Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Evaluation of waiting times for breast cancer diagnosis and surgical treatment.

PURPOSE: To analyse any delays in breast cancer diagnosis and surgical treatment, influence of clinical and biological factors and influence of delays on survival. METHODS/PATIENTS: A descriptive, observational, and retrospective study was conducted between 2006 and 2016 on stages I-III breast cancer patients. This is a retrospective review of health records to collect data on delays, patients' clinical data, biological features of the tumour and information on treatment. Mortality data from the National Death Index. RESULTS: In 493 evaluable patients, the median of days from the first symptom to mammography, biopsy, and surgery was 41, 57, and 92, respectively. The median of days from screening mammography to biopsy and surgery was 10 and 51, respectively. From biopsy to surgery, the median was 34 days in every case. Over the last 5 years, an increase in biopsy-surgery delay has been observed (p = 0.0001). Tumour stages I and II vs. stage III (RR 1.74. 95% CI 1.08-2.80, p = 0.027), diagnosis in screening (RR 0.66. 95% CI 0.45-0.96, p = 0.030), and use of magnetic resonance imaging (RR 2.08. 95 CI 1.21-3.56, p = 0.008) condition a greater biopsy-surgery delay. No influence of delays on survival has been identified. CONCLUSIONS: Delays in diagnosis and surgery in the case of women diagnosed on the basis of symptoms may be improved. There is a temporary tendency to a greater delay in surgery. Some clinical and biological factors must be taken into account to optimise delays. Survival results are not adversely affected by delays.

[Influence of clinical and biographical factors on the quality of life of women with breast cancer receiving adjuvant chemotherapy]. / Influencia de los factores clínicos y biográficos en la calidad de vida de las mujeres durante la quimioterapia adyuvante por cáncer de mama.

OBJECTIVE: Adjuvant chemotherapy affects the life of women with breast cancer in different ways. The aim of this work is to study the effect of adjuvant chemotherapy on the quality of their lives and the impact of their clinical and biographical characteristics. PATIENTS AND METHOD: Women with breast cancer, candidates for adjuvant chemotherapy, participating in a randomised trial with non-pharmacological intervention (ClinicalTrials.gov Identifier: NCT00964522), completed the EORTC QOL-C30 and QOL-BR23 quality of life questionnaires before, in the middle, and at the end of the treatment. RESULTS: Fifty women completed the questionnaires. Overall health got worse over time (p=0.01). Physical functioning (p=0.0001) and body image (p=0.002) were the scales that deteriorated most, and asthenia (p=0.004), nausea/vomiting (p=0.05), and anorexia (p=0.025), were the symptoms with the largest temporary impact of the chemotherapy. Unemployed women had worse physical functioning (p=0.046) and role functioning (p=0.005). Older women had more diarrhoea (p=0.013). The most qualified women had a worse score in financial difficulties scale (p=0.034). Women with advanced stage (III) underwent more deterioration in the body image (p=0.001) and were more concerned about the future (p=0.006). Women treated with anthracycline and taxane also had a worse perspective of the future (p=0.02). CONCLUSIONS: Adjuvant chemotherapy deteriorates the quality of life of patients with breast cancer, basically in physical functioning and body image areas. Asthenia and gastrointestinal toxicity are the side effects that affect patients most. Women need support if they are older, unemployed, more educated, and have stage III breast cancer treated with anthracycline and taxane based chemotherapy.

[Experience with a simplified format of decision making tool adjuvant! Online in breast cancer patients]. / Experiencia con un formato simplificado de la herramienta de ayuda en la toma de decisiones Adjuvant! Online en pacientes con cáncer de mama.

BACKGROUND: Adjuvant! Online estimates 10-year recurrence and mortality outcomes for breast cancer patients and predicts the effect of each type of treatment. Our purpose was to test the applicability by only analysing mortality estimations. METHOD: We present estimations of 66 women with definitive surgery and axillary staging for unilateral, unicentric, invasive adenocarcinoma, without metastatic or residual disease. Age, co-morbidity, estrogen receptor status, histological grade, tumor size, number of positive nodes, and hormone therapy or chemotherapy option, were the variables required. RESULTS: Median of survival estimations was 77%, cancer mortality 18% and mortality for other reasons 5%. The average of absolute risk reduction (ARR) with hormone therapy was 4%, with chemotherapy 4.5% and with combined treatment 7%. All the patients with some benefit decided to receive hormone therapy. Forty-three patients (65%) decided to receive chemotherapy and 23 (35%) did not. The average risk reduction with chemotherapy was 2% in those who decided not to receive chemotherapy and 8% in those who decided to receive it. There was an association between a chemotherapy decision and the estimation of the risk of breast cancer mortality (P=0.0001), risk of mortality for other reasons (P=0.038), and the ARR (P=0.0001). There were 6% of the patients with an ARR of 1%, 50% between 2-5% and 61.8% between 6-10%, who chose chemotherapy. CONCLUSIONS: All women opted for hormone therapy regardless of benefit. The reasons for choosing chemotherapy were the prognosis itself and the magnitude of benefit. Some patients decided to choose chemotherapy even when the benefit was minimal.