Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.

Review of imaging techniques for evaluating morphological and functional responses to the treatment of bone metastases in prostate and breast cancer.

Bone metastases are very common complications associated with certain types of cancers that frequently negatively impact the quality of life and functional status of patients; thus, early detection is necessary for the implementation of immediate therapeutic measures to reduce the risk of skeletal complications and improve survival and quality of life. There is no consensus or universal standard approach for the detection of bone metastases in cancer patients based on imaging. Endorsed by the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) a group of experts met to discuss and provide an up-to-date review of our current understanding of the biological mechanisms through which tumors spread to the bone and describe the imaging methods available to diagnose bone metastasis and monitor their response to oncological treatment, focusing on patients with breast and prostate cancer. According to current available data, the use of next-generation imaging techniques, including whole-body diffusion-weighted MRI, PET/CT, and PET/MRI with novel radiopharmaceuticals, is recommended instead of the classical combination of CT and bone scan in detection, staging and response assessment of bone metastases from prostate and breast cancer.Clinical trial registration: Not applicable.

Various Clinical Scenarios in Secondary Malignant Lymphedema.

Diagnosing malignant lymphedema is a challenge in daily clinical practice. Clinically, patients may show clear signs of malignancy, but this is not always the case, and at times the diagnosis is not straightforward. In some patients, pain, hardness of the tissues, joint stiffness, proximal involvement, collateral circulation, or an acute onset will provide the clue to determining malignancy. Our aim is to describe several diverse scenarios of Secondary Malignant Lymphedema (SML) with the etiopathogenesis. One possible cause is lymphatic obstruction due to extrinsic compression of lymphatic vessels and/or nodes by either the primary tumor or metastatic masses. Lymphatic obstruction can also be caused by tumoral infiltration. This infiltration can affect both deep and regional nodes as well as cutaneous and subcutaneous vessels and is commonly known as lymphangitis carcinomatosa. Malignant lymphedema can also be secondary to obstruction of the venous flow due to tumoral venous thromboembolism or to extrinsic compression of the veins by tumors or adenopathic masses. Nevertheless, the most frequent cause of this illness is a mixed mechanism of compression of the lymphatic and venous systems. Frequently, SML is the first manifestation of relapse. When lymphedema appears abruptly, is progressive, with intense pain, associated with collateral circulation, or with hard and infiltrated skin or joint stiffness, SML must be ruled out with an urgent referral to the oncologist and an imaging evaluation.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology)

Background and rationale Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. Methods/design TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being  > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient’s cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient’s death. Results After 18 months and with 35 centers and researchers, the registry has 1128 patients (AU)

Prevalence of clinical manifestations and orthopedic alterations in patients with lipedema: A prospective cohort study.

Lipedema is a chronic disease seen frequently in women that causes abnormal fat deposition in the lower limbs and associated bruising and pain. Despite increasing knowledge concerning lipedema, there are still aspects of diagnosis that need further investigation. We performed a prospective, observational cohort study to describe prevalence of clinical characteristics present in patients with lipedema in an attempt to establish diagnostic criteria. Participants were consecutive patients with lipedema presenting at a public hospital in Spain from September 2012 to December 2019. Patients were examined for the following signs and symptoms of lipedema: symmetrical involvement; disproportion between the upper and lower part of the body; sparing of the feet; pain; bruising; Stemmer' sign; pitting test; fibrosis; venous insufficiency; upper limbs involvement; vascular spiders; skin coldness; and lymphangitis attacks. In addition, orthopedic alterations were examined in all patients. We recruited 138 patients (median age=47.6 years; mean BMI=29.9 Kg/m2). Using waist-to-height-ratio, 41.3% of the patients were slim or healthy. The most frequent type of lipedema was Type III (71%), and most were in stage 1 and 2. The features of lipedema with a prevalence >80% were symmetrical involvement, unaffected feet, pain, bruising, vascular spiders, and disproportion. Pain was nociceptive in 60.2% and neuropathic in 33.1%, and there was a reduced social or working activities in 37.9%. Orthopedic alterations including cavusfeet or valgus-knees were observed in 1/3 of the patients. X-ray of the knees was performed in 63 patients and knee osteoarthritis diagnosed in 37. We found that the most frequent manifestations of lipedema were bilateral involvement, unaffected feet, pain, easy bruising, vascular spiders, and disproportion between the upper and lower parts of the body. These should be considered as major criteria for diagnosis. In addition, our findings on the prevalence of orthopedic alterations in patients with lipedema highlights the need for a multidisciplinary and integrated approach.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

La evaluación cuantitativa es esencial para la interpretación de la linfogammagrafía: respuesta a la carta al editor de Ramin Sadeghi / Quantitative assessment is essential for interpreting lymphoscintigraphy: Response to Ramin Sadeghi's letter to the editor

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SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018)

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents

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SEOM clinical guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2018).

