Management of the toxicity of chemotherapy and targeted therapies in elderly cancer patients.

The elderly form a very heterogeneous group in relation to their general health state, degree of dependence, comorbidities, performance status, physical reserve and geriatric situation, so cancer treatment in the older patient remains a therapeutic challenge. The physiological changes associated with aging increase the risk of developing a serious toxicity induced by chemotherapy treatment, as well as other undesirable consequences as hospitalizations, dependence and non-compliance with treatment, that can negatively affect survival, quality of life and treatment efficacy. The use of hematopoietic growth factors and other active supportive interventions in the elderly can help prevent and/or alleviate these toxicities. However, we have little data on the efficacy and tolerance of support treatments in the older patient. The objective of this work is to review the most frequent toxicities of oncological treatments in the elderly and their management.

Can we avoid the toxicity of chemotherapy in elderly cancer patients?

Although approximately 50% of cancer patients are 70 years of age or older, cancer treatment in the elderly remains a therapeutic challenge. The elderly form a very heterogeneous group in relation to their general health state, degree of dependence, comorbidities, performance status, physical reserve and geriatric situation, for which therapeutic decisions must be made in an individualized manner. In addition, changes in pharmacokinetics and pharmacodynamics of the drugs occur with age, as well as the tolerance of the tissues, leading to a narrowing of the therapeutic margin and an increase in toxicity. In the general population, Performace Status (PS) has traditionally been used to estimate tolerance to chemotherapy, but in the elderly population it is not useful. In this review we summarize the current knowledge about the pharmacology of antineoplastic drugs in the elderly and the tools available to help us identify risk of chemotherapy toxicity in these patients.

General recommendations paper on the management of older patients with cancer: the SEOM geriatric oncology task force's position statement.

Population aging is associated with greater numbers of older people with cancer. Thanks to treatment advances, not only are more seniors diagnosed with cancer, but there are also more and more older cancer survivors. This upward trend will continue. Given the heterogeneity of aging, managing older patients with cancer poses a significant challenge for Medical Oncology. In Spain, a Geriatric Oncology Task Force has been set up within the framework of the Spanish Society for Medical Oncology (SEOM). With the aim of generating evidence and raising awareness, as well as helping medical oncologists in their training with respect to seniors with cancer, we have put together a series of basic management recommendations for this population. Many of the patients who are assessed in routine clinical practice in Oncology are older. CGA is the basic tool by means of which to evaluate older people with cancer and to understand their needs. Training and the correct use of recommendations regarding treatment for comorbidities and geriatric syndromes, support care, and drug-drug interactions and toxicities, including those of antineoplastic agents, as detailed in this article, will ensure that this population is properly managed.

Geriatric oncology in Spain: survey results and analysis of the current situation.

INTRODUCTION: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. OBJECTIVES: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. METHODS: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. RESULTS: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. CONCLUSIONS: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived.

Oral chemotherapy in elderly women with metastatic breast cancer.

Life expectancy has significantly increased over the past 30 years, with a greater prevalence of diverse disease states, especially cancer. As older persons are a very heterogeneous group with an increased prevalence of comorbidities and a relative inability to tolerate the adverse effects of chemotherapy, the treatment of cancer in the elderly is particularly demanding. The principles of its management are similar to those in younger patients but with special considerations linked to comorbidities and clinical status. The objective of chemotherapeutic treatment in metastatic breast cancer has historically been primarily palliative. The introduction of newer approaches with improved or at least equivalent efficacy and reduced toxicity is highly desirable. Such approaches may include the use of less toxic drugs, more convenient routes of administration (e.g., oral) and home-based (outpatient) rather than hospital-based therapies. The available oral cytostatic drugs include vinorelbine and capecitabine. In this review, we analyze oral cytostatic drugs in the elderly patient diagnosed with metastatic breast cancer.

Tools for decision-making in older cancer patients. Role of the comprehensive geriatric assessment.

