Update on the management of elderly patients with colorectal cancer

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans (AU)

Update on the management of elderly patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

Development and Validation of an Early Mortality Risk Score for Older Patients Treated with Chemotherapy for Cancer.

Background: Estimation of life expectancy in older patients is relevant to select the best treatment strategy. We aimed to develop and validate a score to predict early mortality in older patients with cancer. Patients and Methods: A total of 749 patients over 70 years starting new chemotherapy regimens were prospectively included. A prechemotherapy assessment that included sociodemographic variables, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and early death was examined using multivariable logistic regression. Score points were assigned to each risk factor. External validation was performed on an independent cohort. Results: In the training cohort, the independent predictors of 6-month mortality were metastatic stage (OR 4.8, 95% CI [2.4-9.6]), ECOG-PS 2 (OR 2.3, 95% CI [1.1-5.2]), ADL ≤ 5 (OR 1.7, 95% CI [1.1-3.5]), serum albumin levels ≤ 3.5 g/dL (OR 3.4, 95% CI [1.7-6.6]), BMI < 23 kg/m2 (OR 2.5, 95% CI [1.3-4.9]), and hemoglobin levels < 11 g/dL (OR 2.4, 95% CI (1.2-4.7)). With these results, we built a prognostic score. The area under the ROC curve was 0.78 (95% CI, 0.73 to 0.84), and in the validation set, it was 0.73 (95% CI: 0.67-0.79). Conclusions: This simple and highly accurate tool can help physicians making decisions in elderly patients with cancer who are planned to initiate chemotherapy treatment.

Prediction of Unplanned Hospitalizations in Older Patients Treated with Chemotherapy.

PURPOSE: To determine the incidence of unplanned hospitalization (UH) and to identify risk factors for UH in elderly patients with cancer who start chemotherapy. METHODS: In all, 493 patients over 70 years starting new chemotherapy regimens were prospectively included. A pre-chemotherapy geriatric assessment was performed, and tumor and treatment variables were collected. The association between these factors and UH was examined by using multivariable logistic regression. Score points were assigned to each risk factor. RESULTS: During the first 6 months of treatment, 37% of patients had at least one episode of UH. Risk factors were the use of combination chemotherapy at standard doses, a MAX2 index ≥1, a Charlson comorbidity score ≥2, albumin level <3.5 g/dL, falls in the past 6 months ≥1, and weight loss >5%. Three risk groups for UH were established according to the score in all patients: 0-1: 17.5%; 2: 34%; and 3-7: 57% (p < 0.001). The area under receiver operation characteristic (ROC) curve was 0.72 (95% CI: 0.67-0.77). CONCLUSION: This simple tool can help to reduce the incidence of UH in elderly patients with cancer who are scheduled to initiate chemotherapy treatment.

Prediction of Chemotoxicity, Unplanned Hospitalizations and Early Death in Older Patients with Colorectal Cancer Treated with Chemotherapy.

PURPOSE: To identify risk factors for toxicity, unplanned hospitalization (UH) and early death (ED) in older patients with colorectal carcinoma (CRC) initiating chemotherapy. METHODS: 215 patients over 70 years were prospectively included. Geriatric assessment was performed before treatment, and tumor and treatment variables were collected. The association between these factors and grade 3-5 toxicity, UH and ED (<6 months) was examined by using multivariable logistic regression. Score points were assigned to each risk factor. RESULTS: During the first 6 months of treatment, 33% of patients developed grade 3-5 toxicity, 31% had UH and 23% died. Risk factors were, for toxicity, instrumental activities of daily living, creatinine clearance, weight loss and MAX2 index; for UH, Charlson Comorbidity Score, creatinine clearance, weight loss, serum albumin, and metastatic disease; and for ED, basic activities in daily living, weight loss, metastatic disease, and hemoglobin levels. Predictive scores were built with these variables. The areas under receiver operation characteristic (ROC) curves for toxicity, UH and ED were 0.70 (95% CI: 0.64-0.766), 0.726 (95% IC: 0.661-0.799) and 0.74 (95% IC: 0.678-0.809), respectively. CONCLUSION: Simple scores based on geriatric, tumor and laboratory characteristics predict severe toxicity, UH and ED, and may help in treatment planning.