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

Hallazgos linfogammagráficos en pacientes con lipedema / Lymphoscintigraphic findings in patients with lipedema

Introducción: El lipedema es un síndrome caracterizado por edema, acúmulo de grasa, dolor y hematomas en miembros inferiores que afecta principalmente a mujeres. Su diagnóstico actual se basa en criterios clínicos, dado que no tiene un diagnóstico de imagen de certeza. El objetivo de nuestro estudio fue describir los hallazgos linfogammagráficos observados en pacientes con lipedema. Material y método: Estudio de cohortes prospectivo de mujeres con criterios clínicos de lipedema a las que se realizó una linfogammagrafía. Dos médicos nucleares independientes describieron y clasificaron los hallazgos linfogammagráficos en diferentes grados de gravedad, en función de la migración y de la distribución del radiofármaco. Fueron incluidas 83 pacientes con una mediana de edad de 49,7años (rango: 18-80) y un índice medio de masa corporal (IMC) de 29,9kg/m2 (IC95%: 28,4-31,3). Resultados: En el 47% de las pacientes se observó alguna alteración en la linfogammagrafía, siendo en la mayoría de bajo grado (35,9%) o de grado bajo-moderado (48,7%). Ninguna presentó afectación severa (no migración del radiofármaco). El grado de afectación linfogammagráfica no presentó relación con la edad (p=0,674), ni con el signo de Stemmer (p=0,506), ni con el IMC (p=0,832). Encontramos hallazgos linfogammagráficos en todos los estadios clínicos de lipedema, sin diferencias significativas entre el grado de afectación linfogammagráfico y el estadio clínico del lipedema (p=0,142). Conclusión: Aunque la linfogammagrafía se ha empleado para diferenciar lipedema de linfedema, encontramos alteraciones frecuentes en las pacientes con lipedema, por lo que la presencia de hallazgos no descarta el diagnóstico de lipedema

Introduction: Lipedema is a syndrome that is characterised by edema, an accumulation of fat, pain and haematomas in the lower limbs that principally affects women. Diagnosis is currently based on clinical criteria, since there is no accurate diagnostic imaging for the condition. The aim of our study was to describe the lymphoscintigraphic findings in patients with lipedema. Material and method: A prospective cohort study of women with clinical criteria of lipedema who underwent lymphoscintigraphy. Two independent nuclear physicians described and classified the lymphoscintigraphy findings in different grades of severity, according to the migration and distribution of the radiopharmaceutical. Eighty three patients were included with a median age of 49.7years (range: 18-80) and a mean body mass index (BMI) of 29.9kg/m2 (95%CI: 28.4-31.3) Results: Lymphoscintigraphy showed alterations in 47% of the patients, most were low (35.9%) or low-moderate grade (48.7%). None of the patients were severely affected (no migration of the radiopharmaceutical). The degree of lymphoscintigraphic involvement bore no relation to age (P=.674), Stemmer's sign (P=.506), or BMI (P=.832). We found lymphoscintigraphy findings in all the clinical stages of lipedema, with no significant differences between the grade of lymphoscintigraphic involvement and the clinical stage of lipedema (P=.142). Conclusion: Although lymphoscintigraphy has been used to differentiate lipedema from lymphedema, we found frequent alterations in the patients with lipedema, therefore the presence of findings dues not discount a diagnosis of lip1aedema

Lymphoscintigraphic findings in patients with lipedema. / Hallazgos linfogammagráficos en pacientes con lipedema.

