Juan Jesús Cruz Hernández

SEOM clinical guidelines for the treatment of head and neck cancer

Head and neck cancer constitutes the fifth highest cause of cancer in Spain. It is a neoplasm with a high possibility of cure if it is diagnosed in early stages, but unfortunately two thirds of the patients are diagnosed at an advanced loco-regional stage (stage III and IV, without metastasis). The multidisciplinary team, bringing together all professionals who specialize in the diagnosis and treatment of these tumors make the decision to establish the best sequence of individualized diagnosis, staging and treatment for each patient. This guide gives recommendations for diagnosis, staging and treatment for squamous cell carcinoma of the head and neck. In order to simplify the amount of information about any subsite of the head and neck area, the treatment recommendations are summarized as local disease, locally advance resectable and unresectable stages, function-preserving laryngeal treatment and recurrent and metastatic disease.

Durable clinical benefit with exemestane in leptomeningeal metastasis of breast cancer

Since most chemotherapy agents do not cross the blood brain barrier, the classical approach for leptomeningeal metastasis (LM) of breast cancer is the administration of cranial intra-ventricular chemotherapy. The roles of hormonal agents like tamoxifen and aromatase inhibitors in LM treatment are not clear. We report the case of a patient with leptomeningeal metastasis from breast cancer with longterm stabilisation using exemestane. Although the ideal therapy for LM remains under dedate, hormonal therapy can contribute towards maintaining the response in some patients with LM and hormonepositive breast cancer.

SEOM clinical guidelines for the treatment of nasopharyngeal carcinoma

Nasopharyngeal carcinoma is an unusual tumour in Spain. It has differences in epidemiology, histology, clinical behaviour, treatment and prognosis from those of other head and neck neoplasms, which justifies separate analysis. It is a neoplasm with a high possibility of cure with a combined treatment if even it is diagnosed in an advanced locoregional stage (stage III or IV, without metastasis). The multidisciplinary team, bringing together all professionals who specialize in the diagnosis and treatment of these tumors make the decision to establish the best sequence of individualized diagnosis, staging and treatment for each patient. This guide gives recommendations for diagnosis, staging and treatment for nasopharyngeal carcinoma. The treatment recommendations are summarized as local disease, locally advance and recurrent and metastatic disease.

SEOM clinical guidelines: a consolidated project

In this issue of Clinical and Translational Oncology, the Spanish Society of Clinical Oncology (SEOM) publishes the third part of the SEOM’s Clinical Practice Guidelines. Since November 2010, when the first guidelines issue was published, this project has been received with enthusiasm among the Spanish oncology community, reinforcing the need for new guidelines covering all the areas of interest of medical oncologists. Ten new guidelines are now published. Three of these guidelines review the recommendations in some of the most important topics in supportive care and symptom control. As the authors describe, myelosuppression associated with chemotherapy has been a major limitation of patient tolerance to antineoplastic treatment and the clinical consequences of this myelosuppression can have a negative effect on the quality of life of patients or even diminish treatment efficacy and patient survival [1]. Moreover, treatment and prophylaxis of neutropenia and febrile neutropenia with myeloid growth factors varies very much in clinical practice, leading to the need to generalise and facilitate practice based on clinical evidence [1]. The treatment of bone metastasis from solid tumours has been one of the most challenging areas in recent months as a result of a better understanding of the physiopathology of bone metastasis and the development of agents directed against molecular pathways related to this process. In addition, the authors remark that the development of skeletal related events is a frequent complication of these metastases that profoundly alters the quality of life of patients, significantly increases healthcare costs and is associated with increased mortality [2], making these guidelines an essential tool for practitioners. Regarding pain management, the guidelines published in this issue represent a schematic and practical review with a special interest in the management of cancerrelated breakthrough pain with rapid-onset opioids [3]. The other seven articles are focused on the management of different solid tumours. Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract and, as the authors describe, have become a model of multidisciplinary work in oncology: the participation of several specialities (oncologists, pathologists, surgeons, molecular biologists, radiologists,...) has allowed advances in the understanding of this tumour and the consolidation of targeted therapies [4], reinforcing the role of practical guidelines that summarise the recent scientific evidence. The purpose of the gastric cancer clinical guidelines is to provide recommendations for the diagnosis and treatment of this disease based on the best available evidence. Regarding resectable gastric cancer, the various potential therapeutic options are discussed by the experts. For advanced disease, different alternative combinations of conventional cytotoxic agents, as well as their integration with new biological agents (mainly trastuzumab in HER2+ tumours), are discussed. An outline is also provided of the main lines of research and development of therapies for this disease [5]. There is no doubt about the growing interest in the treatment of prostate cancer–the most frequent malignant tumour in men. Recent advances in the management of advanced disease and especially castration-resistant prostate cancer are reported; and data coming from trials with several therapeutic procedures such as sipuleucel-T, docetaxel-based chemotherapy, radium 223, cabazitaxel or abiraterone plus prednisone, zoledronic and denosumab, among others, are reviewed [6]. Two of the new guidelines are focused on gynaecologic cancer. Cancer of the cervix is one of the most frequent malignant tumours worldwide, especially in developing countries, where it is often a leading cause of cancer-related death. Several major aspects are of special interest in this clinical entity: cancer of the cervix affects individuals at a younger age than other cancers; programmes of J.J. Cruz Hernández Chairman of The Spanish Society of Medical Oncology (SEOM) Servicio de Oncología Médica Hospital Clínico Universitario Salamanca, Spain

