Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established. BACKGROUND: A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients' genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model. RESULTS: Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75-0.88) and 0.76 (95% CI: 0.56-0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74-0.87). CONCLUSIONS: We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.

Safety and Efficacy of Peptide-Receptor Radionuclide Therapy in Elderly Neuroendocrine Tumor Patients.

Peptide receptor radionuclide therapy (PRRT) is a well-established treatment in somatostatin receptor-expressing neuroendocrine tumours (NETs). The safety and efficacy of PRRT in >79 years old patients (EP) have not been systematically investigated. All patients with inoperable/metastatic/progressive G1/G2 NET, >79 years (EP), treated with PRRT at the University Hospital of Basel between 2006 and 2018, were enrolled in this retrospective matched cohort study. Each patient was manually matched with ≥1 younger patient (YP = 60-70 years). The primary endpoint was toxicity. Toxicity (subacute, long-term) was graded according to the criteria for adverse events (CTCAE) v5.0. All toxicity grades ≥ 3, or whose delta (Δ) to baseline were ≥2, were considered significant. The odds ratio (OR) for developing toxicity was tested for non-inferiority of EP vs. YP. Clinical response to PRRT and overall survival (OS) were assessed as secondary outcome measures. Forty-eight EP and 68 YP were enrolled. Both cohorts were balanced regarding median time since diagnosis, tumour location, grading, treatment scheme, and baseline biochemical parameters, except for eGFR (EP: 61 ± 16 vs. YP: 78 ± 19; mL/min/1.73 m2). Twenty-two grade ≥ 3 or Δ ≥ 2 subacute hematotoxicities occurred in 10 EP (10.3% of cycles) and 37 in 19 YP (11.6% of cycles; p = NS). Long-term grade ≥ 3 renal toxicity occurred in 7 EP and 2 YP (p = NS). The median OS was 3.4 years (EP) vs. 6.0 years (YP), HR: 1.50 [0.75, 2.98], p = NS. PRRT is a valid therapeutic option in elderly NET patients with similar toxicity and non-inferior survival compared to matched younger patients.

Peptide receptor radionuclide therapy in patients with metastatic progressive pheochromocytoma and paraganglioma: long-term toxicity, efficacy and prognostic biomarker data of phase II clinical trials.

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) have currently only limited treatment options available for patients in the metastatic phase (mPPGL) in either post-surgery or inoperable settings. However, these rare tumors overexpress somatostatin receptors and can thus be treated with peptide receptor radionuclide therapy (PRRT). We present data about our 10-year experience treating 46 consecutive mPPGL patients with 90Y-DOTATOC or 177Lu-DOTATATE. PATIENTS AND METHODS: All patients (20 men and 26 women, median age 52 years) showed positive scintigraphic imaging at 111In-octreotide or 68Ga-DOTATOC positron emission tomography/computed tomography (PET/CT). 90Y-DOTATOC was administered in 12 patients, with cumulative dosages ranging from 7.4 to 11 GBq, while 34 patients received 18.5 or 27.5GBq of 177Lu-DOTATATE. We used Southwest Oncology Group Response Evaluation Criteria in Solid Tumors criteria to evaluate treatment efficacy and Common Terminology Criteria for Adverse Events criteria to assess toxicity. The prognostic role of primary tumor site, hormone secretion, succinate dehydrogenase (SDHx) mutation, and metastatic involvement was also evaluated. RESULTS: Both 90Y-DOTATOC and 177Lu-DOTATATE PRRT were well tolerated by patients without significant renal or bone marrow toxicity. The median follow-up was 73 months (range 5-146 months). The overall disease control rate (DCR) was 80% [95% confidence interval (CI) 68.9% to 91.9%] with a mean five cycles of therapy. However, 177Lu-DOTATATE patients showed a longer median overall survival (mOS) than those receiving 90Y-Dotatoc and a better DCR when higher dosages were administered, even if a direct comparison was not carried out. Syndromic patients had a poorer mOS. SDHx mutations did not interfere with treatment efficacy. CONCLUSIONS: PRRT is safe and effective for the treatment of patients with progressive mPPGL, especially at higher dosages. The longer mOS of 177Lu-DOTATATE-treated patients in our protocols indicates the former radiopharmaceutical as the better candidate for further clinical application.

First Ex Vivo Results of ß--Radioguided Surgery in Small Intestine Neuroendocrine Tumors with 90Y-DOTATOC.

