lutetium-lu-177-dotatate and Lung-Neoplasms

Bronchial carcinoids are uncommon tumors accounting for 20 to 30% of all neuroendocrine tumors and about 1-2% of all cancers of pulmonary origin. Bronchial carcinoids are well-differentiated neuroendocrine tumors and have a favorable survival outcome when compared with other subtypes of lung cancers. Treatment of bronchial carcinoids is not simple owing to intricacy of symptom presentation and heterogeneity of disease biology. Successful treatment of patients requires a multimodality approach. Resection is curative in the majority of patients with localized tumors and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced disease. To date, very few randomized clinical trials have been done, partly owing to the relative rarity of this malignancy. Somatostatin analogs (SSAs) are reasonable first-line choice for patients with tumors expressing somatostatin receptors. Everolimus is an appropriate first-line choice for somatostatin receptor negative tumors and for any patients with progressive disease. PRRT can also be considered for progressive tumors expressing somatostatin receptors. Based on retrospective series, cytotoxic chemotherapy can be selected in patients with progressive tumors, primarily when cytoreduction is needed. Herein, we will discuss evidence supporting the role of adjuvant and systemic treatment therapies for those with bronchial carcinoid tumors by focusing on various studies.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bronchial Neoplasms; Capecitabine; Carcinoid Tumor; Chemotherapy, Adjuvant; Cisplatin; Etoposide; Everolimus; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Lymph Node Excision; Molecular Targeted Therapy; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pneumonectomy; Protein Kinase Inhibitors; Radiopharmaceuticals; Receptors, Somatostatin; Somatostatin; Temozolomide; Watchful Waiting

Topics: Carcinoid Tumor; Carcinoma, Neuroendocrine; Clinical Trials as Topic; Humans; Lung Neoplasms; Molecular Targeted Therapy; Neoplasm Staging; Octreotide; Organometallic Compounds; Peptides; Receptors, Somatostatin; Somatostatin; Treatment Outcome

Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system.. To estimate the clinical effectiveness of three interventions [everolimus (Afinitor. The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science.. We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel. Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin. A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials.. Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales.. Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial.. This study is registered as PROSPERO CRD42016041303.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Digestive System Neoplasms; Disease Progression; Everolimus; Humans; Lung Neoplasms; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality-Adjusted Life Years; Radioisotopes; Randomized Controlled Trials as Topic; Sunitinib

Lutathera is a. Patients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).. Nine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.. Lutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.. NCT03325816.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Nivolumab; Octreotide; Organometallic Compounds

We represent the case of a 61-year-old man with atypical carcinoid tumor of the lung. On posttherapy 177Lu-DOTATATE whole-body scan, focal intense uptake in the inferomedial side of the liver was detected. Pretherapy 68Ga-DOTATATE PET/CT showed no sign of liver metastasis, and posttherapy diagnostic dynamic liver MRI is used to exclude metastatic liver disease. Focal intense uptake was attributed to physiological gallbladder uptake.

Topics: Biological Transport; Gallbladder; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Whole Body Imaging

We report here the 12-year survival after the first peptide receptor radionuclide therapy (PRRT) of a patient with metastatic rectal neuroendocrine neoplasms, who received 7 cycles of PRRT with Lu/Y-DOTATATE/DOTATOC in 4 treatment phases. The patient demonstrated excellent response to each cycle of treatment, without any adverse effect even after repeated PRRT cycles. Most recently, immunohistochemistry revealed a G3 neuroendocrine neoplasm and intraspinal metastasis were successfully resected by neurosurgical intervention. This case nicely demonstrates that several "salvage" PRRTs can be given over many years leading to repetitive benefit for the patient and saving patients of possible toxicity of alternative treatments.

