This study examined the impact of the Recurrence Score (RS) in Spanish breast cancer patients and explored the associations between clinicopathological markers and likelihood of change in treatment ...recommendations.
Enrollment was offered consecutively to eligible women with estrogen receptor-positive; human epidermal growth factor receptor 2-negative, node-negative breast cancer. Oncologists recorded treatment recommendation and confidence in it before and after knowing the patient’s RS.
Treatment recommendation changed in 32% of 107 patients enrolled: in 21% from chemohormonal (CHT) to hormonal therapy (HT) and in 11% from HT to CHT. RS was associated with the likelihood of change from HT to CHT (P < 0.001) and from CHT to HT (P < 0.001). Confidence of oncologists in treatment recommendations increased for 60% of cases. Higher tumor grade (P = 0.007) and a high proliferative index (Ki-67) (P = 0.023) were significantly associated with a greater chance of changing from HT to CHT, while positive progesterone receptor status (P = 0.002) with a greater probability of changing from CHT to HT.
Results from the first prospective European study are consistent with published experience and use of the RS as proposed in European clinical practice guidelines and provide evidence on how Oncotype DX and clinicopathological factors are complementary and patient selection may be improved.
To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination ...chemotherapy.
Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination.
The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351).
We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.
Src belongs to a family of cytoplasmic tyrosine kinases that play a key role in tumor initiation and progression. Src activation has been associated with a more aggressive neoplastic phenotype and ...induces resistance to platinum agents in preclinical models. The aim of our study was to assess the prognostic and/or predictive value of Src activation in stage II-III colon cancer patients. pSrc expression was assessed in paraffin-embedded tumor samples by immunohistochemistry (phospho Y418, ab4816, Abcam). Cases were classified by staining intensity in four categories: no staining (0), weak (1+), moderate (2+) and intense (3+) staining. A total of 487 patients were evaluated (240 stage II, 247 stage III), of whom 298 (61%) had received adjuvant chemotherapy. Staining was absent in 78 (16%), weak in 262 (54%), moderate in 103 (21%) and intense in 44 (9%). High pSrc expression was significantly associated with decreased 5-year disease-free survival (39% vs 63% for patients with high vs low pSrc expression, HR = 0.56 , P = .005) and overall survival (58% vs 74%, HR = 0.55, P = .02). Multivariate analysis confirmed pSrc expression as a significant prognostic factor both for DFS and OS, independent of age, gender, tumor stage, bowel obstruction/perforation or adjuvant chemotherapy. These findings illustrate the relevance of Src activation in colon cancer biology, conferring a poor prognosis to early stage colon cancer patients regardless of adjuvant chemotherapy. Our findings may help improve prognostic stratification of patients for clinical decissions, and open new avenues for potential pharmacological manipulation that may eventually improve patients' outcomes.
Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral ...therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.
Arsenic, a metalloid and naturally occurring element, is one of the most abundant elements in the earth's crust. Water is contaminated by arsenic through natural sources (underground water, minerals ...and geothermal processes) and anthropogenic sources such as mining, industrial processes, and the production and use of pesticides. Humans are exposed to arsenic mainly by drinking contaminated water, and secondarily through inhalation and skin contact. Arsenic exposure is associated with the development of vascular disease, including stroke, ischemic heart disease and peripheral vascular disease. Also, arsenic increases the risk of tumors of bladder, lungs, kidneys and liver, according to the International Agency for Research on Cancer and the Food and Drug Administration. Once ingested, an estimated 70–90% of inorganic arsenic is absorbed by the gastrointestinal tract and widely distributed through the blood to different organs, primarily to the liver, kidneys, lungs and bladder and secondarily to muscle and nerve tissue. Arsenic accumulates in the organs, especially in the liver. Its excretion mostly takes place through urination. The toxicokinetics of arsenic depends on the duration of exposure, pathway of ingestion, physicochemical characteristics of the compound, and affected biological species. The present review outlines of arsenic toxic effects focusing on different cancer types whit highest prevalence's by exposure to this metalloid and signaling pathways of carcinogenesis.
•Arsenic is a worldwide health problem mainly through drinking water.•Arsenic toxicity it depends on its reduction state.•Toxic effects of arsenic include different types of cancer.•Different arsenic carcinogenesis mechanism has been proposed.
We evaluated the success of a best practice alert (BPA) in recruiting underrepresented families into an autism spectrum disorder research cohort by comparing BPA-response outcomes (
Interested
,
...Declined
,
Enrolled
,
Dismissed
) in pediatric primary care practices (TCPs) serving diverse communities with those of subspecialty clinics. Compared to subspecialty clinics, TCPs had higher proportions of
Interested
responses for patients with private insurance (60.9% vs. 46.2%),
Dismissed
responses for patients with public insurance (30.1% vs. 20.0%), and
Interested
responses for non-white patients (47.7% vs. 33.3%). A targeted BPA can help researchers access more diverse groups and improve equitable representation. However, select groups more often had their alert dismissed, suggesting possible selection bias among some pediatricians regarding who should receive information about study opportunities.
Provider referral is one of the most influential factors in research recruitment. To ease referral burden on providers, we adapted the Best Practice Alert (BPA) in the
EPIC
Electronic Health Record ...and assessed its utility in recruiting pediatric patients with autism spectrum disorder for the national SPARK study. During a year-long surveillance, 1203 (64.0%) patients were
Interested
in SPARK and 223 enrolled. Another 754 participants not recruited via the BPA also enrolled; 35.5% of these participants completed their participation compared to 58.3% of BPA-referred participants. Results suggest that (a) a BPA can successfully engage providers in the study-referral process and (b) families who learn about research through their providers may be more engaged and effectively retained.
Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness ...of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant.
Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex.
This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up 95% confidence interval (CI) 54.5-70.8, there were no statistically significant differences between the sexes in progression-free survival 6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8 or in overall survival 10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5.
This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.
•Sex and gender are determinants of health inequalities and may affect treatments, tolerability, and therapeutic outcomes.•According to sex, subtle biological and clinical differences exist in advanced gastroesophageal adenocarcinoma.•Women with advanced gastroesophageal adenocarcinoma experience greater toxicity with therapeutic results comparable with men.•Stratification and analysis by sex in studies of gastroesophageal adenocarcinoma should be considered.
Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published ...evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug‐induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug‐drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.
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