Whole-body iodine-131 metaiodobenzylguanidine imaging for detection of bone metastases in patients with paraganglioma: comparison with bone scintigraphy

Iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) therapy is an effective treatment for patients with malignant paraganglioma for which surgical resection is not indicated. We performed high-dose ¹³¹I-MIBG therapy on two patients with malignant paraganglioma and multiple bone metastases. The bone metastases were diagnosed by magnetic resonance imaging (MRI). Metastatic bone lesions were evaluated by whole-body ¹³¹I-MIBG imaging and bone scintigraphy. Whole-body ¹³¹I-MIBG imaging showed extensive metastatic bone lesions, whereas conventional bone scintigraphy did not. There was a remarkable discrepancy between ¹³¹I-MIBG imaging and bone scintigraphy in the diagnosis of metastatic bone lesions of malignant paraganglioma in our two patients. High-dose ¹³¹I-MIBG imaging may detect early stages of bone metastases, compared with bone scintigraphy, in patients with malignant paraganglioma.     

Radioiodinated MIBG in paraganglioma and pheochromocytoma: previous results and early experiences using no-carrier-added MIBG

The majority of pheochromocytomas and paragangliomas are benign, with malignancy occurring in approximately 10% of pheochromocytoma patients. The malignancy rate among paragangliomas is 15–35% or higher if associated with succinate dehydrogenase B gene mutations. The 5-year mortality rate in malignant pheochromocytoma and paraganglioma is nearly 50%. Malignancy of both pheochromocytoma and paraganglioma is determined by the existence of metastasis or local invasion and not by the cellular characteristics. There are no known clinical, biochemical or histopathological differences between pheochromocytoma and paraganglioma.Metaiodobenzylguanidine (MIBG) radiolabeled with either ¹²³I or ¹³¹I has been used to diagnose neuroendocrine tumors such as paraganglioma and pheochromocytoma, and ¹³¹I-MIBG has been used to treat these tumors. The role of radioiodinated MIBG in treating neuroendocrine tumors is still being evaluated. More recently, no-carrier-added (nca) MIBG has become available, and the advantages of nca MIBG over ca MIBG are being demonstrated. This article reviews the biology of paragangliomas and pheochromocytomas, the role of MIBG imaging in the diagnosis of these tumors and the role of both ca and nca ¹³¹I-MIBG in the treatment of these tumors. New data on nca ¹³¹I-MIBG in the therapy of these tumors are included.     

Toxicity of upfront 131I-metaiodobenzylguanidine (131I-MIBG) therapy in newly diagnosed neuroblastoma patients: a retrospective analysis

Purpose

In the treatment of patients with high-risk neuroblastoma, different doses of ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) are administered at different time points during treatment. Toxicity, mainly haematological (thrombocytopenia), from ¹³¹I-MIBG therapy is known to occur in extensively chemotherapy pretreated neuroblastoma patients. Up to now, acute toxicity from ¹³¹I-MIBG as initial treatment has never been studied in a large cohort. The aim of this retrospective study was to document acute toxicity related to upfront ¹³¹I-MIBG.

Methods

All neuroblastoma patients (stages 1–4 and 4S) treated upfront with ¹³¹I-MIBG at the Emma Children’s Hospital, Academic Medical Centre (1992 – 2008) were included in this retrospective analysis. The acute toxicity (during therapy) and short-term toxicity (1st month following therapy) of the first two ¹³¹I-MIBG therapies were studied.

Results

Of 66 patients (34 boys, 32 girls; median age 2.2 years, range 0.1 – 9.4 years), 49 had stage 4 disease, 5 stage 4S, 6 stage 3, 1 stage 2 and 5 stage 1. The median first dose was 441 MBq/kg (range 157 – 804 MBq/kg). The median second dose was 328 MBq/kg (range 113 – 727 MBq/kg). The most frequently observed symptoms were nausea and vomiting (21 %, maximum grade II). The main toxicity was grade IV haematological, occurring only in stage 4 patients, after the first and second ¹³¹I-MIBG therapies: anaemia (5 % and 4 %, respectively), leucocytopenia (3 % and 4 %) and thrombocytopenia (2 % and 4 %). No stem cell rescue was needed.