Topics: Adult; Bone Neoplasms; Heart Neoplasms; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Radiotherapy; Rectal Neoplasms; Salvage Therapy; Treatment Outcome

Meningiomas are typically benign solitary intracranial tumors. Atypical (World Health Organization [WHO] grade II) or malignant/anaplastic (WHO grade III) meningiomas are seldom, and distant metastases occur only in rare exceptions. We present a case of a 54-year-old male patient with atypical (WHO grade II) meningioma who underwent 1 cycle of peptide receptor radionuclide therapy. Previous imaging studies were confined to the head, but posttherapeutic whole-body Lu-DOTATATE scintigraphy revealed thoracic uptake arising from previously undetected pulmonic meningioma metastases. The case highlights the importance of consideration of rare/untypical metastatic sides and the value of radiotracer whole-body imaging in identifying these.

Topics: Humans; Lung Neoplasms; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Single Photon Emission Computed Tomography Computed Tomography

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a high-grade, poorly differentiated tumor that typically does not express somatostatin receptors. Thus, it does not benefit from treatment with somatostatin analogs and peptide receptor radionuclide therapy (PRRT). The current study objective was to demonstrate that treatment with PRRT may be a valid option in neuroendocrine carcinomas with high expression of somatostatin receptors. This is a case report of a 58-year-old man who was diagnosed with LCNEC and received chemotherapy treatment with little benefit. Extensive hepatic and bone metastasis was detected on

Topics: Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Quality of Life; Treatment Outcome

The aims of this study were to perform multiparametric response assessment of metastatic/advanced pulmonary neuroendocrine tumors (NETs) to Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) (clinical, biochemical, molecular/structural imaging, and survival assessment) and to study the relationship between response, mortality, and overall survival with dual-tracer molecular imaging parameters.. Twenty-two patients (6 women, 16 men; median age, 44 years; range, 16-72 years) of histopathologically proven pulmonary NETs with metastatic/advanced disease were included and analyzed retrospectively. Lu-DOTATATE PRRT was administered using standardized protocol (150 mCi [5.55 GBq] per cycle, cycles repeated at 12-16 weeks' intervals [range, 1-5 cycles; average, 4 cycles]) with amino acid-based renal protection. Assessment with Tc-HYNIC-TOC (in the initial years of PRRT development, n = 11)/Ga-DOTATATE PET/CT (presently, n = 11) and F-FDG PET/CT (n = 22), symptomatic and biochemical parameters (serum CgA and urinary 5-HIAA levels), and anatomical response using contrast-enhanced CT (after 3 cycles) was part of routine pretreatment and response evaluation. The patients were designated as responders and nonresponders based on predefined response assessment criteria. Kaplan-Meier product-limit method was calculated for overall survival (OS) curve after the first PRRT, and corresponding 95% confidence intervals (95% CIs) were estimated for annual survival at 1, 2, 3, and 4 years. The various prognostic variables were also investigated for association with mortality, OS, and treatment response following PRRT.. Of 22 patients, 6 had undergone surgical resection of primary tumors. All patients were symptomatic before start of PRRT. Two patients did not qualify for PRRT, and 1 received single cycle with follow-up less than 3 months, hence excluded from the present analysis. Thus, a total 19 patients were analyzed in our study. Symptomatic response following PRRT was observed in 15 (79%) of 19 patients. Based on predefined 3-scale response evaluation criteria, of 19 patients, 12 patients (63%) were finally characterized as responders, and 7 patients (37%) were overall nonresponder to PRRT. All 7 nonresponders had moderate to intense FDG-avid primary lung lesion (SUVmax >5 in 4 of 7 patients), and 5 had FDG-avid metastatic liver disease (SUVmax >5). Peptide receptor radionuclide therapy was well tolerated in all with no major hematologic and renal toxicity (except for 2 patients showing mild grade I renal and hematologic toxicity in the initial cycles and recovery in subsequent follow-up). Seven (37%) of 19 died at the time of analysis. The observed annual OS rates were as follows: 1 year: 94.7% (95% CI, 68.1%-99.2%), 2 years: 66% (95% CI, 35.5%-84.5%), 3 years: 57.7% (95% CI, 28-78.9%), and 4 years: 38.5% (95% CI, 8.1%-69.5%); median OS was 40 months with 39% (95% CI, 13.1%-64.8%). In conclusion, Lu-DOTATATE PRRT was found safe and well tolerated in receptor-positive pulmonary NET. FDG positivity appeared to forecast aggressive tumor behavior.