Renal Cell Carcinoma Associated With Xp11.2 Translocation/TFE3 Gene-fusion: A Long Response to mammalian target of rapamycin (mTOR) Inhibitors

OBJECTIVE To demonstrate that patients with Xp11.2/TFE3 gene-fusion translocation renal cell carcinoma (RCC), despite having an aggressive course in young adults, could have valid treatment options such as mammalian target of rapamycin (mTOR) inhibitors with good outcomes. Furthermore, to explain possible mechanisms of action of mTOR inhibitors in this type of RCC. MATERIALS AND METHODS We report a case of a 44-year-old man who has been treated with everolimus for a Xp11.2 translocation/TFE3 gene-fusion RCC after 2 previous failed treatments with tyrosine kinase inhibitor. During the follow-up, we evaluated type and duration of response with everolimus. RESULTS The patient obtained a long-lasting response of disease of 25 months with everolimus without any symptom. CONCLUSION We believe that mTOR inhibitors could be a good line option treatment to consider for this type of patients.

Large cell neuroendocrine carcinoma of the lung with atypical evolution and a remarkable response to lutetium Lu 177 dotatate

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 111In-pentetreotide scintigraphy following high uptake of the radionuclide by the tumors. The patient benefitted from neuroendocrine treatment initially and from lutetium Lu 177 dotatate subsequently. A significant clinical and radiological response was observed, along with an improvement in quality of life. The use of PRRT is a valid alternative to chemotherapy in patients with LCNEC involving the expression of somatostin receptors.

Estudio de la expresión de ciclina D1, p16, MIB-1 y p53 en lesiones precancerosas orales