Conclusion

The main acute toxicity observed was haematological followed by nausea and vomiting. One patient developed posterior reversible encephalopathy syndrome during ¹³¹I-MIBG therapy, possibly related to ¹³¹I-MIBG. We consider ¹³¹I-MIBG therapy to be a safe treatment modality.     

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

Purpose

To evaluate the diagnostic performance of ⁶⁸Ga-DOTATATE ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT), ¹⁸F-FDG PET/CT and ¹³¹I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Materials and Methods

Seventeen patients (male = 8, female = 9; age range, 13–68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent ⁶⁸Ga-DOTATATE and ¹³¹I-MIBG without ¹⁸F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar’s test.

Results

On a per-patient basis, 14/17 patients were detected in ⁶⁸Ga-DOTATATE, 7/17 patients in ¹³¹I-MIBG, and 10/12 patients in ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by ⁶⁸Ga-DOTATATE, 74/472 by ¹³¹I-MIBG, and 154/300 (patient, n = 12) by ¹⁸F-FDG. The sensitivity and accuracy of ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on ⁶⁸Ga-DOTATATE, ¹³¹I-MIBG and ¹⁸F-FDG.

Conclusions

Ga-DOTATATE PET/CT shows high diagnostic accuracy than ¹³¹I-MIBG scintigraphy and ¹⁸F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.     

Diagnostic accuracy of 68Ga-DOTANOC PET/CT imaging in pheochromocytoma

Purpose

The purpose of the present study was to evaluate the diagnostic accuracy of ⁶⁸Ga-DOTANOC positron emission tomography (PET)/CT in patients with suspicion of pheochromocytoma.

Methods

Data of 62 patients [age 34.3?±?16.1 years, 14 with multiple endocrine neoplasia type 2 (MEN2)] with clinical/biochemical suspicion of pheochromocytoma and suspicious adrenal lesion on contrast CT (n?=?70), who had undergone ⁶⁸Ga-DOTANOC PET/CT, were retrospectively analyzed. PET/CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUV_max), SUV_mean, SUV_max/SUV_liver, and SUV_mean/SUV_liver. Results of PET/CT were compared with ¹³¹I-metaiodobenzylguanidine (MIBG) imaging, which was available in 40 patients (45 lesions). Histopathology and/or imaging/clinical/biochemical follow-up (minimum 6 months) was used as reference standard.

Results

The sensitivity, specificity, and accuracy of ⁶⁸Ga-DOTANOC PET/CT was 90.4, 85, and 88.7 %, respectively, on patient-based analysis and 92, 85, and 90 %, respectively, on lesion-based analysis. ⁶⁸Ga-DOTANOC PET/CT showed 100 % accuracy in patients with MEN2 syndrome and malignant pheochromocytoma. On direct comparison, lesion-based accuracy of ⁶⁸Ga-DOTANOC PET/CT for pheochromocytoma was significantly higher than ¹³¹I-MIBG imaging (91.1 vs 66.6 %, p?=?0.035). SUV_max was higher for pheochromocytomas than other adrenal lesions (p?=?0.005), MEN2-associated vs sporadic pheochromocytoma (p?=?0.012), but no difference was seen between benign vs malignant pheochromocytoma (p?=?0.269).

Conclusion

⁶⁸Ga-DOTANOC PET/CT shows high diagnostic accuracy in patients with suspicion of pheochromocytoma and is superior to ¹³¹I-MIBG imaging for this purpose. Best results of ⁶⁸Ga-DOTANOC PET/CT are seen in patients with MEN2-associated and malignant pheochromocytoma.     

Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients

Objective

To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA).

Materials and Methods

Seventy-nine consecutive patients (54.5 ± 11.2 years old) with 114 breast cancer metastases (28.9 ± 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates.

Results

The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13–4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22–4.82]; p = 0.011, respectively).

Conclusion

PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome.