Approximately 60% of cancer incidence and 70% of cancer mortality occurs in individuals older than 65 years. The optimal approach to cancer therapy in older adults is often unclear. Historically, advanced age has been an exclusion criterion in clinical cancer trials, and older adults have been consistently underrepresented. As a result, there is a lack of information about treatment efficacy and tolerability in this population. Comprehensive Geriatric Assessment (CGA) is one of the most useful tools for the oncologist to make decisions related to older patients diagnosed with cancer. This tool has proved to be very useful to detect many deficits, tolerance to chemotherapy and survival in such patients. In this review, we analyze the role of CGA in decision making in geriatric oncology.

Targeted anti-HER2 cancer therapy in elderly women diagnosed with breast cancer.

Trastuzumab or lapatinib treatment with chemotherapy or hormonotherapy are the gold standard treatments for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (early breast cancer or metastatic breast cancer). Older patients have been largely underrepresented in clinical trials, and few data on trastuzumab or lapatinib efficacy and toxicity have been reported for this subgroup. This article has reviewed the main articles that have analyzed these items.

Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain.

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit.

18F-FDG semi-quantitative parameters and biological prognostic factors in locally advanced breast cancer.

AIM: To analyse the correlation between (18)F-FDG uptake assessed by PET/CT in locally advanced breast tumours and histopathological and immunohistochemical prognostic factors. MATERIAL AND METHODS: Thirty-six women with breast cancer were prospectively evaluated. PET/CT was requested in the initial staging previous to adjuvant chemotherapy (multicentric study). All the patients underwent an (18)F-FDG PET/CT with a dual-time-point acquisition. Both examinations were evaluated qualitatively and semiquantitatively with calculation of SUVmax values in PET-1 (SUV-1) and in PET-2 (SUV-2) and the percentage variation of the standard uptake values (retention index) between PET-1 and PET-2. Clinical and metabolic stages were assessed according to TNM classification. The biological prognostic parameters, such as the steroid receptor status, p53 and c-erbB-2 expression, proliferation rate (Ki-67), and grading were determined from tissue of the primary tumour. Metabolic and biological parameters were correlated. RESULTS: A positive relationship was found between semiquantitative metabolic parameters and biological parameters. SUV-1 and SUV-2 values did not show significant statistical correlation (p<.05) except for the clinical tumour size. About the biological parameters, retention index showed the best results with positive and significant relation (p<.05) with estrogen and progesterone receptor status and Ki-67. Isolated SUV values did not show significant relation to these parameters. CONCLUSION: Retention index showed the best relation with biological parameters compared to isolated SUVmax values. These data suggest that SUV change over time is a prognostic marker.

Extranodal rosai-dorfman disease with cutaneous and periodontal involvement: a rare presentation.

Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai-Dorfman disease (RDD) was first described as a distinct clinicopathological entity by Rosai and Dorfman in 1969. SHML is commonly characterized by painless cervical lymphadenopathy, and its clinical course is generally benign and self-limiting. This disorder commonly involves the lymph nodes but may secondarily involve the skin. However, purely cutaneous disease without lymphadenopathy or internal organ involvement rarely occurs. In the absence of the massive lymphadenopathy that is characteristic of RDD, the diagnosis of purely cutaneous RDD may be complicated by the rare, nonspecific clinical appearance of skin lesions and the broad histopathological differential diagnosis of this disorder. A high level of suspicion of this disease on the part of the clinician or pathologist is often required. We present a case of cutaneous RDD associated with involvement of periodontal tissue.

Muscle metastasis of carcinoma

Metastatic carcinoma of the soft tissue is extremely rare compared with bone metastases. An intramuscular mass is often thought to be a primary soft tissue sarcoma because intramuscular metastases are very uncommon. Any painful soft tissue mass occurring in patients with a known history of carcinoma, particularly with extensive peritumoral enhancement associated with central necrosis, is highly suspicious for skeletal muscle metastasis. A needle biopsy is necessary for proper diagnosis. It is very important to make a differential diagnosis between metastasis and primary cancer in these cases. Here we present a review of known evidence (AU)

Development of a cancer-specific Comprehensive Geriatric Assessment in a University Hospital in Spain.