INTRODUCTION: Lipedema is a syndrome that is characterised by edema, an accumulation of fat, pain and haematomas in the lower limbs that principally affects women. Diagnosis is currently based on clinical criteria, since there is no accurate diagnostic imaging for the condition. The aim of our study was to describe the lymphoscintigraphic findings in patients with lipedema. MATERIAL AND METHOD: A prospective cohort study of women with clinical criteria of lipedema who underwent lymphoscintigraphy. Two independent nuclear physicians described and classified the lymphoscintigraphy findings in different grades of severity, according to the migration and distribution of the radiopharmaceutical. Eighty three patients were included with a median age of 49.7years (range: 18-80) and a mean body mass index (BMI) of 29.9kg/m2 (95%CI: 28.4-31.3) RESULTS: Lymphoscintigraphy showed alterations in 47% of the patients, most were low (35.9%) or low-moderate grade (48.7%). None of the patients were severely affected (no migration of the radiopharmaceutical). The degree of lymphoscintigraphic involvement bore no relation to age (P=.674), Stemmer's sign (P=.506), or BMI (P=.832). We found lymphoscintigraphy findings in all the clinical stages of lipedema, with no significant differences between the grade of lymphoscintigraphic involvement and the clinical stage of lipedema (P=.142). CONCLUSION: Although lymphoscintigraphy has been used to differentiate lipedema from lymphedema, we found frequent alterations in the patients with lipedema, therefore the presence of findings dues not discount a diagnosis of lip1aedema.

Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed

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Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.

SEOM clinical guideline of diagnosis and management of low-grade glioma (2017)

Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated. The precise optimal management of patients with low-grade glioma after resection remains to be determined. The risk-benefit ratio of adjuvant treatment must be weighed for each individual (AU)

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SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated. The precise optimal management of patients with low-grade glioma after resection remains to be determined. The risk-benefit ratio of adjuvant treatment must be weighed for each individual.

Correction to: SEOM clinical guideline of diagnosis and management of low-grade glioma (2017).

The original version of this article unfortunately contained a mistake. Figure 3 was incorrect.

Iron deficiency in patients with solid tumours: prevalence and management in clinical practice

PURPOSE: The objective of the present study was to describe the prevalence and management of anaemia and iron deficiency (ID) in treatment-naïve patients with solid tumours in Spain and the incidence of anaemia over 4 months of cancer treatment in clinical practice. METHODS: Multicentre, prospective and observational study in newly diagnosed cancer patients. Data on anaemia and iron parameters and its management were collected prior to the initiation of chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The main outcomes of the study were the prevalence of anaemia at baseline, its incidence during cancer treatment and the prevalence of absolute ID (AID) and functional ID (FID) prior to chemotherapy initiation. RESULTS: A total of 295 patients were included in the study. Anaemia was present at diagnosis in 38.6 % of patients and was treated only in 32.5 % of those. A total of 106 patients (60.2 %) without anaemia at baseline developed anaemia during cancer treatment. Serum ferritin and transferrin saturation data were available for 151 of the patients (51.2 %) included in the study. The overall prevalence of ID was 59 %: 48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron-deficient patients did not receive any type of iron supplementation before initiating cancer therapy. CONCLUSIONS: Iron parameters are not commonly measured in newly diagnosed cancer patients. A correct evaluation and early management of ID could reduce the incidence of treatment-related anaemia in cancer patients (AU)

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Iron deficiency in patients with solid tumours: prevalence and management in clinical practice.

PURPOSE: The objective of the present study was to describe the prevalence and management of anaemia and iron deficiency (ID) in treatment-naïve patients with solid tumours in Spain and the incidence of anaemia over 4 months of cancer treatment in clinical practice. METHODS: Multicentre, prospective and observational study in newly diagnosed cancer patients. Data on anaemia and iron parameters and its management were collected prior to the initiation of chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The main outcomes of the study were the prevalence of anaemia at baseline, its incidence during cancer treatment and the prevalence of absolute ID (AID) and functional ID (FID) prior to chemotherapy initiation. RESULTS: A total of 295 patients were included in the study. Anaemia was present at diagnosis in 38.6 % of patients and was treated only in 32.5 % of those. A total of 106 patients (60.2 %) without anaemia at baseline developed anaemia during cancer treatment. Serum ferritin and transferrin saturation data were available for 151 of the patients (51.2 %) included in the study. The overall prevalence of ID was 59 %: 48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron-deficient patients did not receive any type of iron supplementation before initiating cancer therapy. CONCLUSIONS: Iron parameters are not commonly measured in newly diagnosed cancer patients. A correct evaluation and early management of ID could reduce the incidence of treatment-related anaemia in cancer patients.