     

Partial Nephrectomy versus Thermal Ablation for Clinical Stage T1 Renal Masses: Systematic Review and Meta-Analysis of More than 3,900 Patients

Purpose

A systematic review and meta-analysis of clinical trials was undertaken to compare percutaneous thermal ablation versus partial nephrectomy (PN) for stage T1 renal tumors.

The role of 131I-metaiodobenzylguanidine (MIBG) therapy in unresectable and compromising localised neuroblastoma

Purpose

In patients with localised neuroblastoma without adverse genetic aberrations, observational treatment is justified. Therapy is required when organ or respiratory functions have become compromised. As the outcome is good, side effects of treatment should be prevented. The aim of this retrospective study was to evaluate response and outcome in patients treated with ¹³¹I-metaiodobenzylguanidine (MIBG) for unresectable localised neuroblastoma, with compromised organ functions.

Methods

Patients with localised neuroblastoma [median age 1.6 years (0–5.5 years)] diagnosed between 1989 and 2008 were included in this retrospective study (n?=?21). Primary tumours were unresectable and there was a compromised organ or respiratory function. Diagnosis and staging were performed according to the International Neuroblastoma Staging System. Fixed doses of ¹³¹I-MIBG therapy (50–200 mCi) were given. The median number of infusions was two (range one to seven). Response was graded according to the International Neuroblastoma Response Criteria.

Results

Of the 21 patients, 14 did not need any chemotherapy. Patients were treated with ¹³¹I-MIBG therapy and, in most cases, with additional surgery and/or chemotherapy. Sixteen achieved complete response (CR), three very good partial response (VGPR), one partial response (PR) and one progressive disease (PD). Two patients died of PD after having achieved CR initially and due to surgical complications a few months after resection. Ten-year overall survival and event-free survival were 90.5 %. The median follow-up was 8.5 years (range 0.4–19.6 years).

Conclusion

¹³¹I-MIBG therapy is an effective treatment modality for unresectable localised neuroblastoma with compromised organ functions. However, this was a small and heterogeneous cohort and further studies are needed.     

Combination of 123I-metaiodobenzylguanidine scintigraphy and flow-mediated dilation for the detection of patients with coronary spastic angina

Background

This study evaluated the usefulness of cardiac sympathetic nerve activity, estimated by ¹²³I-MIBG scintigraphy, and endothelial function, estimated by flow-mediated dilation (FMD), in the detection of coronary spastic angina (CSA).

Methods and results

We compared 78 consecutive patients suspected of CSA with ten age-matched controls. On the basis of a spasm provocation test with acetylcholine, 53 patients were diagnosed as CSA and 25 patients were considered to have chest-pain syndrome (CPS). The total defect score (TDS) by delayed ¹²³I-MIBG scintigraphy was significantly higher in both patient groups than in controls (P < 0.05), and was significantly higher in CSA than in CPS patients (P = 0.02). The heart/mediastinum activity (H/M) ratio by delayed ¹²³I-MIBG scintigraphy and FMD were significantly lower in both patient groups than in controls (P < 0.05), and were lower in CSA than in CPS patients (P = 0.04). In receiver-operating curve analysis, the areas under the curve for TDS, H/M, and FMD were 0.78, 0.72, and 0.70, respectively. The combination of delayed ¹²³I-MIBG scintigraphy and FMD showed a higher diagnostic value than either method alone.

Conclusions

¹²³I-MIBG scintigraphy and FMD can distinguish CSA patients among patients complaining of chest pain at rest, with good sensitivity and specificity.     

Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction

Objective

Iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) has been used to assess the function of the cardiac sympathetic nervous system in patients with chronic heart failure (HF). The usefulness of ¹²³I-MIBG imaging for evaluating patients with heart failure with preserved ejection fraction (HFPEF) has not been established.

Methods

We performed ¹²³I-MIBG scintigraphy and echocardiography and measured the plasma brain natriuretic peptide (BNP) levels of 117 consecutive HF patients (64 men, mean age 66 ± 14 years) with a left ventricular ejection fraction (LVEF) of ≥50% who were admitted to our hospital. Patients were divided into 2 groups according to the New York Heart Association (NYHA) functional class.