Undertreatment and overtreatment in older patients treated with chemotherapy.

BACKGROUND: Inconsistent doses and schemes are commonly used in older patients receiving cancer chemotherapy. We performed this study in patients with cancer and age ≥ 70 years to determine the frequency of undertreatment and overtreatment as well as factors influencing the decision to modify chemotherapy doses. PATIENTS AND METHODS: Patients aged ≥70 years starting new chemotherapy regimens were prospectively included in a multicentre study. The schedule and drug doses were determined by the treating oncologist. Pre-chemotherapy assessment included sociodemographics, treatment details and geriatric assessment (GA) variables. Association between these factors and undertreatment (use of less intensive cancer treatment [LICT] in a fit patient) or overtreatment (use of standard cancer treatment in an unfit older patient) were examined by multivariate logistic regression. RESULTS: Three- hundred ninety-seven patients were included, 43% of whom received LICT. If not adjusted for GA, toxicity did not differ between those receiving LICT (38%) or standard doses of chemotherapy (37%). If the dose of chemotherapy was analyzed according to the results of GA 61 (15%) patients had been undertreated and 133 (34%) had been overtreated. Undertreatment was related with increasing age and decreased renal function. Factors related with overtreatment were younger age, curative intention of treatment, prescription of G-CSF as primary prophylaxis and adequate cognitive status. Overtreated patients had more grade 3-4 toxicity than those receiving treatment adapted to fragility (42% vs 31%; p < 0.05). CONCLUSIONS: The use of chemotherapy without considering GA leads to overtreatment more commonly than undertreatment in older patients with cancer. Oncologists should take into account the results of GA to stratify patients and to avoid under or overtreatment.

[Impact of antineoplastic drugs on the nutritional status of older patients with cancer. Can the medical oncologist minimize the impact of these drugs on the nutrirional status of these patients?] / Repercusión de los fármacos antineoplásicos sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo médico minimizar el impacto de estos fármacos sobre el estado nutricional del enfermo mayor?

INTRODUCTION: Aging is associated, per se, with the loss of functional reserve of different organs and systems, a greater risk of vulnerability and frailty, sarcopenia and malnutrition, a reality that is extended to cancer patients. There are several factors that are associated with malnutrition in the elderly individual, such as the difficulty in regulating food intake, loss of appetite and anorexia associated with age, alteration of the senses of taste and smell, dysgeusia or economic problems. In the case of the cancer patient, other factors are added to these factors, such as: type of tumor; tumor stage; evolutionary moment of the disease; and baseline situation. Many therapeutic strategies used against the tumor, such as surgery, treatment with radiotherapy (concomitant or not with chemotherapy) and treatment with antitumor drugs influence also the risk of malnutrition. Thus, for example, concomitant chemo-radiation therapy in head and neck tumors, in lung cancer or in pelvic tumors represents a high nutritional risk antitumor therapy. Some of the repercussions of malnutrition in the oncological elderly are severe. Thus, for example, malnutrition in these individuals is associated with: worse survival; increased risk of early discontinuation of chemotherapy treatment; increased risk of chemotherapy toxicity; increased toxicity from other antitumor drugs; and increased risk of mortality during chemotherapy treatment. Taking this information into account, it is essential: to optimize the nutritional status in older patients with cancer prior to starting a systemic antitumor treatment; to carry out a nutritional follow-up throughout the treatment; and to offer early and intense management of malnutrition once it appears, with the purpose of minimizing the impact of antitumor drugs in older patients with cancer. Early management of malnutrition could improve drugs tolerance and increase the health-related quality of life in these patients.

