ABSTRACT
PURPOSE: Patient selection in phase 1 clinical trials (Ph1t) continues to be a challenge. The aim of this study was to develop a user-friendly prognostic calculator for predicting overall survival (OS) outcomes in patients to be included in Ph1t with immune checkpoint inhibitors (ICIs) or targeted agents (TAs) based on clinical parameters assessed at baseline. METHODS: Using a training cohort with consecutive patients from the VHIO phase 1 unit, we constructed a prognostic model to predict median OS (mOS) as a primary endpoint and 3-month (3m) OS rate as a secondary endpoint. The model was validated in an internal cohort after temporal data splitting and represented as a web application. RESULTS: We recruited 799 patients (training and validation sets, 558 and 241, respectively). Median follow-up was 21.2 months (m), mOS was 10.2 m (95% CI, 9.3-12.7) for ICIs cohort and 7.7 m (95% CI, 6.6-8.6) for TAs cohort. In the multivariable analysis, six prognostic variables were independently associated with OS - ECOG, number of metastatic sites, presence of liver metastases, derived neutrophils/(leukocytes minus neutrophils) ratio [dNLR], albumin and lactate dehydrogenase (LDH) levels. The phase 1 prognostic online (PIPO) calculator showed adequate discrimination and calibration performance for OS, with C-statistics of 0.71 (95% CI 0.64-0.78) in the validation set. The overall accuracy of the model for 3m OS prediction was 87.2% (95% CI 85%-90%). CONCLUSIONS: PIPO is a user-friendly objective and interactive tool to calculate specific survival probabilities for each patient before enrolment in a Ph1t. The tool is available at https://pipo.vhio.net/.
Subject(s)
Internet-Based Intervention/trends , Patient Portals/standards , Patient Selection , Aged , Clinical Trials as Topic , Female , Humans , Male , Medical Oncology , Middle Aged , PrognosisABSTRACT
BACKGROUND & AIMS: Beyond the quantity of carbohydrate intake, further research is needed on the relevance of carbohydrate quality. Thus, we evaluated the association between an a priori defined carbohydrate quality index (CQI) and the incidence of breast cancer (BC) in a Mediterranean cohort study. METHODS: We used a validated semi-quantitative 136-item food-frequency questionnaire (FFQ) in a prospective follow-up study of 10,812 middle-aged women. We evaluated at baseline the CQI following 4 criteria: dietary fiber intake, glycemic index, whole-grain:total-grain carbohydrates ratio and the solid carbohydrate:total carbohydrate ratio. Subjects were classified into quartiles according to the final CQI score. RESULTS: During a median follow-up of 11.8 years, we confirmed 101 incident cases of BC. Our study suggests that a higher quality of carbohydrate intake, as measured by the baseline CQI, was associated with a lower risk of BC [HR Q4 vs. Q1 0.39 (95% CI 0.17, 0.87)]. Particularly, a higher whole-grain:total-grain carbohydrates ratio was associated with lower risk of BC [HR T3 vs. T1 0.56 (0.34, 0.90)]. When we stratified by menopausal status, we found an inverse association between CQI and BC in the comparison of extreme quartiles among premenopausal women. CONCLUSIONS: In this Mediterranean cohort, a better quality of dietary carbohydrate intake showed a significant inverse association with the incidence of BC, which suggests that strategies for cancer prevention should highlight the quality of this macronutrient.