INTRODUCTION: The Comprehensive Geriatric Assessment (CGA) is a key component of the treatment approach for older cancer patients. The goals of the current study were to develop a brief but non-self-administered cancer-specific geriatric assessment and to determine its feasibility, as measured by (1) the length of time to completion and (2) patient satisfaction. METHODS: The literature was reviewed to select validated scales for geriatric assessment across the following domains: functional status, co-morbidity, cognition, social support and risk of malnutrition. Oncologic patients older than 70 years were included in the study. RESULTS: The instrument was completed by 99 patients (mean age, 78.65 yrs). The mean time to completion of that was 12.9 min (range, 9.5-20.5 min). Most patients were satisfied with its length (63.6%), and most considered it fairly easy to complete (69.7%). CONCLUSIONS: The designed CGA was accepted by most patients and was not perceived to be overly time-consuming.

Comparison of two frailty screening tools in older women with early breast cancer.

INTRODUCTION AND OBJECTIVES: We have tested two frailty screening tools (the Barber Questionnaire [BQ] and the Vulnerable Elderly Survey [VES-13]) to select patients who may benefit from Comprehensive Geriatric Assessment (CGA). MATERIALS AND METHODS: We included women ≥ 65 years old, diagnosed with early breast cancer at the University General Hospital in Elche. We compared impairment in the BQ score (score <0 vs. > 0) and impairment in the VES-13 score (<3 vs. ≥ 3), with impaired CGA results (< 2 scales with deficits vs. ≥2). We evaluated the diagnostic performance of both questionnaires by Area Under Curve [AUC] and analyzed their concordance with CGA scales (intraclass correlation coefficient [ICC]). RESULTS: Forty-one women were included. The risk of frailty was 41.76%, 29.3%, and 55.7% when evaluated with BQ, VES-13 and CGA, respectively. The correlation between BQ and CGA was fair (ICC=0.672), but between VES-13 and CGA was very good (ICC=0.814). The predictive capacity of the BQ and the VES-13 for detecting frailty risk was intermediate (AUC=0.719) and high (AUC=0.876), respectively. CONCLUSIONS: We propose the use of the VES-13 in older women with early breast cancer and the implementation of CGA when VES-13<3.

Biallelic MYH germline mutations as cause of Muir-Torre syndrome.

Muir-Torre syndrome is a rare, inherited disease predisposing of gastrointestinal and cutaneous tumours, such as keratoacanthomas and sebaceous gland adenomas. Muir-Torre syndrome is usually inherited in an autosomal dominant fashion and associated with mutations in the mismatch repair genes, predominantly in MLH1 and MSH2 genes. This report describes a man who has multiple adenomatous colon polyps, a gastric cancer, multiple colorectal cancers and sebaceous adenomas caused by biallelic MYH germline mutations. This finding demonstrates that MYH gene analysis should be considered in Muir-Torre families where no mismatch repair gene mutations have been found. Furthermore, this report contributes to characterize the clinical phenotype caused by biallelic mutations in MYH gene, which may share with other hereditary colon cancer syndromes.

[Systemic mastocytosis: systematic review]. / Mastocitosis sistémica: Revisión sistemática.

Mastocytosis is a hematologic malignance characterized by an abnormal proliferation of mastocytes. In a consensus classification in 2001, it was distinguished between matters limited to skin and systemic matters (70% of osseous involvement and 50% of hepatomegaly). The most typical symptoms are skin lesions and systemic manifestations due to mediators secreted by tumoral cells. They are useful chemotherapy to reduce the tumoral burden and antihistaminic to control systemic manifestations. Interferon is useful in most of systemic and local manifestations, and it is recommended to use prednisona before the use of this medication.