INTRODUCCIÓN: El envejecimiento se asocia a la pérdida de reserva funcional de distintos órganos y sistemas, a un mayor riesgo de vulnerabilidad y de fragilidad, a la sarcopenia y a la malnutrición, realidad que se hace extensible a los pacientes oncológicos. Varios factores se asocian a la malnutrición en el individuo de edad avanzada: dificultad para regular la ingesta de alimentos, pérdida de apetito y anorexia asociadas a la edad, alteración de los sentidos del gusto y olfato, disgeusia o problemas económicos. En el caso del paciente oncológico, a estos factores se añaden otros como: tipo de tumor; estadio tumoral; momento evolutivo de la enfermedad; y situación basal. También las distintas estrategias terapéuticas utilizadas frente al tumor, como cirugía, tratamiento con radioterapia (concomitante o no a quimioterapia) y tratamiento con fármacos antitumorales influyen en el riesgo de malnutrición. Así, por ejemplo, la quimio-radioterapia concomitante en tumores de cabeza y cuello, en cáncer de pulmón o en tumores de localización pélvica, representa una terapia antitumoral de alto riesgo nutricional. Algunas de las repercusiones de la malnutrición en el anciano oncológico son severas. La malnutrición en estos individuos se asocia a: peor supervivencia; mayor riesgo de interrupción precoz del tratamiento con quimioterapia; aumento en el riesgo de toxicidad de la quimioterapia; mayor toxicidad por otros fármacos antitumorales; y riesgo incrementado de mortalidad durante el tratamiento con quimioterapia. Teniendo en cuenta esta información, resulta fundamental optimizar el estado nutricional en el anciano oncológico previo al inicio de un tratamiento antitumoral sistémico, hacer un seguimiento a lo largo del tratamiento y ofrecer un manejo precoz e intenso de la malnutrición una vez aparezca, con la finalidad de minimizar el impacto de los fármacos antitumorales en el anciano, de mejorar la tolerancia de tales fármacos y aumentar la calidad de vida relacionada con la salud en estos pacientes.

Predicting Chemotherapy Toxicity in Older Patients with Cancer: A Multicenter Prospective Study.

BACKGROUND: Standard oncology tools are inadequate to distinguish which older patients are at higher risk of developing chemotherapy-related complications. MATERIALS AND METHODS: Patients over 70 years of age starting new chemotherapy regimens were prospectively included in a multicenter study. A prechemotherapy assessment that included sociodemographics, tumor/treatment variables, and geriatric assessment variables was performed. Association between these factors and the development of grade 3-5 toxicity was examined by using logistic regression. RESULTS: A total of 551 patients were accrued. Chemotherapy doses (odds ratio [OR] 1.834; 95% confidence interval [CI] 1.237-2.719) and creatinine clearance (OR 0.989; 95% CI 0.981-0.997) were the only factors independently associated with toxicity. Only 19% of patients who received reduced doses of chemotherapy and had a creatinine clearance ≥40 mL/minute had grade 3-4 toxicity, compared with 38% of those who received standard doses or had a creatinine clearance <40 mL/minute (p < .0001). However, no satisfactory multivariate model was obtained using different selection approaches. CONCLUSION: Chemotherapy doses and renal function were identified as the major risk factors for developing severe toxicity in the older patient. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up in these patients. IMPLICATIONS FOR PRACTICE: Older patients are more vulnerable to chemotherapy toxicity. However, standard tools are inadequate to identify who is at higher risk of developing chemotherapy-related complications. Chemotherapy doses (standard vs. reduced) and renal function were identified as the major risk factors for developing severe toxicity in the elderly. These factors should be considered when planning to initiate a new chemotherapy regimen and should also lead to a closer follow-up.

Repercusión de los fármacos antineoplásicos sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo médico minimizar el impacto de estos fármacos sobre el estado nutricional del enfermo mayor? / Impact of antineoplastic drugs on the nutritional status of older patients with cancer. Can the medical oncologist minimize the impact of these drugs on the nutrirional status of these patients?

