Enhancing global access to cancer medicines.

Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high-quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.

Classification of anticancer drugs: an update with FDA- and EMA-approved drugs.

Anticancer systemic therapy comprises a complex and growing group of drugs. Some of the new agents with novel mechanisms of action that have appeared are difficult to fit in the groups of classical chemotherapy, hormones, tyrosine-kinase inhibitors, and monoclonal antibodies. We propose a classification based on two levels of information: the site of action and the mechanism of action. Regarding the former, drugs can exert their action in the tumor cell, the tumor vasculature, the immune system, or the endocrine system. The mechanism of action refers to the molecular target.

Factors influencing risk-based care of the childhood cancer survivor in the 21st century.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society.

The financial burden and distress of patients with cancer: Understanding and stepping-up action on the financial toxicity of cancer treatment.

"Financial toxicity" has now become a familiar term used in the discussion of cancer drugs, and it is gaining traction in the literature given the high price of newer classes of therapies. However, as a phenomenon in the contemporary treatment and care of people with cancer, financial toxicity is not fully understood, with the discussion on mitigation mainly geared toward interventions at the health system level. Although important, health policy prescriptions take time before their intended results manifest, if they are implemented at all. They require corresponding strategies at the individual patient level. In this review, the authors discuss the nature of financial toxicity, defined as the objective financial burden and subjective financial distress of patients with cancer, as a result of treatments using innovative drugs and concomitant health services. They discuss coping with financial toxicity by patients and how maladaptive coping leads to poor health and nonhealth outcomes. They cover management strategies for oncologists, including having the difficult and urgent conversation about the cost and value of cancer treatment, availability of and access to resources, and assessment of financial toxicity as part of supportive care in the provision of comprehensive cancer care. CA Cancer J Clin 2018;68:153-165. © 2018 American Cancer Society.

Antineoplastics for treating Alzheimer's disease and dementia: Evidence from preclinical and observational studies.

As the world population ages, there will be an increasing need for effective therapies for aging-associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion-like spreading of pathologies in treating AD.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Radiographic and serologic response in patients with unresectable hepatocellular carcinoma receiving systemic antineoplastic treatments: A trial-level analysis.

BACKGROUND: In a disease like unresectable hepatocellular carcinoma, overall survival is an inadequate outcome measure for evaluating the effectiveness of treatments given the high risk of death from liver failure. There is an unmet need for reliable alternative end points for clinical trials and daily clinical practice. To evaluate treatment response in patients with unresectable or metastatic hepatocellular carcinoma (mHCC), imaging-related end points are often used, whereas serologic end points have been developed for patients with serum alpha-fetoprotein levels >20 ng/mL. The objective of this study was to evaluate clinical trials that report concomitant assessment of radiographic and serologic response in patients with mHCC. METHODS: After a systematic review, studies that evaluated response according to radiographic and serologic criteria were selected. A correlation between progression-free survival (PFS) and overall survival (OS) was performed, and a linear regression of each response-related outcome measure with OS was reported. Finally, the effect of eight baseline variables on OS and response-related measures was evaluated. RESULTS: Twenty-six studies were included, including 16 first-line studies and 10 second-line studies. PFS and response rates demonstrated a significant relationship with OS, whereas disease control rates did not. The responses were correlated with OS, particularly in the first-line setting, after targeted therapy, and whenever assessment was early. Among the baseline variables, only performance status had a prognostic role, whereas hepatitis B virus-related liver disease was associated with higher radiographic response rates. CONCLUSIONS: PFS and radiographic and serologic response rates appear to be reliable intermediate end points in patients with mHCC who are undergoing systemic antineoplastic therapy. However, the serologic response is available earlier.

Efficacy and Safety of Trifluridine/Tipiracil-Containing Combinations in Colorectal Cancer and Other Advanced Solid Tumors: A Systematic Review.

