Peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy

Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called "remainder of the body" to the bone marrow

Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

Purpose: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Methods: Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. Results: In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 ± 16 to 25 ± 4 ng/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA1clevels (> 6.5%). Conclusion: In men177Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA1c. Therefore, PRRT with177Lu-octreotate can be regarded as a safe treatment modality with respect to short-and long-term endocrine function

Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer:DCCSS-LATER 2 psycho-oncology study

Objective: To describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes. Methods: Siblings of survivors (diagnosed &lt;18 years old, between 1963 and 2001, &gt;5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests. Associations of siblings' sociodemographic and CCS’ cancer-related characteristics with the outcomes were assessed with mixed model analysis. Results: Five hundred five siblings (response rate 34%, 64% female, mean age 37.5, mean time since diagnosis 29.5) of 412 CCS participated. Siblings had comparable HRQoL, anxiety and self-esteem to references with no or small differences (r = 0.08−0.15, p &lt; 0.05) and less depression. Proportions of symptomatic PTSD were very small (0.4%−0.6%). Effect sizes of associations of siblings' sociodemographic and CCS cancer-related characteristics were mostly small to medium (β = 0.19−0.67, p &lt; 0.05) and no clear trend was found in the studied associated factors for worse outcomes. Conclusions: On the very long-term, siblings do not have impaired psychosocial functioning compared to references. Cancer-related factors seem not to impact siblings' psychosocial functioning. Early support and education remain essential to prevent long-term consequences.</p

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Nuclear Medicine Imaging of Neuroendocrine Tumors

An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy (PRRT). In the past decade, different positron-emitting tomography (PET) tracers have been developed. The largest group is the 68 Gallium-labeled somatostatin analogs (Ga-68-SSA). Several studies have demonstrated their superiority compared to SRS in sensitivity and specificity. Furthermore, patient comfort and effective dose are favorable for Ga-68-SSA. Other PET targets like (F-18-[C-11]-5-hydroxy- L-tryptophan (C-11-5-HTP) and 6-F-18-L-3,4-dihydroxyphenylalanine (F-18-DOPA) were developed recently. For insulinomas, glucagon-like peptide-1 receptor imaging is a promising new technique. The evaluation of response after PRRT and other therapies is a challenge. Currently, the official follow-up is performed with radiological imaging techniques. The role of nuclear medicine may increase with the newest tracers for PET. In this review, the different nuclear imaging techniques and tracers for the imaging of NETs will be discussed. (C) 2015 S. Karger AG, Base

Nuclear Medicine Imaging of Neuroendocrine Tumors

An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy (PRRT). In the past decade, different positron-emitting tomography (PET) tracers have been developed. The largest group is the 68 Gallium-labeled somatostatin analogs (Ga-68-SSA). Several studies have demonstrated their superiority compared to SRS in sensitivity and specificity. Furthermore, patient comfort and effective dose are favorable for Ga-68-SSA. Other PET targets like (F-18-[C-11]-5-hydroxy- L-tryptophan (C-11-5-HTP) and 6-F-18-L-3,4-dihydroxyphenylalanine (F-18-DOPA) were developed recently. For insulinomas, glucagon-like peptide-1 receptor imaging is a promising new technique. The evaluation of response after PRRT and other therapies is a challenge. Currently, the official follow-up is performed with radiological imaging techniques. The role of nuclear medicine may increase with the newest tracers for PET. In this review, the different nuclear imaging techniques and tracers for the imaging of NETs will be discussed. (C) 2015 S. Karger AG, Base

Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

Non-functional pancreatic neuroendocrine tumours (NETs) can present with advanced local or distant (metastatic) disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT) using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate) for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET

The metabolic syndrome in a memory clinic population : Relation with clinical profile and prognosis

Background The metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors that is associated with an increased risk of cognitive impairment and dementia. It is unclear however, if the presence of the MetS is associated with a particular clinical profile or a different prognosis in patients with cognitive complaints or early dementia. Objectives  To compare 1) the clinical profile and 2) the prognosis of patients attending a memory clinic according to the presence or absence of MetS. Design Longitudinal cohort. Setting Memory clinic. Participants We included and followed 86 consecutive patients (average age of 66.7 (SD 9.7)) from the Amsterdam Dementia Cohort with an MMSE > 22.  Measurements Clinical profile (neuropsychological examination, brain MRI, cerebrospinal fluid (CSF) biomarkers, clinical diagnosis) on an initial standardized diagnostic assessment was compared according to MetS status. Progression to dementia was assessed in initially nondemented patients (subjective complaints n = 40, mild cognitive impairment n = 24, follow-up available in 59).  Results 35 (41%) patients met the MetS criteria. Demographics were similar between patients with or without the MetS. At baseline, diagnosis, cognitive performance, severity of degenerative or vascular abnormalities on MRI, and CSF amyloid and tau levels did not differ between the groups (all p > 0.05). Among nondemented patients, however, MetS was associated with worse performance on executive function, attention & speed and visuoconstructive ability (z-scores, p < 0.05). During a mean follow-up of 3.4 years a similar proportion of patients with (4; 17%) and without (6; 17%) the MetS progressed to dementia (p = 0.45). Conclusion Among nondemented patients presenting at a memory clinic MetS was associated with slightly worse cognitive performance (worse on tasks assessing executive functions, visuo-constructive ability, attention & speed), but conversion rate to dementia was not increased