Results

The ¹²³I-MIBG delayed heart-to-mediastinum (H/M) ratio was significantly lower, and the washout rate (WR) was higher in patients with HFPEF with advanced NYHA functional class (NYHA functional class I and II vs. III: 1.90 ± 0.34 vs. 1.49 ± 0.32, p < 0.0001; 25.9 ± 13.4 vs. 46.9 ± 16.3%, p < 0.0001, respectively). On the other hand, the ¹²³I-MIBG WR was not correlated with LVEF and had a weak correlation with plasma BNP levels (R = 0.207, p = 0.0346). Moreover, patients with a high ¹²³I-MIBG WR showed a poor clinical outcome (p = 0.0033).

Conclusions

¹²³I-MIBG imaging provides independent prognostic information in patients with HFPEF.     

Discrepant uptake of the radiolabeled norepinephrine analogues hydroxyephedrine (HED) and metaiodobenzylguanidine (MIBG) in rat hearts

Purpose

¹¹C-Hydroxyephedrine (HED) and radioiodinated metaiodobenzylguanidine (¹²³I/¹³¹I-MIBG) are catecholamine analogue tracers for sympathetic nerve positron emission tomography/single photon emission computed tomography (PET/SPECT) imaging. In contrast to humans, rat hearts demonstrate high nonneural catecholamine uptake-2 in addition to neural uptake-1, the contributions of which to tracer accumulation are not fully elucidated.

Methods

Wistar rats were studied using the following pretreatments: uptake-1 blockade with desipramine 2 mg/kg IV, both uptake-1 and -2 blockade with phenoxybenzamine 50 mg/kg IV, or control with saline IV. HED or ¹²³I-MIBG was injected 10 min after pretreatment, and rats were sacrificed 10 min later. Heart to blood tissue count ratio (H/B ratio) was obtained using a gamma counter. To determine regional tracer uptake, dual-tracer autoradiography was performed with HED and ¹³¹I-MIBG in Wistar rats with chronic infarction by transient coronary occlusion and reperfusion and in healthy control rats. Local tracer distributions were analyzed, and the infarcted rats’ local tracer distributions were compared with histology.

Results

The H/B ratios in control hearts were 34.4?±?1.7 and 25.5?±?2.1 for HED and ¹²³I-MIBG, respectively. Desipramine led to a significant decrease in HED (3.2?±?0.5, p?<?0.0001), while there was no change in ¹²³I-MIBG (25.5?±?6.4, p?=?n.s.). Phenoxybenzamine led to a significant decrease in both HED and ¹²³I-MIBG (3.5?±?0.02, 4.3?±?0.7, p?<?0.0001). Only HED showed a subepicardium-subendocardium gradient in healthy control hearts which is consistent with physiological innervation, while ¹³¹I-MIBG was evenly distributed throughout the myocardium. ¹³¹I-MIBG uptake defect closely matched the scar area determined by histology [3.8?±?2.3 % (¹³¹I-MIBG defect) vs 4.0?±?2.4 % (scar)]. However, the scar area was clearly exceeded by the HED uptake defect (9.1?±?2.2 %, p?<?0.001).

Conclusion

HED uptake showed high specificity to neural uptake-1 in rat hearts. On the other hand, ¹²³I/¹³¹I-MIBG demonstrated distinct characters of regional tracer distribution and uptake mechanism that are compatible with significant contribution of nonneural uptake-2.     

Iodine-123 metaiodobenzylguanidine imaging can predict future cardiac events in Japanese patients with Parkinson’s disease

Objectives

Iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) myocardial scintigraphy provides useful diagnostic information in differentiating Parkinson’s disease (PD) from other neurological diseases. Moreover, a number of studies have reported that ¹²³I-MIBG imaging provides powerful diagnostic and prognostic information in congestive heart failure (HF) patients. The aim of the present study was to investigate the cardiovascular predictive value of cardiac ¹²³I-MIBG imaging in patients with PD.

Methods

Seventy-eight patients with PD were retrospectively studied. All patients underwent ¹²³I-MIBG imaging at 30 min (early) and 240 min (delayed) after the tracer injection, and clinical parameters were also investigated.