We performed a systematic literature review to identify and summarize data from studies reporting clinical efficacy and safety outcomes for trifluridine/tipiracil (FTD/TPI) combined with other antineoplastic agents in advanced cancers, including metastatic colorectal cancer (mCRC). We conducted a systematic search on May 29, 2021, for studies reporting one or more efficacy or safety outcome with FTD/TPI-containing combinations. Our search yielded 1378 publications, with 38 records meeting selection criteria: 35 studies of FTD/TPI-containing combinations in mCRC (31 studies second line or later) and 3 studies in other tumor types. FTD/TPI plus bevacizumab was extensively studied, including 19 studies in chemorefractory mCRC. Median overall survival ranged 8.6-14.4 months and median progression-free survival 3.7-6.8 months with FTD/TPI plus bevacizumab in refractory mCRC. Based on one randomized and several retrospective studies, FTD/TPI plus bevacizumab was associated with improved outcomes compared with FTD/TPI monotherapy. FTD/TPI combinations with chemotherapy or other targeted agents were reported in small early-phase studies; preliminary data indicated higher antitumor activity for certain combinations. Overall, no safety concerns existed with FTD/TPI combinations; most common grade ≥ 3 adverse event was neutropenia, ranging 5%-100% across all studies. In studies comparing FTD/TPI combinations with monotherapy, grade ≥ 3 neutropenia appeared more frequently with combinations (29%-67%) vs. monotherapy (5%-41%). Discontinuation rates due to adverse events ranged 0%-11% for FTD/TPI plus bevacizumab and 0%-17% with other combinations. This systematic review supports feasibility and safety of FTD/TPI plus bevacizumab in refractory mCRC. Data on non-bevacizumab FTD/TPI combinations remain preliminary and need further validation.

Patient Priorities Concerning Treatment Decisions for Advanced Neuroendocrine Tumors Identified by Discrete Choice Experiments.

BACKGROUND: Patients with advanced neuroendocrine tumors (NETs) have multiple treatment options. Ideally, treatment decisions are shared between physician and patient; however, previous studies suggest that oncologists and patients place different value on treatment attributes such as adverse event (AE) rates. High-quality information on NET patient treatment preferences may facilitate patient-centered decision making by helping clinicians understand patient priorities. METHODS: This study used 2 discrete choice experiments (DCE) to elicit preferences of NET patients regarding advanced midgut and pancreatic NET (pNET) treatments. The DCEs used the "potentially all pairwise rankings of all possible alternatives" (PAPRIKA) method. The primary objective was to determine relative utility rankings for treatment attributes, including progression-free survival (PFS), treatment modality, and AE rates. Ranking of attribute profiles matching specific treatments was also determined. Levels for treatment attributes were obtained from randomized clinical trial data of NET treatments. RESULTS: One hundred and 10 participants completed the midgut NET DCE, and 132 completed the pNET DCE. Longer PFS was the highest ranked treatment attribute in 64.5% of participants in the midgut NET DCE, and in 59% in the pNET DCE. Approximately, 40% of participants in both scenarios prioritized lower AE rates or less invasive treatment modalities over PFS. Ranking of treatment profiles in the midgut NET scenario identified 60.9% of participants favoring peptide receptor radionuclide therapy (PRRT), and 30.0% somatostatin analogue dose escalation. CONCLUSION: NET patients have heterogeneous priorities when choosing between treatment options based on the results of 2 independent DCEs. These results highlight the importance of shared decision making for NET patients.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

Ovarian cancer classification and prognosis assessment model based on prognostic target genes in key microRNA-target gene networks.

BACKGROUND: The present study was designed to screen key microRNA (miRNA)-target gene networks for ovarian cancer (OC) and to classify and construct a risk assessment system for OC based on the target genes. METHODS: OC sample data of The Cancer Genome Atlas dataset and GSE26193, GSE30161, GSE63885 and GSE9891 datasets were retrospectively collected. Pearson correlation analysis and targeted analysis of miRNA and target gene were performed to screen key miRNA-target gene networks. Target genes associated with the prognosis of OC were screened from key miRNA-target gene networks for consensus clustering and least absolute shrinkage and selection operator-based regression machine learning analysis of OC samples. RESULTS: Twenty target genes of 2651 key miRNA-target gene pairs had significant prognostic correlation in each OC cohort, and OC was divided into three clusters. There were differences in prognostic outcome, biological pathways, immune cell abundance and susceptibility to immune checkpoint blockade (ICB) therapy and anti-tumor drugs among the three molecular clusters. S2 exhibited the least advantage in prognosis and immunotherapy response rate in the three molecular clusters, and the pathways regulating immunity, hypoxia, metabolism and promoting malignant progression of cancer, as well as infiltrating immune and stromal cell population abundance, were the highest in this cluster. An eight-target gene prognostic model was created, and the risk index obtained by using this model not only significantly distinguished the immune characteristics of the sample, but also predicted the response of the sample to ICB treatment, and helped to screen 36 potential anti-OC drugs. CONCLUSIONS: The present study provides a classification strategy for OC based on prognostic target genes in key miRNA-target gene networks, and creates a risk assessment system for predicting prognosis and response to ICB therapy in OC patients, providing molecular basis for prognosis and precise treatment of OC.

Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer.

PURPOSE: Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain. METHODS: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2- MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes. RESULTS: A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54-0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06-1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24-3.39, p < 0.01). CONCLUSION: This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations.

In vitro results with minimal blood toxicity of a combretastatin A4 analogue.

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL- 1, 0.1 mg mL- 1, 1.0 mg mL- 1, 10.0 mg mL- 1, 100.0 mg mL- 1, and 1,000.0 mg mL- 1. To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes.

Anticancer drugs are the first cause of drug-induced liver injury in a reference hospital.

Drug-induced liver injury (DILI) is a challenging liver disorder for hepatologists. We aimed to assess the pattern and causes of DILI in a tertiary hospital. We registered prospectively all patients referred with suspicion of DILI from 2018 to 2023. A total of 106 patients fulfilled the diagnostic criteria (30 caused by paracetamol were excluded; total number 76). The pattern of liver injury was hepatocellular in 55 (72%). Drugs causing DILI were antineoplastic (26%), antibiotics (24%), analgesics (12%), and recreational drugs (9%). Regarding clinical outcomes, 39 (51%) required hospitalization and 7 (9%) underwent a liver transplantation or died from acute liver injury. We identified 126 additional patients with DILI due to immune check-point inhibitors who were not referred to a liver disease specialist. Antineoplastic drugs have become the first cause of DILI in hospitals. A multidisciplinary approach and specific educational tools to increase DILI awareness are needed among different specialists.

A Real-World Disproportionality Analysis of Drug-Induced Immune Hemolytic Anemia in the FDA Adverse Event Reporting System.

BACKGROUND: Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening pharmacogenic hematological adverse effect. Updating the risk of DIIHA among the currently available drugs based on spontaneously reported adverse event data is of great significance. OBJECTIVE: This study aimed to identify the top 50 drugs associated with immune hemolytic anemia in adults as well as common drugs that could cause immune hemolytic anemia in children based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted adverse events (AE) in the FAERS database from Q1 2004 to Q3 2022 using Open vigil2.1. We use the high-level term "anaemias haemolytic immune" according to the Medical Dictionary for Regulatory Activities (MedDRA) Dictionary (version 24.0). The reported correlation between drugs and DIIHA risk was identified by reported odds ratio (ROR) and proportional reporting ratio (PRR). RESULTS: There were 10500309 AEs in FAERS from 2004Q1 to 2022Q3, of which 2326 (0.02%) were DIIHA cases. The incidence of DIIHA is comparable between males and females. The most common drugs associated with DIIHA in adults and children are summarized according to the number of AE reports. The top 3 categories in terms of quantity of drugs are antineoplastic agents, immunosuppressants, and antibiotics for systemic use. The top 5 drugs in terms of ROR and PRR are alemtuzumab, daclizumab, fludarabine, busulfan, and bendamustine in adults, with entecavir, treosulfan, vinorelbine, pegademase, and alemtuzumab for children. CONCLUSIONS: Our study identified the most common drugs that could induce DIIHA in adults and children, as well as the respective ROR and PRR value to discover new drug signals. This study provides references to clinicians for the management of rare DIIHA.

OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer. Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively. Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n =311 [87.6%]; Brazil: n = 1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line. Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

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Real-world treatment of metastatic hormone-sensitive prostate cancer in the USA, Europe and Asia.

Aim: To characterize real-world patients with metastatic hormone-sensitive prostate cancer (mHSPC) and treating physicians and evaluate treatment trends and baseline concordance versus guidelines internationally. Materials & methods: Retrospective, cross-sectional data from the Ipsos Global Oncology Monitor database 2018-2020 were used for descriptive analysis of mHSPC patients, treating physicians and treatment utilization. Results: Among the 6198 mHSPC patients from five countries, the most common treatment was either androgen deprivation therapy (ADT) monotherapy or first-generation androgen receptor inhibitor + ADT. Second-generation androgen receptor inhibitor use was only initiating but increasing over the study period. Conclusion: Despite contemporaneous guidelines recommending treatment intensification of ADT in combination with novel antihormonals or docetaxel, 76.1% of reported mHSPC patients received non-guideline-concordant care.

