Sex and gender may influence the epidemiology, pathogenesis, and prognosis of cancer. This narrative review describes sex and gender differences in the epidemiology and pathogenesis of cancer, and how such differences may impact the pharmacodynamics and pharmacokinetics of cancer treatment. For most types of cancer unrelated to reproductive function, incidence is higher in males than in females, except for gallbladder and thyroid cancers, which are much more common in women. Cancer mortality is higher in men than women; women account for a larger proportion of survivors. These differences may be related to biological differences in pathogenesis or differences in behaviors relating to cancer risk or detection. The pharmacokinetics and pharmacodynamics of cancer therapies also differ between sexes due to differences in body composition, physiology, and receptor expression. Overall, sex and gender are essential variables to be considered in research and clinical practice, influencing diagnosis, subtyping (biomarkers), prognostication, treatment, and dosage.

Lung cancer continues to be the leading cause of cancer mortality and a serious health problem despite the numerous advances made in the last decade and the rapid advance of research in this field.... Tweetable abstract The time has come to offer targeted therapy to patients with earlier-stage non-small-cell lung cancer, which could represent an important qualitative leap in the treatment of lun... Lay abstract Despite major therapeutic advances over the last decade, lung cancer continues to present the highest mortality rate of all cancers. Precision and personalized therapy directed at spec...

Differences between the biological sexes have long been observed in cancer incidence and prevalence, and in treatment outcomes including efficacy and toxicity. Ideally, there should be sufficient information to improve the individualization of cancer treatment by incorporating sex into treatment decisions. Necessary information should include: the nature and source of these differences; whether inherent to the specific cancer (such as molecular profiles, metabolic behaviors, and immune responses); the pathophysiological mechanisms of the specific cancer; or the pharmacokinetic and pharmacodynamic profiles of different cancer drugs. The influence of gender, which is defined as the sociocultural construct that determines societal norms for males and females, should also be included in personalized decision-making. This review aimed to describe the current evidence on the impact of sex and gender on treatment effects, outcomes, and toxicity profiles in cancer patients. Data for the influence of gender were negligible, whereas clinical studies and meta-analyses in different cancer types have identified differences between males and females in the effectiveness on survival outcomes of immunotherapy, chemotherapy, targeted therapy, and radiotherapy. Similarly, toxicity profiles of different cancer treatments varied between sexes. Based on these observed differences, it seems clear that sex should be included as an important variable when individualizing treatment; however, more research into sex- and gender-related differences in cancer treatment efficacy and toxicity, and the causes for these differences, is required before this can be fully incorporated into individualized treatment programs in real-world clinical practice.

Purpose: Identifying patient characteristics that define a worse disease prognosis or “high tumor burden” (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice. Patients and Methods: A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience. Results: HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively. Conclusion: In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.