Subject(s)
Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Diet, Healthy/statistics & numerical data , Diet/adverse effects , Dietary Carbohydrates/analysis , Adult , Diet Surveys , Female , Glycemic Index , Humans , Incidence , Middle Aged , Prospective Studies , Risk Factors , Spain/epidemiology , Whole GrainsABSTRACT
OBJECTIVE: The aim of this study was to assess body shape trajectories in childhood and midlife in relation to subsequent risk of breast cancer (BC) in a Mediterranean cohort. DESIGN: The 'Seguimiento Universidad de Navarra' (SUN) Project is a dynamic prospective cohort study of university graduates initiated in 1999. With a group-based modelling approach, we assessed body shape trajectories from age 5 to 40 years. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for BC after the age of 40 years according to the body shape trajectory. SETTING: City of Pamplona, in the North of Spain. PARTICIPANTS: 6498 women with a mean age of 40 years (sd 9). RESULTS: We identified four distinct body shape trajectories ('childhood lean-midlife increase' (19·9 %), 'childhood medium-midlife stable' (53 %), 'childhood heavy-midlife stable' (21 %) and 'childhood heavy-midlife increase' (6·1 %)). Among 54 978 women-years of follow-up, we confirmed eighty-two incident cases of BC. Women in the 'childhood lean-midlife increase' group showed a higher risk of BC (HR = 1·84, 95 % CI 1·11, 3·04) compared with women in the 'childhood medium-midlife stable' category. This association was stronger for postmenopausal BC (HR = 2·42, 95 % CI 1·07, 5·48). CONCLUSIONS: Our results suggest a role for lifetime adiposity in breast carcinogenesis.
Subject(s)
Breast Neoplasms , Somatotypes , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Prospective Studies , Risk Factors , Spain , Young AdultABSTRACT
Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03-2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11-3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.
Subject(s)
Binge Drinking , Breast Neoplasms , Adult , Binge Drinking/complications , Binge Drinking/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Risk Factors , Spain/epidemiologyABSTRACT
BACKGROUND: Biological and epidemiological evidence supports an inverse association of phenolic acids with obesity-related chronic diseases. However, no previous study has prospectively evaluated the relationship between subclasses and individual compounds of phenolic acids and the risk of postmenopausal breast cancer, one of the most important and prevalent obesity-related cancer sites. OBJECTIVE: This study examined associations between subclasses of phenolic acids, including hydroxycinnamic and hydroxybenzoic acids intake, and risk of breast cancer. DESIGN: The Seguimiento Universidad de Navarra (SUN) Project is a dynamic, permanently open prospective cohort which started in 1999. PARTICIPANTS/SETTING: Participants were 10,812 middle-aged women. All of them were university graduates. MAIN OUTCOME MEASURES: Usual diet was assessed at baseline and after 10 years of follow-up with a 136-item food frequency questionnaire. Phenolic acid intake was calculated by matching food consumption with the Phenol-Explorer database on phenolic acids content of each reported food item. STATISTICAL ANALYSIS PERFORMED: Participants were classified according to tertiles of subclasses or individual compounds of phenolic acids. Cox regression models were fitted to estimate multivariable-adjusted hazard ratios and 95% CIs for breast cancer incidence. RESULTS: Over an average of 11.8 years of follow-up, 101 incident cases of breast cancer were confirmed. After multivariable adjustment, an inverse association between hydroxycinnamic acids intake and breast cancer was observed (hazard ratio third tertile vs first tertile 0.37, 95% CI 0.16 to 0.85; P for trend=0.029) among postmenopausal women. Specifically, chlorogenic acids (3-, 4-, and 5- caffeoylquinic acids) showed the strongest inverse association (hazard ratio third tertile vs first tertile 0.33, 95% CI 0.14 to 0.78; P for trend=0.012). CONCLUSIONS: A higher intake of hydroxycinnamic acids, especially from chlorogenic acids-present in coffee, fruits, and vegetables-was associated with a lower incidence of breast cancer among postmenopausal women. Future observational studies are needed to corroborate these results.
Subject(s)
Breast Neoplasms/epidemiology , Coumaric Acids/administration & dosage , Diet, Mediterranean , Hydroxybenzoates/administration & dosage , Adult , Chlorogenic Acid/administration & dosage , Coffee , Cohort Studies , Female , Fruit , Humans , Middle Aged , Postmenopause , Prospective Studies , Quinic Acid/administration & dosage , Quinic Acid/analogs & derivatives , Risk Factors , Spain , VegetablesABSTRACT
Polyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression. In vivo and in vitro studies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project - a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10·3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3 v. T1 0·31 (95 % CI 0·13, 0·77; Ptrend=0·010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.
