SEOM-GETNE clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2022)

'Neuroendocrine neoplasms (NENs) are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise mainly due to an improvement on diagnostic techniques and awareness. Earlier detection, along with steadfast improvements in therapy, has led to better prognosis over time for advanced gastrointestinal and pancreatic neuroendocrine tumors. The aim of this guideline is to update evidence-based recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification, and therapeutic options, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are reviewed and discussed, and treatment algorithms to guide therapeutic decisions are provided (AU)

Case Report: Re-Treatment With Lu-DOTATATE in Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) is an established treatment in advanced neuroendocrine tumors (NETs), which overexpressed somatostatin receptors. However, after progression there are a limited number of available treatments. We want to share a case report about a patient with a NET re-treated with 177Lu-DOTATATE and a literature review about salvage treatment with PRRT. We present a 26-year-old man who started with pelvic pain and after a biopsy of a retro-rectal mass observed in a magnetic resonance was diagnosed with an advanced neuroendocrine tumour. After progression to lanreotide, everolimus and sunitinib, treatment with 177Lu-DOTATATE was initiated, achieving an excellent response with a progression free survival (PFS) of 38 months. At the time of progression, re-treatment with 177Lu-DOTATATE was decided, showing a new partial response, which is currently stable after 15 months. The patient had not presented significant treatment-related toxicity. Although there are no randomized phase III trials or a consensus about the number or dose of cycles, there is evidence about the efficacy and low toxicity of salvage treatment with 177Lu-DOTATATE in NETs. Median progression-free survival ranges from 6 to 22 months. Toxicity is mostly hematologic (anemia and neutropenia), 4-7% grade 3/4.

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma / Consenso español para el tratamiento de los pacientes con carcinoma anaplásico de tiroides

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean overall survival has not improved in the past 50 years

El cáncer anaplásico de tiroides (CAT) es el tumour sólido más agresivo conocido y es una forma rara pero muy letal de cáncer de tiroides que requiere un enfoque multidisciplinario. No existe ningún consenso español para definir la conducta a seguir en los pacientes con CAT. El Grupo de Cáncer de Tiroides de la Sociedad Española de Endocrinología y Nutrición y el GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) de la Sociedad Española de Oncología, de acuerdo con las Juntas Directivas de estas Sociedades decidieron que un grupo de trabajo independiente desarrollaran un amplio consenso sobre el CAT. Se revisó la literatura relevante, incluyendo la búsqueda en PubMed de las series más relevantes. En el consenso se incluyen las características, el diagnóstico, la evaluación inicial, el establecimiento de los objetivos del tratamiento, la actitud a seguir ante la enfermedad locorregional (cirugía, radioterapia, terapia sistémica, la atención de apoyo durante el tratamiento activo), acerca a la enfermedad avanzada/metastásica, las opciones de cuidados paliativos, la vigilancia y el seguimiento a largo plazo del CAT. Para la enfermedad operable, la combinación de la cirugía radical con radioterapia o quimioterapia adyuvante, utilizando agentes tales como doxorrubicina, cisplatino y paclitaxel, es la mejor estrategia de tratamiento. Los fármacos citotóxicos para los casos avanzados/metastásicos de CAT son poco eficaces. Por otra parte, los agentes dirigidos a dianas específicas pueden representar una opción terapéutica viable. Los pacientes con enfermedad resecable en estadio IVA/IVB tienen el mejor pronóstico, sobre todo si se utiliza un enfoque multimodal, y algunos pacientes no resecables etapa IVB pueden responder a una terapia agresiva. En los pacientes con enfermedad en estadio IVC se debe considerar o bien si son aptos para entrar en un ensayo clínico o bien para cuidados paliativos, dependiendo de la preferencia del paciente. Este es el primer consenso español para el CAT y ofrece recomendaciones para la conducta a seguir en este tumour maligno extremadamente agresivo. Las terapias sistémicas más recientes están siendo evaluadas, y se necesitan combinaciones más eficaces para mejorar los resultados en los pacientes tratados. Aunque la radioterapia más agresiva ha reducido las recurrencias locorregionales, la media de supervivencia global no ha mejorado en los últimos 50 años

Spanish consensus for the management of patients with anaplastic cell thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is the most aggressive solid tumour known and is a rare but highly lethal form of thyroid cancer that requires a multidisciplinary team approach. No Spanish consensus exists for management of patients with ATC. The Thyroid Cancer Group of the Spanish Society of Endocrinology and Nutrition and the GETHI (Grupo Español de Enfermedades Huérfanas e Infrecuentes) of the Spanish Society of Oncology, in agreement with the Boards of these Societies, commissioned an independent task force to develop a wide consensus on ATC. The relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The consensus includes the characteristics, diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active treatment), approaches to advanced/metastatic disease, palliative care options, monitoring, and long-term follow-up of ATC. For operable disease, a combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin, cisplatin and paclitaxel, is the best treatment strategy. Cytotoxic drugs are poorly effective for advanced/metastatic ATC. On the other hand, targeted agents may represent a viable therapeutic option. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for clinical trials or for hospice/palliative care depending on their preference. This is the first Spanish consensus for ATC, and provides recommendations for management of this extremely aggressive malignancy. Novel systemic therapies are being tested, and more effective combinations are needed to improve patient outcomes. Although more aggressive radiotherapy has reduced locoregional recurrence, mean overall survival has not improved in the past 50 years.

New insights into molecular mechanisms of sunitinib-associated side effects.