Background: In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with ß--radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, ex vivo specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested. Materials and Methods: SI-NET presents a high uptake of a beta-emitting radiotracer, 90Y-DOTATOC. Five SI-NET patients were enrolled after performing a 68Ga-DOTATOC positron emission tomography/computed tomography (CT) and a CT enterography; 24 h before surgery, they received 5 mCi of 90Y-DOTATOC. Results: Surgery was performed as routine. Tumors and surrounding tissue were sectioned in different samples and examined ex vivo with the beta-detecting probe. All the tumor samples showed high counts of radioactivity that was up to a factor of 18 times higher than the corresponding cutoff value, with a sensitivity of 96% and a specificity of 100%. Conclusions: These first ex vivo RGS tests showed that this probe can discriminate very effectively between tumor and healthy tissues by the administration of low activities of 90Y-DOTATOC, allowing more precise surgery.

Peptide Receptor Radionuclide Therapy Targeting the Somatostatin Receptor: Basic Principles, Clinical Applications and Optimization Strategies.

Peptide receptor radionuclide therapy (PRRT) consists of the administration of a tumor-targeting radiopharmaceutical into the circulation of a patient. The radiopharmaceutical will bind to a specific peptide receptor leading to tumor-specific binding and retention. The only target that is currently used in clinical practice is the somatostatin receptor (SSTR), which is overexpressed on a range of tumor cells, including neuroendocrine tumors and neural-crest derived tumors. Academia played an important role in the development of PRRT, which has led to heterogeneous literature over the last two decades, as no standard radiopharmaceutical or regimen has been available for a long time. This review provides a summary of the treatment efficacy (e.g., response rates and symptom-relief), impact on patient outcome and toxicity profile of PRRT performed with different generations of SSTR-targeting radiopharmaceuticals, including the landmark randomized-controlled trial NETTER-1. In addition, multiple optimization strategies for PRRT are discussed, i.e., the dose-effect concept, dosimetry, combination therapies (i.e., tandem/duo PRRT, chemoPRRT, targeted molecular therapy, somatostatin analogues and radiosensitizers), new radiopharmaceuticals (i.e., SSTR-antagonists, Evans-blue containing vector molecules and alpha-emitters), administration route (intra-arterial versus intravenous) and response prediction via molecular testing or imaging. The evolution and continuous refinement of PRRT resulted in many lessons for the future development of radionuclide therapy aimed at other targets and tumor types.

Inflammation-Based Index and 68Ga-DOTATOC PET-Derived Uptake and Volumetric Parameters Predict Outcome in Neuroendocrine Tumor Patients Treated with 90Y-DOTATOC.

We performed post hoc analyses on the utility of pretherapeutic and early interim 68Ga-DOTATOC PET tumor uptake and volumetric parameters and a recently proposed biomarker, the inflammation-based index (IBI), for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor (NET) patients treated with 90Y-DOTATOC in the setting of a prospective phase II trial. Methods: Forty-three NET patients received up to 4 cycles of 90Y-DOTATOC at 1.85 GBq/m2/cycle with a maximal kidney biologic effective dose of 37 Gy. All patients underwent 68Ga-DOTATOC PET/CT at baseline and 7 wk after the first PRRT cycle. 68Ga-DOTATOC-avid tumor lesions were semiautomatically delineated using a customized SUV threshold-based approach. PRRT response was assessed on CT using RECIST 1.1. Results: Median progression-free survival and overall survival (OS) were 13.9 and 22.3 mo, respectively. An SUVmean higher than 13.7 (75th percentile) was associated with better survival (hazard ratio [HR], 0.45; P = 0.024), whereas a 68Ga-DOTATOC-avid tumor volume higher than 578 cm3 (75th percentile) was associated with worse OS (HR, 2.18; P = 0.037). Elevated baseline IBI was associated with worse OS (HR, 3.90; P = 0.001). Multivariate analysis corroborated independent associations between OS and SUVmean (P = 0.016) and IBI (P = 0.015). No significant correlations with progression-free survival were found. A composite score based on SUVmean and IBI allowed us to further stratify patients into 3 categories with significantly different survival. On early interim PET, a decrease in SUVmean of more than 17% (75th percentile) was associated with worse survival (HR, 2.29; P = 0.024). Conclusion: Normal baseline IBI and high 68Ga-DOTATOC tumor uptake predict better outcome in NET patients treated with 90Y-DOTATOC. This method can be used for treatment personalization. Interim 68Ga-DOTATOC PET does not provide information for treatment personalization.