Subject(s)
Breast Neoplasms/epidemiology , Polyphenols/administration & dosage , Adult , Cohort Studies , Female , Humans , Middle Aged , Prospective Studies , Risk FactorsABSTRACT
No disponible
Subject(s)
Humans , Male , Adult , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography/methods , Head and Neck Neoplasms , Thyroid Neoplasms , Granuloma, Plasma Cell , Diagnosis, Differential , Incidental FindingsABSTRACT
OBJETIVO: Sugerir recomendaciones para ayudar al paciente con cáncer avanzado, o al familiar, que plantea el uso de marihuana u otras formas de cannabis medicinal como tratamiento sintomático o de soporte. MÉTODO: A partir de un ejemplo real, se presenta un resumen de la farmacología de los cannabinoides naturales y sintéticos, de la evidencia sobre su eficacia como tratamiento sintomático en cáncer avanzado, y de la actitud y expectativas del paciente o la familia que plantea el uso medicinal del cannabis. Resultado: El cannabis medicinal contiene más de 60 cannabinoides naturales (de los cuales el delta-9-tetrahidrocannabinol es el más importante) y otras sustancias. En nuestro medio, los pacientes que plantean el empleo de cannabis como tratamiento sintomático no solicitan cannabinoides sintéticos aprobados en otros países sino la hierba de cannabis o sus derivados. Lo suelen consumir fumado (lo que favorece la aparición más temprana de niveles plasmáticos) o en infusión. El consumo de cannabis medicinal se presta a una gran variabilidad en las concentraciones plasmáticas de delta-9-tetrahidrocannabinol. Existen pocos estudios que evalúen científicamente la eficacia del cannabis medicinal en el control de síntomas del paciente con cáncer avanzado. Los estudios realizados con cannabinoides sintéticos son metodológicamente muy limitados, pero aportan cierta evidencia sobre el efecto de los cannabinoides en el alivio del dolor (también como coadyuvante), de las náuseas y de los vómitos inducidos por quimioterapia en el enfermo oncológico. No hay evidencia suficiente para afirmar su eficacia en el tratamiento de la hiporexia. Los efectos secundarios de los cannabinoides en dosis moderadas (como en el uso de cannabis medicinal) son en su mayoría leves y de perfil neuropsicológico. La actitud y las expectativas del paciente, junto con el modo de empleo del cannabis medicinal, pueden favorecer que parte de su beneficio se deba a un efecto placebo. CONCLUSIONES: El cannabis medicinal no parece ser tan activo como esperan los pacientes ni tan tóxico como suponen muchos profesionales. Para responder al paciente con cáncer avanzado que plantea su uso como tratamiento sintomático es aconsejable evitar prejuicios, actuar con respeto y prudencia y buscar el beneficio sintomático del paciente
OBJECTIVE: To contribute ideas to answer advanced cancer patients asking about the use of medicinal cannabis as a symptomatic treatment. Method: Based on a real example, we present a summary of the pharmacology of natural and synthetic cannabinoids, the evidence on its effectiveness as a symptomatic treatment in advanced cancer, and the patient's attitude and expectations raised by the medicinal use of cannabis. RESULT: There are more than 60 different cannabinoids (the most relevant: delta-9-tetrahydrocannabinol) and other substances in cannabis. In our setting, patients who ask about the use of cannabis as a symptomatic treatment do not look for synthetic cannabinoids approved in other countries, but rather prefer herbal cannabis or its derivatives. They usually consume smoked cannabis (favoring the earlier onset of plasma levels) or, rarely, in infusion. Use of medicinal cannabis causes a wide variation in plasma concentrations of delta-9-tetrahydrocannabinol. There is evidence supporting a certain effect of synthetic cannabinoids in pain relief (also as an adjuvant), and as antiemetic for chemotherapy-induced nausea and vomiting in cancer PATIENTS: This evidence is based primarily on results of studies with limited methodological quality. There is insufficient evidence to assert its effectiveness in the treatment of anorexia. Side effects of moderate doses of synthetic cannabinoids or medicinal cannabis are mostly mild, as well as their psycho-neurological profile. The attitude and expectations of the patient, and the way to consume of medical cannabis may favor that part of its benefit may be due to a placebo effect. CONCLUSIONS: Medicinal cannabis does not seem as active as patients expect, or as toxic as many professionals suspect. To respond to the advanced cancer patient asking about their use as symptomatic treatment is advisable to avoid prejudice, to respect and to act with caution seeking the patient's symptomatic Benefit