El envejecimiento se asocia, per se, a la pérdida de reserva funcional de distintos órganos y sistemas, a un mayor riesgo de vulnerabilidad y de fragilidad, a la sarcopenia y a la malnutrición, realidad que se hace extensible a los pacientes oncológicos. Son varios los factores que se asocian a la malnutrición en el individuo de edad avanzada, tales como la dificultad para regular la ingesta de alimentos, la pérdida de apetito y la anorexia asociadas a la edad, la alteración de los sentidos del gusto y el olfato, la disgeusia o los problemas económicos. En el caso del paciente oncológico, a estos factores se añaden otros, tales como: a) el tipo de tumor; b) el estadio tumoral; c) el momento evolutivo de la enfermedad; y d) la situación basal. También las distintas estrategias terapéuticas utilizadas frente al tumor, como la cirugía, el tratamiento con radioterapia (concomitante o no a la quimioterapia) y el tratamiento con fármacos antitumorales influyen en el riesgo de malnutrición. Así, por ejemplo, la quimio-radioterapia concomitante en tumores de cabeza y cuello, en cáncer de pulmón o en tumores de localización pélvica, representa una terapia antitumoral de alto riesgo nutricional. Algunas de las repercusiones de la malnutrición en el anciano oncológico son severas. Así, por ejemplo, la malnutrición en estos individuos se asocia a: a) peor supervivencia; b) mayor riesgo de interrupción precoz del tratamiento con quimioterapia; c) aumento en el riesgo de toxicidad de la quimioterapia; d) mayor toxicidad por otros fármacos antitumorales; y e) riesgo incrementado de mortalidad durante el tratamiento con quimioterapia. Teniendo en cuenta esta información, resulta fundamental optimizar el estado nutricional en el anciano oncológico previo al inicio de un tratamiento antitumoral sistémico, hacer un seguimiento nutricional a lo largo de dicho tratamiento y ofrecer un manejo precoz e intenso de la malnutrición una vez que aparezca esta, con la finalidad de minimizar el impacto de los fármacos antitumorales en el anciano oncológico, de mejorar la tolerancia de tales fármacos y de aumentar la calidad de vida relacionada con la salud en estos pacientes. Dichos aspectos son los que se tratan en profundidad en este artículo

Aging is associated, per se, with the loss of functional reserve of different organs and systems, a greater risk of vulnerability and frailty, sarcopenia and malnutrition, a reality that is extended to cancer patients. There are several factors that are associated with malnutrition in the elderly individual, such as the difficulty in regulating food intake, loss of appetite and anorexia associated with age, alteration of the senses of taste and smell, dysgeusia or economic problems. In the case of the cancer patient, other factors are added to these factors, such as: a) type of tumor; b) tumor stage; c) evolutionary moment of the disease; and d) baseline situation. Many therapeutic strategies used against the tumor, such as surgery, treatment with radiotherapy (concomitant or not with chemotherapy) and treatment with antitumor drugs influence also the risk of malnutrition. Thus, for example, concomitant chemo-radiation therapy in head and neck tumors, in lung cancer or in pelvic tumors represents a high nutritional risk antitumor therapy. Some of the repercussions of malnutrition in the oncological elderly are severe. Thus, for example, malnutrition in these individuals is associated with: a) worse survival; b) increased risk of early discontinuation of chemotherapy treatment; c) increased risk of chemotherapy toxicity; d) increased toxicity from other antitumor drugs; and e) increased risk of mortality during chemotherapy treatment. Taking this information into account, it is essential: a) to optimize the nutritional status in older patients with cancer prior to starting a systemic antitumor treatment; b) to carry out a nutritional follow-up throughout the treatment; and c) to offer early and intense management of malnutrition once it appears, with the purpose of minimizing the impact of antitumor drugs in older patients with cancer. Early management of malnutrition could improve drugs tolerance and increase the health-related quality of life in these patients. All these aspects are discussed in depth in this article

Epigenetic Deregulation of Protocadherin PCDHGC3 in Pheochromocytomas/Paragangliomas Associated With SDHB Mutations.

CONTEXT: SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but ∼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed. OBJECTIVE: This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs. DESIGN: We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs. RESULTS: We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion. CONCLUSIONS: Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.

[Integral approach to the older patient with cancer]. / El abordaje integral del paciente oncológico de edad avanzada.

INTRODUCTION: The world population, as well as the number of elderly people, grow exponentially. Elderly individuals are at a higher risk of developing an oncological disease, especially because they are subject to a longer period of exposure to carcinogens, and a worse capacity for regeneration of their deoxyribonucleic acid (DNA) (1). Cancer in elderly individuals represents 80% of the annual deaths secondary to this pathology (2). The older patient with cancer presents many differences with respect to the rest of elderly individuals. On the one hand, functional limitation and geriatric syndromes are more prevalent (3), as well as the presence of frailty (4). In addition, they habitually have a worse perception of their health status (4). For all these reasons, the attention to oncological older patients must be specialized and, in their evaluation, the use of a fundamental tool is required, the Comprehensive Geriatric Assessment (CGA). As its name indicates, its application requires collaboration between different specialties (5,6). This multidisciplinary work will improve the baseline situation of the patient, in those cases in which it is possible, and will facilitate the subsequent therapeutic management (7). Finally, the existence of concrete organizational models, such as the Oncogeriatrics Units, or the Cancer Consultations in the Elderly, can facilitate and favor this integral approach (5). In this article a review of all these concepts is carried out.