Topics: Adolescent; Adult; Aged; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Positron Emission Tomography Computed Tomography; Prognosis; Receptors, Peptide; Retrospective Studies; Treatment Outcome; Young Adult

Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT).. In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT.. Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by (68)Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using (177)Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months.. Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC.

Topics: Animals; Antineoplastic Agents; Carboplatin; Carcinoma, Small Cell; Cell Line, Tumor; Etoposide; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Octreotide; Organometallic Compounds; Radiopharmaceuticals; Receptors, Somatostatin; Small Cell Lung Carcinoma; Translational Research, Biomedical

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT.. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen.. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs.. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC.

Topics: Aged; Bone Neoplasms; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Organotechnetium Compounds; Radiopharmaceuticals; Receptors, Somatostatin; Sensitivity and Specificity; Time Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

Topics: Blood-Brain Barrier; Coordination Complexes; Disease Progression; Female; Humans; Lung Neoplasms; Meningioma; Middle Aged; Neoplasm Metastasis; Octreotide; Positron-Emission Tomography; Quality of Life; Radiopharmaceuticals; Receptors, Peptide; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Outcome

Peptide-receptor radionuclide therapy (PRRT) with somatostatin analogs is an efficient new tool in patients with neuroendocrine tumors, with low risk of toxicity. Since lymphocytes express somatostatin receptors, the aim of this study was to evaluate lymphocytic toxicity after PRRT.. From May 2005 to May 2007, 16 patients affected by neuroendocrine tumors received PRRT with (90)Y-DOTATOC (9), (177)Lu-DOTATATE (5), or both (2). Absolute count, percentage of leukocytes and lymphocytes, and lymphoid subsets (B, T, and NK) were tested at baseline and until 90 days after treatment.. A significant lymphoid toxicity (G2-3), mainly affecting B-cells, was observed. It was particularly evident after (90)Y-DOTATOC. Toxicity resulted in being transient and resolved completely at the end of the follow-up (90 days).. Lymphocyte toxicity in PRRT is mainly due to the selective targeting on B-cells. The relative sparing of T-lymphocytes could explain the absence of clinical side-effects in these patients, such as increased risk of infections. These findings open interesting perspectives in the treatment of B-cell lymphoproliferative disorders.

Topics: Adult; Aged; B-Lymphocytes; Colonic Neoplasms; Duodenal Neoplasms; Female; Humans; Ileal Neoplasms; Lung Neoplasms; Lutetium; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Yttrium Radioisotopes

(177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice.. Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24 hours postinjection (hpi). The results were compared with earlier published biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the same animal model.. The activity concentration of (111)In-DTPAoctreotide in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24 hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu-DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was significantly higher in the heart, lungs, liver, the salivary glands, spleen, and bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the somatostatin receptors may have influenced the uptake in tumor and sstr-positive normal tissues.. The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.

Topics: Animals; Carcinoma, Small Cell; Cell Line, Tumor; Disease Models, Animal; Humans; Indium Radioisotopes; Liver; Lung; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Octreotide; Organometallic Compounds; Organotechnetium Compounds; Pentetic Acid; Radiopharmaceuticals; Somatostatin; Time Factors; Tissue Distribution

Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using 111In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr3-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid), labeled with the medium-energy electron emitter 177Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model.. Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with 177Lu-DOTA-Tyr3-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr3-octreotate and another control group was not treated.. In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with 177Lu-DOTA-Tyr3-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 +/- 0.004.. Radiation therapy with 177Lu-DOTA-Tyr3-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with 177Lu-DOTA-Tyr3-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.

Topics: Animals; Carcinoma, Small Cell; Disease Models, Animal; Injections, Intravenous; Lung Neoplasms; Male; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Mice, Nude; Octreotide; Organ Specificity; Organometallic Compounds; Radiopharmaceuticals; Tissue Distribution; Treatment Outcome