Results

During a mean follow-up of 27 ± 12 months, 5 patients required hospitalization for HF. There were no occurrences of myocardial infarction, fatal arrhythmia or sudden death. There was no significant coronary artery stenosis, significant valvular heart disease, or cardiomyopathy in the HF patients. The left ventricular ejection fraction (LVEF) was normal in the HF patients. ¹²³I-MIBG delayed heart to mediastinal ratio (delayed H/M) was lower and washout rate (WR) was higher in HF patients than non-HF patients (1.62 ± 0.21 vs. 1.34 ± 0.08, p = 0.019; 31.9 ± 5.5 vs. 38.2 ± 3.3, p = 0.005, respectively). Both WR and delayed H/M did not correlate with Hoehn and Yahr stage. The WR showed a weak negative correlation with delayed H/M (R = ?0.357, p < 0.001) upon simple linear regression analysis. A multivariate Cox regression analysis revealed that WR and delayed H/M were independently associated with HF (p = 0.014, p = 0.029, respectively). Kaplan–Meier analysis revealed that patients with abnormal WR (>37 %) and delayed H/M (<1.48) had a higher incidence of HF than those with normal WR and delayed H/M (p = 0.014, p = 0.04, respectively).

Conclusions

WR showed stronger predictive power than delayed H/M in Kaplan–Meier analysis. WR has more useful cardiovascular predictive value than delayed H/M in Japanese patients with PD. Further studies are needed to clarify the significance of abnormal MIBG uptake in PD patients.     

Antitumor effects of radionuclide treatment using α-emitting <Emphasis Type="Italic">meta</Emphasis>-<Superscript>211</Superscript>At-astato-benzylguanidine in a PC12 pheochromocytoma model

Purpose

Therapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-¹³¹I-iodo-benzylguanidine (¹³¹I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-²¹¹At-astato-benzylguanidine (²¹¹At-MABG) are expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in an animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of the α-emitter ²¹¹At-MABG in a pheochromocytoma model.

Methods

We evaluated tumor volume-reducing effects of ²¹¹At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of ²¹¹At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group). Tumor volumes were evaluated for 8 weeks after ²¹¹At-MABG administration. The control group of ten mice received phosphate-buffered saline.

Results

The ²¹¹At-MABG-treated mice showed significantly lower relative tumor growth during the first 38 days than the control mice. The relative tumor volumes on day 21 were 509.2%?±?169.1% in the control mice and 9.6%?±?5.5% in the mice receiving 0.56 MBq (p?<?0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq of ²¹¹At-MABG showed only a temporary weight reduction, with recovery in weight by day 10.

Conclusion

²¹¹At-MABG exhibited a strong tumor volume-reducing effect in a mouse model of pheochromocytoma without weight reduction. Therefore, ²¹¹At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma.

     

<Superscript>18</Superscript>F–fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment

Purpose

Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of ¹⁸F–fluorodeoxyglucose positron emission tomography (¹⁸F–FDG PET) for predicting tumour progression during sorafenib treatment.

Methods

We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing ¹⁸F–FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured.

Results

Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis.

Conclusion

Pretreatment tumour metabolic activity assessed by ¹⁸F–FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment.

     

Prognostic value of pre-operative glucose-corrected maximum standardized uptake value in patients with non-small cell lung cancer after complete surgical resection and 5-year follow-up

Introduction

In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection.

Methods

This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years.

Results

Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman’s ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56–87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3–14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0–9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8–12.9) vs. 6.6 (3.0–8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50–0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51–0.91) for SUVmax (p = 0.75).

Conclusion

Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

     

Prognostic value of <Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomography in patients with gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma

Objective

Gastric neuroendocrine carcinomas (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) are very rare, aggressive tumors of the stomach. We aimed to examine predictive role of pretreatment ¹⁸F-FDG PET/CT-assessed metabolic parameter of primary tumors and metastases in patients with gastric NEC and MANEC.