INTRODUCCIÓN: La población mundial, así como el número de personas de edad avanzada, crecen exponencialmente. Los individuos ancianos tienen más riesgo de desarrollar una enfermedad oncológica debido, sobre todo, a que están sometidos a un periodo de exposición a carcinógenos más prolongado y por una peor capacidad de regeneración de su ácido desoxirribonucleico (ADN) (1). El cáncer en individuos de edad avanzada representa el 80% de los fallecimientos anuales secundarios a esta patología (2). El anciano oncológico presenta una serie de diferencias con respecto al resto de individuos de edad avanzada. Por un lado, son más prevalentes la limitación funcional y los síndromes geriátricos (3), así como la presencia de fragilidad (4); además, habitualmente tienen una peor percepción de su estado de salud (4). Por todos estos motivos, la atención al anciano oncológico debe ser especializada, y en su evaluación se requiere el uso de una herramienta fundamental, la valoración geriátrica integral (VGI), que, como su nombre indica, para su aplicación requiere de la colaboración entre distintas especialidades (5,6). Este trabajo multidisciplinar permitirá mejorar la situación basal del paciente en aquellos casos en los que sea posible y facilitará que el manejo terapéutico posterior sea idóneo (7). Por último, la existencia de modelos organizativos concretos, tales como las unidades de oncogeriatría o las consultas de cáncer en el anciano, pueden facilitar y favorecer dicho abordaje integral (5). En este artículo se lleva a cabo una revisión de todos estos conceptos.

¿Cuál es el papel de la valoración geriátrica integral en Oncogeriatría? / What is the role of the comprehensive geriatric assessment in Geriatric Oncology?

El aumento creciente de la población mundial y el envejecimiento generalizado se han acompañado de un incremento en la prevalencia de cáncer en el anciano. El envejecimiento se asocia a determinados cambios fisiológicos, algunos de los cuales se potencian por la propia neoplasia. Junto a esto, el anciano oncológico suele tener más problemas que el resto de los individuos de edad avanzada, y es habitual que presente multitud de déficits. Estas características hacen necesario un manejo especial del mismo, utilizando, para ello, la principal herramienta empleada en Geriatría, la valoración geriátrica integral. Con este manuscrito se pretende analizar cuál es la trascendencia de la valoración geriátrica integral en dicho grupo poblacional, prestando especial atención a su capacidad para predecir la toxicidad a la quimioterapia y la supervivencia del anciano oncológico, y su capacidad para clasificar a estos pacientes en grupos que faciliten la toma de decisiones posterior

The growing increase in world population and generalised aging have been accompanied by an increase in the prevalence of cancer in the elderly. Aging is associated with certain physiological changes, some of which are enhanced by the neoplasm itself. Along with this, the elderly oncology patient usually has more problems than the rest of the elderly, and has a multitude of deficits. These characteristics require a special handling of the older patient with cancer, by using the main tool used in Geriatrics, the comprehensive geriatric assessment. This article analyses the importance of the comprehensive geriatric assessment in this population group, paying special attention to its ability to predict the toxicity of chemotherapy and the survival of the elderly oncology, as well as its ability to classify these patients into groups that help in the decision making process

[What is the role of the comprehensive geriatric assessment in Geriatric Oncology?] / ¿Cuál es el papel de la valoración geriátrica integral en Oncogeriatría?

The growing increase in world population and generalised aging have been accompanied by an increase in the prevalence of cancer in the elderly. Aging is associated with certain physiological changes, some of which are enhanced by the neoplasm itself. Along with this, the elderly oncology patient usually has more problems than the rest of the elderly, and has a multitude of deficits. These characteristics require a special handling of the older patient with cancer, by using the main tool used in Geriatrics, the comprehensive geriatric assessment. This article analyses the importance of the comprehensive geriatric assessment in this population group, paying special attention to its ability to predict the toxicity of chemotherapy and the survival of the elderly oncology, as well as its ability to classify these patients into groups that help in the decision making process.