Prostate cancer is the second most common cancer among men worldwide and a leading cause of cancer-related death globally. Metastatic hormone-sensitive prostate cancer (mHSPC) refers to the stage of prostate cancer where it has spread to other parts of the body ('metastatic') but still responds to hormonal therapy ('hormone-sensitive'), such as androgen deprivation therapy (ADT). Treatment guidelines around the world for men with mHSPC have changed over time, but there remains a lack of understanding of how well guidelines are followed in real-world practice. Consequently, this study analyzes real-world data from five countries between 2018 and 2020 to understand treatment patterns, baseline concordance versus guidelines and potential drivers of treatment trends. The study found prevalent use of ADT monotherapy and older antihormonal agents, and only marginal but increasing use of novel antihormonals in real-world practice. These practices deviate from guidelines from the study period, which generally recommended ADT combination with either newer antihormonal agents or docetaxel for patients with mHSPC. Overall, the proportion of the 6198 patients treated with non­guideline-concordant therapies was 76.1%. Since guideline-recommended care is associated with better outcomes, this baselining finding highlights the need for appropriate treatment selection and intensification for mHSPC patients.

Rising cases of drug-induced pulmonary fibrosis: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database, 2000-2022.

PURPOSE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications. METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms "pulmonary fibrosis" and "idiopathic pulmonary fibrosis" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function. RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%). CONCLUSION: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

Antineoplastic therapy is an independent risk factor for dental caries in childhood cancer patients: a retrospective cohort study.

PURPOSE: To evaluate the antineoplastic therapy (AT) as a risk factor for dental caries lesions independent of other risk factors such as income, family education, stimulated salivary flow rate, hygiene habits, frequency of sugar intake, and microbiota in childhood cancer (CC) patients. METHODS: 72 individuals were divided into CC patients (n=36) and healthy individuals (control group - CT n=36). Demographic data, hygiene habits, frequency of sugar intake, CC type, and AT were collected. Stimulated salivary flow rate was measured and the presence and concentration of Streptococcus mutans were assessed using a real-time polymerase chain reaction (qPCR) technique. Clinical evaluations included plaque index (PI) and decayed-missing-filled-teeth index (dmft/DMFT). Descriptive statistics, T-test, Mann-Whitney test, chi-square test, Fisher's exact test, and two-way analysis of variance were used for data analysis (p<0.05). RESULTS: At the time of oral evaluation, both groups exhibited similar ages with means of 12.0±3.9 years old for CC and 12.0±4.0 years old for CT patients. All CC patients underwent chemotherapy with nine also undergoing radiotherapy. Significant differences were observed between the groups in terms of color/race, income, family education, and hygiene habits. However, no statistically significant differences were found between groups regarding the frequency of sugar intake, stimulated salivary flow rate, or the concentration of Streptococcus mutans (qPCR technique). For clinical parameters, the DMF (CC:1.80, CT: 0.75), decayed (CC: 0.88, CT: 0.19), missing (CC: 0.25, CT:0), and PI (CC: 30.5%, CT: 22.6%) were higher in the CC group (p<0.05). CONCLUSION: Childhood cancer (CC) patients undergoing antineoplastic therapy (AT) exhibit a higher prevalence of dental caries, regardless of income/education, frequency of sugar intake, stimulated salivary flow rate, and microbiota.

Management of cutaneous adverse events caused by antineoplastic therapies: a single-center experience.

INTRODUCTION: Cutaneous adverse events can occur in patients treated with antineoplastic treatments, albeit their incidence has not been defined yet. The clinical presentation of CAEs related to anticancer treatments can vary. The purpose of our study is to characterize skin toxicities during oncological treatments, manage such adverse events to improve patients' quality of life, and ensure therapeutic adherence. METHODS: We conducted a single-center prospective study which provided the enrollment of all patients referred to the Skin Toxicity Outpatient Clinic for the occurrence of cutaneous adverse events secondary to an ongoing antineoplastic treatment, between July 2021 and June 2023. We analyzed clinical features, and we described our therapeutic approach. RESULTS: Based on the type of drug assumed, chemotherapy-induced skin toxicity in 24 (38.7%) of the 62 evaluated patients, target therapies in 18 (29.0%), CDK4/6 cyclin inhibitors in 12 (19.4%), and immunotherapy in 6 (9.7%), while skin adverse events secondary to hormone therapy were seen in two patients. The most common cutaneous adverse event in our experience was rosaceiform rash of the face, followed by eczematous rash, hand-foot syndrome, and folliculitis. CONCLUSION: The present study is aimed at describing the variability and heterogeneity of clinical manifestations of different pharmacological classes used in oncological patients, as well as the different pathogenesis of skin damage. Chemotherapy very frequently causes skin toxicities that are often underestimated by clinicians. Their adequate recognition and optimal treatment lead to total recovery and allow better adhesion to chemotherapy.