Exercise and cancer: a position statement from the Spanish Society of Medical Oncology.

Due to improvements in the number of cancer survivors and survival time, there is a growing interest in healthy behaviors, such as physical activity (PA), and their potential impact on cancer- and non-cancer-related morbidity in individuals with cancer. Commissioned by the Spanish Society of Medical Oncology (SEOM), in this review, we sought to distill the most recent evidence on this topic, focusing on the mechanisms that underpin the effects of PA on cancer, the role of PA in cancer prevention and in the prognosis of cancer and practical recommendations for clinicians regarding PA counseling. Despite the available information, the introduction of exercise programs into the global management of cancer patients remains a challenge with several areas of uncertainty. Among others, the most effective behavioral interventions to achieve long-term changes in a patient's lifestyle and the optimal intensity and duration of PA should be defined with more precision in future studies.

SEOM clinical guidelines in advanced and recurrent breast cancer (2018).

Although the metastasic breast cancer is still an incurable disease, recent advances have increased significantly the time to progression and the overall survival. However, too much information has been produced in the last 2 years, so a well-based guideline is a valuable document in treatment decision making. The SEOM guidelines are intended to make evidence-based recommendations on how to manage patients with advanced and recurrent breast cancer to achieve the best patient outcomes based on a rational use of the currently available therapies. To assign a level of certainty and a grade of recommendation the United States Preventive Services Task Force guidelines methodology was selected as reference.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours.

PURPOSE: To estimate the cost per skeletal-related event (SRE) in patients with bone metastases secondary to solid tumours in the Spanish healthcare setting. METHODS: Patients diagnosed with bone metastases secondary to breast, prostate or lung cancer were included in this multicentre, observational study. SREs are defined as pathologic fracture (vertebral and non-vertebral fracture), radiation to bone, spinal cord compression or surgery to bone. Health resource utilisation associated with these events (inpatient stays, outpatient, emergency room and home health visits, nursing home stays and procedures) were collected retrospectively for all SREs that occurred in the 97 days prior to enrolment and prospectively during follow-up. Unit costs were obtained from the 2010 eSalud healthcare costs database. RESULTS: A total of 93 Spanish patients with solid tumours were included (31 had breast cancer, 21 prostate cancer and 41 lung cancer), contributing a total of 143 SREs to this cost analysis. Inpatient stays (between 9.0 and 29.9 days of mean length of stay per inpatient stay by SRE type) and outpatient visits (between 1.7 and 6.4 mean visits per SRE type) were the most frequently reported types of health resources utilised. The mean cost per SRE was between 2,377.79 (radiation to bone) and 7,902.62 (spinal cord compression). CONCLUSION: SREs are associated with a significant consumption of healthcare resources that generate a substantial economic burden for the Spanish healthcare system.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer.

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered (AU)

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[The clinico-mammographic follow-up of breast cancer after conservative treatment]. / Seguimiento clínico-mamográfico del cáncer de mama tras tratamiento conservador.

Clinical and mammographic follow-up of 149 patients diagnosed of stage I and II breast neoplasm and treated with conservative surgery and irradiation between January 1986 and December 1988 was reviewed to determine clinical and radiographic recurrence pattern. Follow-up controls included a clinical examination and a mammogram at 6-9 months, a second at 10-16, a third at 17-22, a fourth at 23-24 and a mammogram yearly and a clinical examination every 6 months thereafter. To December 1991 18 patients recurred. 12 had a metastatic spread, 3 a unique local recurrence and 3 a local recurrence with a metastasis spread. Clinical recurrence was as a carcinomatous mastitis in three patients and a solid nodule in two. Radiologic recurrence was as an augmented skin thickness in three patients. Mammogram was not performed in one patient because an associated poor prognostic metastatic spread. Mammographic skin thickness secondary to irradiation appeared in 93% of the patients at 6-9 first control, 62% at second, 50% at third and 35% at fourth. The number of recurrences is scarce to achieve any clinical, pathological or treatment factor associated with greater risk of recurrence. We suggest that first mammogram should be delayed after 12 months of treatment because we would not obtain any relevant clinical information before, once observed skin thickness persistence at 6 months and most frequent recurrence radiologic pattern.

