Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric cancer: A pooled analysis of four randomised trials

Davidson, Michael; Wagner, Anna Dorothea; Kouvelakis, Kyriakos; Nanji, Henry; Starling, Naureen; Chau, Ian; Watkins, David; S, Rao; Peckitt, Clare; Cunningham, David

doi:10.1016/j.ejca.2019.08.010

Cited by 49 publications

(43 citation statements)

References 27 publications

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“…In addition to the observed survival differences, toxicity rates and number of completed chemotherapy cycles also varied between males and females in our study. The occurrence of higher rates of toxicity in females has previously been reported for a number of different cytotoxic drugs and relates to both haematological and non-haematological toxicities [22,26,27]. Although the increased susceptibility of toxicities such as nausea and alopecia may be influenced by differing perceptions between females and males, differences in the occurrence of objective haematological parameters supports the notion of sex-specific variation in drug exposure and sensitivity.…”

Section: Discussionmentioning

confidence: 53%

Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)

Athauda

Nankivell

Langley

et al. 2020

European Journal of Cancer

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Background: There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer. Patients and methods: Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and 70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received. Results: 3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) 70 years). A significant improvement in overall survival

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Section: Discussionmentioning

confidence: 53%

Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)

Athauda

Nankivell

Langley

et al. 2020

European Journal of Cancer

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“…In addition, a longitudinal study of 237 breast cancer patients demonstrated that impacts of lost income, health expenses, and lost unpaid work lasted at least 18 months [24]. Further, it has been shown women with cancer experience have more anxiety and depression than men [25,26] as well as more severe side effects from cancer treatments [27], supporting their interest in research to abrogate these issues. These findings may be attributed to differences in cancer diagnosis between men and women and further research is needed to better understand preferences by gender, cancer type, and how that may lead to targeted communication for women versus men in biobank settings.…”

Section: Plos Onementioning

confidence: 99%

Utilizing a large-scale biobanking registry to assess patient priorities and preferences for cancer research and education

et al. 2021

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Patients consented to biobanking studies typically do not specify research conducted on their samples and data. Our objective was to gauge cancer biobanking participant preferences on research topics. Patient-participants of a biobanking study at a comprehensive cancer center who had an appointment within the last 5 years, had a valid email address, and with a last known vital status of alive, were emailed a newsletter containing a link to a survey about preferences and priorities for research. The survey assessed demographics and research interest in three domains: cancer site, cancer-related topics, and issues faced by cancer patients. 37,384 participants were contacted through email to participate in the survey. 16,158 participants (43.2%) opened the email, 1,626 (4.3% overall, 10% of those who opened the email) completed the survey, and 1,291 (79.4% of those who completed the survey) selected at least one research priority. Among those who selected at least one research priorities for cancer-relevant topics, the most commonly selected were cancer treatment (66%), clinical trials (54%), and cancer prevention (53%). Similarly, the most selected priorities for cancer-related issues faced by patients were physical side effects of cancer (57%), talking to the oncologist (53%), and emotional challenges due to cancer (47%). Differences by gender were observed, with females reporting more interest in research generally. Cancer patients participating in a biobanking protocol prioritized research on treatments, prevention and side effects, which varied by gender.

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“…As previously mentioned, SNP variants have been previously correlated with chemotherapy toxicity [33][34][35]. Other factors such as chemotherapy scheme, dosage, sex, and age have also been implicated in the development and severity of toxicity [7,[36][37][38]. However, only a few studies have developed comprehensive models that incorporate genetic and non-genetic factors to predict toxicity [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer

et al. 2021

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Background Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.7%). No guidelines have been development for platinum. Herein, we present association between clinical factors and common SNPs in the development of grade 3–4 toxicity. Methods Retrospectively, 224 clinical records of GC patient were screened, of which 93 patients were incorporated into the study. Eleven SNPs with minor allelic frequency above 5% in GSTP1, ERCC2, ERCC1, TP53, UMPS, SHMT1, MTHFR, ABCC2 and DPYD were assessed. Association between patient clinical characteristics and toxicity was estimated using logistic regression models and classification algorithms. Results Reported grade ≤ 2 and 3–4 toxicities were 64.6% (61/93) and 34.4% (32/93) respectively. Selected DPYD SNPs were associated with higher toxicity (rs1801265; OR = 4.20; 95% CI = 1.70–10.95, p = 0.002), while others displayed a trend towards lower toxicity (rs1801159; OR = 0.45; 95% CI = 0.19–1.08; p = 0.071). Combination of paired SNPs demonstrated significant associations in DPYD (rs1801265), UMPS (rs1801019), ABCC2 (rs717620) and SHMT1 (rs1979277). Using multivariate logistic regression that combined age, sex, peri-operative chemotherapy, 5-FU regimen, the binary combination of the SNPs DPYD (rs1801265) + ABCC2 (rs717620), and DPYD (rs1801159) displayed the best predictive performance. A nomogram was constructed to assess the risk of developing overall toxicity. Conclusion Pending further validation, this model could predict chemotherapy associated toxicity and improve GC patient quality of life.

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Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric cancer: A pooled analysis of four randomised trials

Cited by 49 publications

References 27 publications

Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)

Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03)

Utilizing a large-scale biobanking registry to assess patient priorities and preferences for cancer research and education

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer

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