A five-compartment biokinetic model for 90 Y-DOTATOC therapy.

PURPOSE: Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor-binding peptides such as 90 Y- and 177 Lu-DOTATOC. The objective of this work was to develop a biokinetics model of 90 Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor. METHODS: A multi-compartment model described by two sets of differential equations, one set for the actual 30-min infusion and the other set for the post-infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter-compartment transfer coefficients, λij , were varied to yield the best fit of the calculated to the measured time-activity data and the 90 Y-DOTATOC time-activity data in the five-compartments comprising the human body were thus determined. The resulting time-activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self-dose 90 Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses. RESULTS: Transfer coefficients λij , were determined for five-compartments for all patients. Time- activity curves of 90 Y-DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73-2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05-42.31 mGy/MBq). CONCLUSION: Analytical solution of a biokinetic model for 90 Y-DOTATOC therapy enabled determination of the transfer coefficients and derivation of time-activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.

90Y-DOTATOC Dosimetry-Based Personalized Peptide Receptor Radionuclide Therapy.

Pretherapy PET with 86Y-DOTATOC is considered the ideal dosimetry protocol for 90Y-DOTATOC therapy; however, its cost, limited availability, and need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. The goal of this study was to develop a dosimetric method for 90Y-DOTATOC using 90Y-DOTATOC PET/CT and bremsstrahlung SPECT/CT and to determine whether dosimetry-based administered activities differ significantly from standard administered activities. Methods: This was a prospective phase 2 trial of 90Y-DOTATOC therapy in patients with somatostatin receptor-positive tumors. 90Y-DOTATOC was given in 3 cycles 6-8 wk apart. In the first cycle of therapy, adults received 4.4 GBq and children received 1.85 GBq/m2; the subsequent administered activities were adjusted according to the dosimetry of the preceding cycle so as not to exceed a total kidney dose of 23 Gy and bone marrow dose of 2 Gy. The radiation dose to the kidneys was determined from serial imaging sessions consisting of time-of-flight 90Y-DOTATOC PET/CT at 5 h after therapy and 90Y-DOTATOC bremsstrahlung SPECT/CT at 6, 24, 48, and 72 h. The PET/CT data were used to measure the absolute concentration of 90Y-DOTATOC and to calibrate the bremsstrahlung SPECT kidney clearance data. The radiation dose to the kidneys was determined by multiplying the time-integrated activity (from the fitted biexponential curve of renal clearance of 90Y-DOTATOC) with the energy emitted per decay, divided by the mass of the kidneys. Results: The radiation dose to the kidneys per cycle of 90Y-DOTATOC therapy was highly variable among patients, ranging from 0.32 to 3.0 mGy/MBq. In 17 (85%) of the 20 adult patients who received the second and the third treatment cycles of 90Y-DOTATOC, the administered activity was modified by at least 20% from the starting administered activity. Conclusion: Renal dosimetry of 90Y-DOTATOC is feasible using 90Y-DOTATOC time-of-flight PET/CT and bremsstrahlung SPECT/CT and has a significant impact on the administered activity in treatment cycles.

Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life.

Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a ß-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%-70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided.

Effectiveness of radiolabelled somatostatin analogues (90Y-DOTATOC and 177Lu-DOTATATE) in patients with metastatic neuroendocrine tumours: a single centre experience in Mexico. / Eficacia de los análogos de somatostatina radiomarcados (90Y-DOTATOC y 177Lu-DOTATATE) en pacientes con tumores neuroendocrinos metastásicos, experiencia de centro único en México.

OBJECTIVE: To determine the effectiveness of therapy with the radiolabelled somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, in the treatment of metastatic neuroendocrine tumours with progression to first-line treatment. MATERIAL AND METHODS: A study was conducted on 30 patients diagnosed with neuroendocrine tumours (gastroenteropancreatic, bronchopulmonary, MEN2A, MEN2B, phaeochromocytoma, and paraganglioma) with metastatic disease diagnosed by the pathology department, with progression to first-line treatment, and recruited from December 2014 to February 2016. Efficacy was analysed using computed tomography (CT) according RECIST 1.1 criteria, and the molecular changes using the SUVmax of PET/CT with 68Ga-DOTATOC. Safety was carried out with a renal scan with 99mTc-MAG3. RESULTS: The 30 patients received a total of 49 cycles 90Y-DOTATOC (21 doses) and 177 Lu-DOTATATE (28 doses), with a mean of 1.5 cycles per patient. Of these, 17 (56.7%) showed a partial morphological response, 22 (73.3%) molecular and biochemical response, and 23 (76.6%) clinical response. One patient died during the median follow-up of 13 months. The median overall survival from diagnosis was 54 months (95% CI; 31.18-76.81), and median progression-free survival was 32 months (95% CI; 15.00-48.99). CONCLUSION: Therapy with 90Y-DOTATOC and 177Lu-DOTATATE is a promising therapy for patients with well and moderately differentiated neuroendocrine tumours. The efficacy is better the larger the number of cycles administered, inversely proportional to the number of metastases (<10), and is associated with the level of uptake according to the SUVmax by the metastases, regardless of metabolically active tumour volume.