[Follow-up of patients with localized germinal testicular tumors: 6 years' experience at the "Santa Creu i Sant Pau" Hospital]. / Seguimiento en pacientes con tumores germinales de testículo localizado: seis años de experiencia del Hospital de la "Santa Creu i Sant Pau".

From 1984 to 1989, 89 patients with stage I testicular carcinoma had been treated and followed at the Oncology Unit of the "Santa Creu i Sant Pau" Hospital. The histologic diagnosis was that of seminoma in 53 and nonseminomatous tumor in 36 patients. Treatment considered of inguinal orchidectomy and close clinical surveillance. Eight of the patients that had been diagnosed as having seminoma received adjuvant radiotherapy since follow-up could not be possible. Recurrence was observed in 5 of the 45 (11 por 100) patients with seminoma and 11 of the 36 (31 por 100) with nonseminomatous tumor that could be followed. All recurrences received chemotherapy (cisplatin and etoposide) which achieved complete remission. All of the patients are currently tumor-free after a mean follow-up of 34 months for the patients with seminoma, 39 months for those with nonseminomatous tumor and no recurrence, and 20 months for the nonseminomatous tumors that had recurred. Surveillance following orchidectomy for stage I testicular tumors is a valid approach if the patient can be followed correctly and achieves the same results as other more aggressive therapeutic strategies.

Intensive chemotherapy in poor-prognosis nonseminomatous germ cell tumors of the testis.

Forty-one patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) of the testis were treated between 1980 and 1989. This group was defined by the presence of one of the following features: multiple large lung metastases, bone, liver or brain metastases, abdominal mass greater than 10 cm, abdominal mass greater than 5 cm with high serum concentration of the tumor markers [alpha-fetoprotein (alpha FP) greater than 500 kU/l or beta-subunit of human chorionic gonadotropin (beta HCG) greater than 1,000 IU/l) or very high serum tumor marker concentrations (alpha FP greater than 5,000 kU/l or beta HCG greater than 10,000 IU/l). The first 21 patients were treated with cisplatin, vinblastine, bleomycin (PVB) chemotherapy and the following 20 with an intense, alternating 6-drug chemotherapy consisting of cisplatin, bleomycin, vincristine, methotrexate, etoposide and ifosfamide (BOMP/EPI). Surgery of residual masses was performed when tumor markers were negative. Fifteen patients (71.4%) in the PVB group and 18 patients (85%) in the BOMP/EPI group remained disease-free at a median follow-up of 67 and 41 months, respectively. None of the resected masses in the BOMP/EPI group contained malignant disease whereas viable carcinoma was found in 5 of 14 (26.4%) patients in the PVB group. The toxicity of the BOMP/EPI regimen was severe but tolerable. Intensive chemotherapy regimen seems to be useful in this subset of patients, but randomised prospective trials comparing these with standard chemotherapy are necessary.

[Does total androgen suppression in advanced prostatic cancer induce a greater number of complete remissions? A phase II trial]. / Induce la supresión androgénica total en cáncer de próstata avanzado mayor no. de remisiones completas? Un ensayo en fase II.

The present Phase II study's main objective was to evaluate the rate of complete responses (CR) obtained through total androgenic suppression (TAS) in patients with disseminated prostate carcinoma. Twenty consecutive patients were recruited of which 19 were evaluable for response and toxicity. Treatment consisted in an association of orchiectomy or the analogous LH-RH Buselerin with the antiandrogenic Flutamide. There was 1 CR (5%) and 17 partial responses (PR). Sixteen patients with symptomatic disease had subjective improvement, usually during the first month of treatment. After an average follow-up of 20 months (range 7-29), 1 patient remains CR and 7 have regressed following PR, 4 of which have died. Tolerance was good, and side effects secondary to hypoandrogenism were frequent, although mild, requiring treatment discontinuation in 1 case. It is concluded that TAS is an excellent palliative approach in disseminated prostate carcinoma though the rate of CRs obtained is sensibly lower to that reported by Labrie (28.3%) and in the range of 0-8% achieved in most studies. It is questionable whether it will become standard therapy for metastatic prostate carcinoma.