Methods

We conducted a review of the 27 patients with histopathologically confirmed NECs (n = 10) and MANEC (n = 17) of the stomach at our institution between January 2005 and December 2012. All patients underwent ¹⁸F-FDG-PET examination at diagnosis. Metabolic parameters [SUV_max, SUV_mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] of the primary tumor and metastases on baseline PET/CT were analyzed.

Results

The median follow-up duration was 39.4 months (95 % CI 20.0–58.1 months) and the median overall survival (OS) was 25.7 months (95 % CI 14.1–37.2 months). All gastric lesions were well visualized (average SUV_max = 12.0, range 3.0–41.8). When subjects were divided into two groups by ROC cut-off value of 210.9 and 612, patients with high TLG in primary lesion and metastases showed poorer prognosis compared to low TLG patients (P = 0.09, P = 0.002, respectively). In the sub-analysis of patients with metastasis (n = 12), patients with high TLG in whole body tumor showed significantly shorter OS compared to those with low TLG (31.7 ± 11.4 vs. 7.2 ± 2.1 months, P = 0.006).

Conclusion

¹⁸F-FDG PET/CT is useful in evaluating prognosis of advanced gastric cancer with neuroendocrine carcinoma components. Baseline MTV of primary gastric cancer with metastatic disease, and MTV, TLG of metastases may be prognostic markers in patients with gastric NEC and MANEC.

     

Individualized risk assessment in neuroblastoma: does the tumoral metabolic activity on <Superscript>123</Superscript>I-MIBG SPECT predict the outcome?

Purpose

Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic ¹²³I-MIBG SPECT for individualized image-based prediction of outcome.

Methods

This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3–6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic ¹²³I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell’s C and likelihood ratio χ ².

Results

Median follow-up was 36 months (range 7–107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS.

Conclusions

In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy.

     

Outcome and prognostic factors in single brain metastases from small-cell lung cancer

Purpose

Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1–4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT.

Methods

A total of 52 patients were identified in the authors’ cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS.

Results

The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06–4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11–0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14–4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35–0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15–0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09–4.45; p = 0.028).

Conclusions

Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response to initial chemotherapy appeared to be major prognostic factors. Multivariate analysis revealed metachronous disease as a significantly negative prognostic factor on OS. The value of WBRT, stereotactic radiosurgery (SRS), or surgery alone or in combination for patients with a limited number of BM in SCLC should be evaluated in further prospective clinical trials.

     

Prediction of all-cause mortality from gated-SPECT global myocardial wall thickening

Background

The aim of this study was to assess the correlation between global wall thickening (GWT) obtained by gated-single photon emission computed tomography (SPECT) and echocardiographic measures [ejection fraction (EF), global longitudinal strain (GLS), and strain rate (GLSR)] and to compare their prognostic value for all-cause mortality.

Methods and Results

Seventy-four patients with referral for dipyridamole myocardial perfusion SPECT were prospectively included and underwent transthoracic echocardiography to measure left ventricular EF, GLS, and GLSR. The strongest correlation with GWT was for EF (R = 0.63, P < .001), followed by GLSR (R = ?0.57, P < .001) and GLS (R = ?0.53, P < .001). There were ten deaths over a period of 14.6 ± 5.7 months. Using the multivariate Cox analysis, summed stress score (HR 1.108; P = .023), EF (HR 1.01, P = .031), GLS (HR 1.593, P = .001), and GWT (HR 0.898, P = .034) remained independent predictors of mortality. Mean survival rate evaluated by Kaplan-Meier analysis was longer in patients with GWT ≥ 24% (21.9 ± 0.6 months) than those with GWT < 24% (13.6 ± 2.7 months; P < .001).

Conclusions

GWT assessed is a highly sensitive tool to detect early myocardial systolic dysfunction and may bring additional prognostic information.     

131I-metaiodobenzylguanidine therapy for malignant pheochromocytoma

¹³¹I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1–3 doses of 3.33–4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patient had no symptoms before¹³¹I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 weekto 1 month after¹³¹I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from¹³¹I-MIBG therapy. Thus,¹³¹I-MIBG appears to be useful for the palliation of malignant pheochromocytoma.