Feasibility and utility of re-treatment with (177)Lu-DOTATATE in GEP-NENs relapsed after treatment with (90)Y-DOTATOC.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with (177)Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with (90)Y-DOTATOC (Y-PRRT). METHODS: Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. RESULTS: Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6%, median PFS was 22 months (95% CI 16 months - not reached) compared to 28 months (95% CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. CONCLUSION: Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment.

Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors.

Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer (111)In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also (11)C-5-HTP, (18)F-DOPA and (123)I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established.

Yttrium-based therapy for neuroendocrine tumors.

Peptide receptor radionuclide therapy with (90)Y-peptides is generally well tolerated. Acute side effects are usually mild; some are related to the coadministration of amino acids and others to the radiopeptide itself. Chronic and permanent effects on target organs, particularly kidneys and bone marrow, are generally mild if necessary precautions are taken. The potential risk to kidney and red marrow limits the amount of radioactivity that may be administered. However, when tumor masses are irradiated with adequate doses, volume reduction may be observed. (90)Y-octreotide has been the most used radiopeptide in the first 8 to 10 years of experience.

Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC?

PURPOSE: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT). PATIENTS AND METHODS: Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable. RESULTS: According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g. CONCLUSION: Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.

Tratamiento de tumores neuroendocrinos (TNE) con péptidos análogos de la somatostatina marcados con radionucleidos / Treatment of neuroendocrine tumors (NET) with radiolabelled somatostatin analogues

Propósito. Los TNE avanzados tienen escasa respuesta a radioterapia o quimioterapia, el tratamiento sistémico con análogos de la SST radiactivos es una herramienta promisoria en su tratamiento. Presentamos nuestra experiencia, pionera en Latinoamérica, utilizando análogos de SST marcados con 90Y ó 177Lu. Material. Evaluamos 40 pacientes (50.3 años, rango 12-74) con TNE confirmados histológicamente y sobre-expresión de receptores de SST demostrada mediante imágenes. SPECT (111In-DOTATOC) ó PET/CT (68Ga-DOTATATE). Se evaluó respuesta clínica, laboratorio, imágenes con 111In-DOTATATE, post-terapia con 90Y ó 177Lu, 68Ga-DOTATATE PET/CT o TAC. Resultados. Observamos progresión de enfermedad en 10 (25.0 por ciento), remisión parcial en 25 (62.5 por ciento), enfermedad estable en 3 (7.5 por ciento) y remisión completa en 2 (5.0 por ciento). Hubo escasa toxicidad sin deterioro renal significativo. Observamos reducción tumoral y mejoría de calidad de vida en la mayoría de los pacientes. Conclusión. La terapia con radiopéptidos es un procedimento seguro y efectivo en el tratamiento de TNE avanzados.

Purpose. Advanced NETs have little response to radiotherapy or chemotherapy, systemic treatment with radioactive SST analogous is a promissory tool in its treatment. We present our pioneering experience in Latin America using analogous of SST labeled either with 90Y or 177Lu. Materials. We evaluated 40 patients (50.3 years, range 12-74) with histological proved NET and SST receptors over-expression demonstrated by SPECT or PET/CT images with 111In-DOTATOC or 68Ga-DOTATATE. We evaluated clinical response, laboratory test, images with 111In-DOTATATE, 90Y, 177Lu, and 68Ga-DOTATATE PET/CT or CT. Results. We observed progression of disease in 10 (7,5 percent), partial remission in 25 (62,5 percent), stable disease in 3 (7,5 percent) and complete remission in 2 (5,0 percent). There was little toxicity without significant renal deterioration. We observed tumor mass reduction and improvement of quality of life in most of the patients. Conclusion. The therapy with radiopeptides is a safe and effective procedure in the treatment of advanced NET.