learning points131I is a combined beta–gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging.RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging.RAI should be considered also in “low-risk” patients, especially when the lymph node involvement is not reliably documented.Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.
Aim. Radioiodine (RAI) improves survival in patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC). Although there has been an ongoing debate on RAI-induced salivary gland damage, published data have been inconsistent. Therefore, the purpose of our study was to compare salivary gland function in intermediate and high risk DTC patients after single or repeated RAI treatment with their age-and sex-matched RAI-naive counterparts. Methods. Uptake and excretion of parotid and submandibular glands were quantitatively evaluated using 99m Tc-pertechnetate salivary gland scintigraphy in 23 patients previously treated with RAI. Patients (median 9.25 GBq 131 I-NaI; Q1-Q3: 5.55-16.65; range: 5.55-27.5) were divided into subgroups according to previously administered 131 I-NaI activity using cut-off values 5.55 GBq and 9.25 GBq. Their salivary gland scintigraphy results were compared with RAI-naive patients using Mann-Whitney test. Results. Compared to RAI-naive patients, parotid glands pertechnetate uptake was significantly lower in those treated with > 9.25 GBq (P=0.034) and parotid glands excretion fraction was already decreased with RAI activities > 5.55 GBq (P=0.031). In submandibular glands, no statistically significant difference in either function was observed even with RAI activity > 9.25 GBq. Conclusion. Our data suggest that RAI therapy using activities ≤ 5.55 GBq does not substantially decrease saliva production. Activities > 5.55 GBq may lead to significant decrease in parotid excretion, and activities > 9.25 GBq also diminish parotid uptake. Surprisingly, submandibular glands, providing majority of seromucinous saliva under basal condition, seem to be unaffected even by RAI activities above 9.25 GBq.
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