Clinical significance and peculiarities of succinate dehydrogenase B and hypoxia inducible factor 1α expression in parasympathetic versus sympathetic paragangliomas.

BACKGROUND: Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1α (HIF-1α) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1α proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. METHODS: The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1α immunohistochemistry analysis was performed in 158 genetically defined patients. RESULTS: Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1α stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1α positive cells. CONCLUSION: As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1α stabilization in HNPGLs, this is not a clinically useful biomarker.

El abordaje integral del paciente oncológico de edad avanzada / Integral approach to the older patient with cancer

La población mundial, así como el número de personas de edad avanzada, crecen exponencialmente. Los individuos ancianos tienen más riesgo de desarrollar una enfermedad oncológica debido, sobre todo, a que están sometidos a un periodo de exposición a carcinógenos más prolongado y por una peor capacidad de regeneración de su ácido desoxirribonucleico (ADN) (1). El cáncer en individuos de edad avanzada representa el 80% de los fallecimientos anuales secundarios a esta patología (2). El anciano oncológico presenta una serie de diferencias con respecto al resto de individuos de edad avanzada. Por un lado, son más prevalentes la limitación funcional y los síndromes geriátricos (3), así como la presencia de fragilidad (4); además, habitualmente tienen una peor percepción de su estado de salud (4). Por todos estos motivos, la atención al anciano oncológico debe ser especializada, y en su evaluación se requiere el uso de una herramienta fundamental, la valoración geriátrica integral (VGI), que, como su nombre indica, para su aplicación requiere de la colaboración entre distintas especialidades (5,6). Este trabajo multidisciplinar permitirá mejorar la situación basal del paciente en aquellos casos en los que sea posible y facilitará que el manejo terapéutico posterior sea idóneo (7). Por último, la existencia de modelos organizativos concretos, tales como las unidades de oncogeriatría o las consultas de cáncer en el anciano, pueden facilitar y favorecer dicho abordaje integral (5). En este artículo se lleva a cabo una revisión de todos estos conceptos

The world population, as well as the number of elderly people, grow exponentially. Elderly individuals are at a higher risk of developing an oncological disease, especially because they are subject to a longer period of exposure to carcinogens, and a worse capacity for regeneration of their deoxyribonucleic acid (DNA) (1). Cancer in elderly individuals represents 80% of the annual deaths secondary to this pathology (2). The older patient with cancer presents many differences with respect to the rest of elderly individuals. On the one hand, functional limitation and geriatric syndromes are more prevalent (3), as well as the presence of frailty (4). In addition, they habitually have a worse perception of their health status (4). For all these reasons, the attention to oncological older patients must be specialized and, in their evaluation, the use of a fundamental tool is required, the Comprehensive Geriatric Assessment (CGA). As its name indicates, its application requires collaboration between different specialties (5,6). This multidisciplinary work will improve the baseline situation of the patient, in those cases in which it is possible, and will facilitate the subsequent therapeutic management (7). Finally, the existence of concrete organizational models, such as the Oncogeriatrics Units, or the Cancer Consultations in the Elderly, can facilitate and favor this integral approach (5). In this article a review of all these concepts is carried out

Experience with eribulin in HR+/HER2- metastatic breast cancer, including a male.

Numerous patient- and disease-related factors must be considered when deciding a treatment approach for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer. Hormone therapy (HT) is generally the first option in the absence of compelling reasons for chemotherapy (e.g., rapidly progressive visceral disease). After failure of first-choice HT, alternative HT options are usually attempted until hormone resistance occurs and chemotherapy becomes the treatment of choice. The first two patients presented herein experienced prolonged disease control with third-line eribulin after two lines of HT. The third report involves a case of male breast cancer which typically presents as the HR+/HER2- phenotype. Eribulin in the second line provided prolonged clinical improvement and was well tolerated.

Delphi consensus of an expert committee in oncogeriatrics regarding comprehensive geriatric assessment in seniors with cancer in Spain.