The introduction of targeted therapy represents a major advance in the treatment of tumor progression. Targeted agents are a novel therapeutic approach developed to disrupt different cellular signaling pathways. The tyrosine kinase inhibitor sunitinib specifically blocks multiple tyrosine kinase receptors that are involved in the progression of many tumors. Sunitinib is the current standard of care in first-line treatment of advanced renal cell carcinoma, and it is approved in imatinib-intolerant and imatinib-refractory gastrointestinal stromal tumors. However, it is increasingly evident that sunitinib may display collateral effects on other proteins beyond its main target receptors, eliciting undesirable and unexpected adverse events. A better understanding of the molecular mechanisms underlying these undesirable sunitinib-associated side effects will help physicians to maximize efficacy of sunitinib and minimize adverse events. Here, we focus on new insights into molecular mechanisms that may mediate sunitinib-associated adverse events.

Stem cell and lung cancer development: blaming the Wnt, Hh and Notch signalling pathway.

Primary lung cancer may arise from the central (bronchial) or peripheral (bronchiolo-alveolar) compartments. However the origins of the different histological types of primary lung cancer are not well understood. Stem cells are believed to be crucial players in tumour development and there is much interest in identifying those compartments that harbour stem cells involved in lung cancer. Although the role of stem cells in carcinogenesis is not well characterised, emerging evidence is providing new insights into this process. Numerous studies have indicated that lung cancer is not a result of a sudden transforming event but a multistep process in which a sequence of molecular changes result in genetic and morphological aberrations. The exact sequence of molecular events involved in lung carcinogenesis is not yet well understood, therefore deeper knowledge of the aberrant stem cell fate signalling pathway could be crucial in the development of new drugs against the advanced setting.

Melanoma: from darkness to promise.

Metastatic melanoma is one of the most resistant tumors to standard chemotherapy approaches. The median overall survival of patients diagnosed with metastatic melanoma is lower than 9 months. Current approved treatments offer only marginal survival advantages. New immunotherapeutic targets have appeared recently trying to modulate the host immune response against the tumor. New targeted agents have changed the standard of care of other solid tumor types like breast cancer. Here, we discuss the new advances and achievements in the treatment of this highly resistant disease.

Old and new insights in the treatment of thyroid carcinoma.

Thyroid cancer is the endocrine tumor that bears the highest incidence with 33 550 new cases per year. It bears an excellent prognosis with a mortality of 1530 patients per year (Jemal et al.; 2007). We have been treating patients with thyroid carcinoma during many years without many innovations. Recently, we have assisted to the development of new agents for the treatment of this disease with unexpected good results. Here we present a review with the old and new methods for the treatment of this disease.

Final Report of the First Refractory Germ Cell Tumor Treated with Sunitinib Malate.

Patients with advanced germ cell tumors can be cured with cisplatin-based chemotherapy, but the outcome remains unsatisfactory for patients with relapsed disease, including those patients with refractory disease after bone marrow transplantation. Targeted therapies have changed the standard of care for many advanced solid tumors. We have identified, in the literature, potential targets for the treatment of refractory germ cell tumors, and applied to a patient with a refractory disease. We chose sunitinib for this purpose. To our knowledge, this is the first case to be treated with sunitinib, and we have found a promising activity.

Cancer and immune response: old and new evidence for future challenges.

Cancer may occur as a result of abnormal host immune system tolerance. Recent studies have confirmed the occurrence of spontaneous and induced antitumor immune responses expressed as the presence of tumor-infiltrating T cells in the tumor microenvironment in some cancer models. This finding has been recognized as a good prognostic factor in several types of tumors. Some chemotherapy agents, such as anthracyclines and gemcitabine, are effective boosters of the immune response through tumor-specific antigen overexpression after apoptotic tumor cell destruction. Other strategies, such as GM-CSF or interleukin-2, are pursued to increase immune cell availability in the tumor vicinity, and thus improve both antigen presentation and T-cell activation and proliferation. In addition, cytotoxic T lymphocyte antigen 4-blocking monoclonal antibodies enhance immune activity by prolonging T-cell activation. Strategies to stimulate the dormant immune system against tumors are varied and warrant further investigation of their applications to cancer therapy in the future.

Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies.

INTRODUCTION: CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. MATERIAL AND METHODS: We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). RESULTS: CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. CONCLUSIONS: The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.

Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies

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Introduction. CNS metastases mean a great challenge.It has been suggested that the brain metastasesincidence could be high in metastasic breastcancer patients receiving trastuzumab based-therapies.Material and methods. We performed a descriptiveanalysis of our experience in this setting. 86 patientsmet the criteria (From Oct/99 to Oct/03).Results. CNS progression occurred in 17 patients(19.5%). Mean age of CNS progression disease patientswas 45.4 years while mean age for all the patientswas 50.5 years. Response rate for the entiregroup of patients was: OR 39.7%; CB (OR + SD)69%. Response rate to trastuzumab based-therapywas OR 82.4% and CB 88.2 at the time of CNS progression.Median time from the start of trastuzumabtherapy up to the CNS progression was 10 months.OS was 23.4 weeks.Conclusions. The incidence of CNS involvement ishigh in young metastasic breast cancer women respondingto trastuzumab-based therapies. This maylead to prophylactic cranial irradiation strategies orto the early detection in asymptomatic patients toimprove surgery or radiosurgery results in these patients

Epidemiología de las tromboembolias pulmonares asintomáticas en los pacientes con cáncer. Réplica / Epidemiology of asymptomatic pulmonary embolism in cancer patients. Reply

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