ResumenObjetivosConocer la expresión proteica de las alteraciones genéticas que se producen en las etapas precoces de la cancerización del campo de cavidad oral en nuestro medio. Estudiar la expresión proteica de MIB-1, ciclina D1, p16 y p53 para valorar si las alteraciones en la expresión proteica de estos marcadores suceden de forma secuencial a través de las distintas etapas en la cancerización del campo de cavidad oral.Material y métodosSe realizó un estudio mediante técnicas de inmunohistoquímica sobre 53 pacientes que presentaron lesiones de leucoplasia oral. Se incluyen en el estudio 11 muestras de epitelio normal, 15 displasias leves y moderadas, 15 carcinomasin situ y 12 carcinomas microinvasores.ResultadosEncontramos sobreexpresión de MIB-1, ciclina D1 y p53 y pérdida de expresión de p16 a medida que avanzamos en el grado de severidad histopatológica de las lesiones. Las alteraciones más precoces son sobreexpresión de MIB-1 y pérdida de expresión de p16 en displasias leves y moderadas. Hay diferencias significativas en la expresión de ciclina D1 entre displasias leves y moderadas y carcinomasin situ.ConclusionesLa leucoplasia oral es un estado precanceroso que constituye una lesión que se puede transformar en maligna debido a las alteraciones genéticas que intervienen en la evolución de la lesión. El estudio inmunohistoquímico y molecular de las lesiones es un medio rutinario que permite conocer la expresión proteica de las alteraciones genéticas, que puede ayudar en el diagnóstico precoz y tratamiento de esta patología, teniendo especial relevancia el estudio de p16 en etapas iniciales y p53 en lesiones más avanzadas.Abstract|AimsTo know the proteic expression of the genetic alterations that take place in the precocious stages of the field cancerization of oral cavity in our means. To study the MIB-1, cyclin D1, p16 and p53 expression levels to value if the alterations in the expression levels of these markers happen in a sequential pathway through the different stages in the field cancerization of oral cavity.|Material and methodsWe have studied by means of technical of immunohistochemistry on 53 patients with oral leucoplakia. They are included in the study 11 specimens of normal squamous epithelium, 15 mild and moderate dysplasias, 15in situ carcinomas and 12 microinvasive carcinomas.|ResultsOverexpression of MIB-1, cyclin D1 and p53 and loss of p16 expression was found as we increased in the grade of histopathological severity of the lesions. The most precocious alterations are overexpresion of MIB-1 and loss of p16 expression in mild and moderate dysplasic lesions. There are significant differences in the expression of cyclin D1 between light and moderate dysplasias andin situ carcinomas.|ConclusionsThe oral leucoplakia is a precancerous condition that constitutes a possible malignant transformation in oral carcinoma due to the genetic alterations that partipate in the evolution of the lesion. The immunohistochemistry and molecular study of the lesions is a routine means to make it possible to know the proteic expression of the genetic alterations that can help in the precocious diagnosis and treatment of this pathology, having special relevance the study of p16 expression in initial stages and p53 in more advanced lesions.

Metástasis ovárica de cáncer de mama en mujer portadora de mutación en BRCA1

Ovarian metastasis as the unique site of breast cancer relapse is infrequent. We describe the case of a woman diagnosed as having breast cancer and who presented single-site metastasis in the ovaries 14 years after the initial diagnosis. The patient was a carrier of a mutation in the BRCA1 gene (C1806T, Q563X) which, to date, had not been described in the spanish population.

Massive intra-peritoneal non-functioning malignant paraganglioma

ResumenSe presenta el caso de una mujer con dolor abdominal y masa palpable. El nivel de catecolaminas fue normal. En la intervención quirúrgica se identificó y extirpó una gran tumoración abdominopélvica. No había infiltración de estructuras retroperitoneales, tracto gastrointestinal, vejiga ni genitales internos. El tumor mostró diseminación peritoneal con varios implantes en el omento mayor y en el peritoneo. Se realizó una excisión completa de la masa y de los implantes peritoneales. En el examen patológico se confirmó el diagnóstico de paraganglioma. Tras 4 meses recidivó con adenopatías retroperitoneales y metástasis hepáticas. No hubo respuesta tras tres ciclos de quimioterapia basada en platino. Otros tres ciclos más de ciclofosfamida, vincristina y dacarbacina (DTIC) se administraron sin obtener respuesta. Ocho meses después se realizó una segunda intervención con fin citorreductor. La paciente falleció debido a progresión tumoral.Los paragangliomas no funcionantes son tumores raros que ocasionalmente se presentan como masas intraabdominales que se asemejan a los tumores ováricos. Generalmente asintomáticos, se pueden presentar como grandes tumores. El paraganglioma abdominal debe ser tenido en cuenta para establecer diagnóstico diferencial en las masas abdominopélvicas.