OBJECTIVES: The aim of this work was to reach a national consensus in Spain regarding the Comprehensive Geriatric Assessment (CGA) domains in older oncological patients and the CGA scales to be used as a foundation for widespread use. MATERIAL AND METHODS: The Delphi method was implemented to attain consensus. Representatives of the panel were chosen from among the members of the Oncogeriatric Working Group of the Spanish Society of Medical Oncology (SEOM). Consensus was defined as ≥66.7% coincidence in responses and by the stability of said coincidence (changes ≤15% between rounds). The study was conducted between July and December 2016. RESULTS: Of the 17 people invited to participate, 16 agreed. The panel concluded by consensus that the following domains should be included in the CGA:(and the scales to evaluate them): functional (Barthel Index, Lawton-Brody scale, gait speed), cognitive (Pfeiffer questionnaire), nutritional (Mini Nutritional Assessment - MNA), psychological/mood (Yesavage scale), social-familial (Gijon scale), comorbidity (Charlson index), medications, and geriatric syndromes (urinary and/or fecal incontinence, low auditory and/or visual acuity, presence of falls, pressure sores, insomnia, and abuse). Also by consensus, the CGA should be administered to older patients with cancer for whom there is a subsequent therapeutic intent and who scored positive on a previous frailty-screening questionnaire. CONCLUSION: After 3 rounds, consensus was reached regarding CGA domains to be used in older patients with cancer, the scales to be administered for each of these domains, as well as the timeline to be followed during consultation.

Detección y evaluación del papel de la sarcopenia en ancianos con cáncer tratados con quimioterapia. Proyecto ONCOSARCO / Detection and evaluation of the role of sarcopenia in elderly patients with cancer treated with chemotherapy. ONCOSARCO project

Objetivos. Objetivos principales: elaborar un modelo predictor de toxicidad a la quimioterapia en ancianos oncológicos, a partir de variables relacionadas con la sarcopenia; identificar cuál de estos parámetros, sarcopenia o fragilidad, es el mejor predictor de toxicidad de la quimioterapia en ancianos. Material y métodos. Estudio prospectivo observacional, con pacientes ≥70 años tratados con quimioterapia en la Unidad de Cáncer en el Anciano de la Sección de Oncología Médica del Hospital Virgen de la Luz de Cuenca. Antes del inicio de la quimioterapia, a cada paciente se le determinará la fuerza muscular (handgrip, fuerza cilíndrica manual, fuerza de presión pulgar, flexión de cadera, extensión de rodilla), la masa muscular (índice de masa muscular esquelética) y la función física (velocidad 5 metros y test 5-Sit to stand). A lo largo de los 4 meses de tratamiento con quimioterapia, se recogerá la aparición de toxicidad severa. Se evaluará, mediante un primer análisis de regresión logística multinomial, cuál de ellos, sarcopenia (definición del European Working Group on Sarcopenia in Older People o fragilidad (criterios propuestos por Fried et al.), es el mejor predictor de toxicidad de la quimioterapia. Mediante un segundo análisis de regresión se pretende crear el primer modelo de predicción de toxicidad a la quimioterapia en el anciano oncológico, basado en la definición de sarcopenia. Conclusiones. Se espera que del análisis definitivo de este proyecto puedan encontrarse factores predictores de toxicidad a quimioterapia en ancianos oncológicos (AU)

Objectives. To develop a predictive model of toxicity to chemotherapy in elderly patients with cancer, using the variables associated with sarcopenia, and to identify which of these parameters, sarcopenia or frailty, is the best predictor of toxicity to chemotherapy in the elderly. Material and methods. A prospective observational study with patients ≥70 years treated with chemotherapy in the Cancer Unit for the Elderly, in the Medical Oncology Section of the Hospital Virgen de la Luz de Cuenca. The following tests will be performed by each patient before chemotherapy: muscle strength (handgrip, cylindrical handgrip, pinch gauge, hip flexion, knee extension), muscle mass (skeletal muscle mass index), and physical function (gait speed and 5STS test). The occurrence of severe toxicity will be recorded over a period of 4 months of chemotherapy treatment. It will be evaluated, using logistic regression analysis, whether sarcopenia (defined by the European Working Group on Sarcopenia in Older People) or frailty (defined by the phenotype of frailty) is the best predictor of chemotherapy toxicity. Using a multinomial logistic regression analysis, we will try to create the first model to predict toxicity to chemotherapy in elderly patients with diagnosis of cancer, based on the definition of sarcopenia. Conclusions. It is expected that the final analysis of this project will be useful to detect predictive factors of toxicity to chemotherapy in elderly patients with cancer (AU)