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.

Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies.

The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer (BC) has prompted the exploration of novel therapeutic strategies targeting shared metabolic pathways. This review focuses on the emerging evidence surrounding the potential anti-cancer effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in the context of BC. Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of BC cells, induce apoptosis, and modulate key cellular signaling pathways. These mechanisms include the activation of AMP-activated protein kinase (AMPK), suppression of mammalian target of rapamycin (mTOR) signaling, and regulation of lipid metabolism and inflammatory mediators. The combination of SGLT2 inhibitors with conventional treatments, including chemotherapy and radiotherapy, as well as targeted therapies like phosphoinositide 3-kinases (PI3K) inhibitors, has shown promising results in enhancing the anti-cancer efficacy and potentially reducing treatment-related toxicities. The identification of specific biomarkers or genetic signatures that predict responsiveness to SGLT2 inhibitor therapy could enable more personalized treatment selection and optimization, particularly for challenging BC subtypes [e, g., triple negative BC (TNBC)]. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive BC care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of BC, including the aggressive and chemo-resistant TNBC.

Chemotherapy's effects on autophagy in the treatment of Hodgkin's lymphoma: a scoping review.

BACKGROUND: Classical Hodgkin Lymphomas (HL) are a unique malignant growth with an excellent initial prognosis. However, 10-30% of patients will still relapse after remission. One primary cellular function that has been the focus of tumor progression is autophagy. This process can preserve cellular homeostasis under stressful conditions. Several studies have shown that autophagy may play a role in developing HL. Therefore, this review aimed to explore chemotherapy's effect on autophagy in HL, and the effects of autophagy on HL. METHODS: A scoping review in line with the published PRISMA extension for scoping reviews (PRISMA-ScR) was conducted. A literature search was conducted on the MEDLINE database and the Cochrane Central Register of Controlled Trials (CENTRAL). All results were retrieved and screened, and the resulting articles were synthesized narratively. RESULTS: The results showed that some cancer chemotherapy also induces autophagic flux. Although the data on HL is limited, since the mechanisms of action of these drugs are similar, we can infer a similar relationship. However, this increased autophagy activity may reflect a mechanism for increasing tumor growth or a cellular compensation to inhibit its growth. Although evidence supports both views, we argued that autophagy allowed cancer cells to resist cell death, mainly due to DNA damage caused by cytotoxic drugs. CONCLUSION: Autophagy reflects the cell's adaptation to survive and explains why chemotherapy generally induces autophagy functions. However, further research on autophagy inhibition is needed as it presents a viable treatment strategy, especially against drug-resistant populations that may arise from HL chemotherapy regimens.

Niraparib as maintenance therapy in Japan: a retrospective observational study using a Japanese claims database.

OBJECTIVE: Epithelial ovarian cancer (EOC) is the leading cause of female mortality in gynecologic malignancies, with a rising incidence in Japan. This study aimed to validate the treatment patterns and safety of niraparib as maintenance therapy for EOC following initial chemotherapy in clinical practice in Japan. METHODS: Leveraging claims data between April 2008 and December 2022, this descriptive study comprised EOC-diagnosed patients receiving initial platinum-based chemotherapy, debulking surgery, and niraparib as maintenance therapy. Patient characteristics, prescription status, transfusion details, and laboratory data were assessed and reported as summary statistics and frequencies. RESULTS: Among 291 patients, the median age was 64.0 years and 94.5% received a 200-mg daily dose of niraparib. At week 12, 78.7% (229/291) continued niraparib treatment, 21.3% (62/291) discontinued, and 52.2% (152/291) required treatment interruptions. Of the 62 patients who discontinued treatment, 27 patients initiated subsequent EOC treatment within 12 weeks following niraparib discontinuation. Blood transfusions were needed in 10.3% (30/291), and of 55 patients with available laboratory data, 61.8% (34/55) had decreased platelet count <100,000/µL, 25.5% (14/55) had decreased hemoglobin level <8 g/dL, and 22.7% (5/22) had decreased neutrophil count <1,000/µL, meeting the criteria for treatment interruption. Among those with thrombocytopenia, 88.2% (30/34) were able to either resume or continue treatment. CONCLUSION: Niraparib demonstrated favorable tolerability in Japanese patients with advanced EOC, with effective management of thrombocytopenia through dose adjustments and supportive care, supporting its viability as post-chemotherapy maintenance therapy.

Patient reported medication-related problems, adherence and waste of oral anticancer medication over time.

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time. METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data. RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews. CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.

Drug resistance in human cancers - Mechanisms and implications.

Cancers have complex etiology and pose a significant impact from the health care perspective apart from the socio-economic implications. The enormity of challenge posed by cancers can be understood from the fact that clinical trials for cancer therapy has yielded minimum potential promises compared to those obtained for other diseases. Surgery, chemotherapy and radiotherapy continue to be the mainstay therapeutic options for cancers. Among the challenges posed by these options, induced resistance to chemotherapeutic drugs is probably the most significant contributor for poor prognosis and ineffectiveness of the therapy. Drug resistance is a property exhibited by almost all cancer types including carcinomas, leukemias, myelomas, sarcomas and lymphomas. The mechanisms by which drug resistance is induced include the factors within the tumor microenvironment, mutations in the genes responsible for drug metabolism, changes in the surface drug receptors and increased drug efflux. We present here comprehensively the drug resistance in cancers along with their mechanisms. Also, apart from resistance to regularly used chemotherapeutic drugs, we present resistance induction to new generation therapeutic agents such as monoclonal antibodies. Finally, we have discussed the experimental approaches to understand the mechanisms underlying induction of drug resistance and potential ways to mitigate induced drug resistance.

A case for the use of chemotherapy in hereditary mitochondrial optic neuropathies: Successful administration of cisplatin/etoposide in a male patient with testicular seminoma and Leber's hereditary optic neuropathy.

We report on the successful use of chemotherapy for treatment of stage 2B testicular seminoma in a carrier of the Leber's hereditary optic neuropathy 11778 mitochondrial mutation. Neurotoxic chemotherapy may not prompt disease conversion.

Analysis of risk factors for disease progression after salvage radiation therapy with androgen deprivation therapy in prostate cancer patients who have prostate-specific antigen persistence after radical prostatectomy.

PURPOSE: To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). MATERIALS AND METHODS: We analyzed 57 patients who received SRT with ADT between 2013 and 2019 due to PSA persistence after RP. The endpoint was disease progression defined by biochemical recurrence or clinical recurrence. Age, Pre-RP PSA level, Gleason score, pathologic stage, presence of pelvic lymph node dissection, surgical margins, and PSA at 6-8 weeks after RP were analyzed as predictive factors for disease progression. Kaplan-Meier method and Cox regression models were used for data analysis. RESULTS: At a median follow-up of 38 months (interquartile range, 26-61), 17 patients had disease progression. Pathologic T stage (pT3b vs. pT3a or lower; hazard ratio [HR] = 9.20; p = 0.035) and PSA level at 6-8 weeks after RP (≥2.04 vs. <2.04 ng/mL; HR = 5.85; p = 0.002) were predictors of disease progression. The 5-year disease progression-free survival rate was 46.7% in pT3b group as compared to 92.9 % in pT3a or lower group, and 18.4% for PSA ≥2.04 ng/mL after RP as compared to 79.2% for PSA <2.04 ng/mL. CONCLUSION: Pathological T stage (pT3b) and post RP PSA ≥2.04 ng/mL are independent risk factors of disease progression after SRT with ADT in patients with PSA persistence after RP.

Fertility Assessment after Ovarian Transposition in Children and Young Women Treated for a Malignant Tumor.

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT's effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages.

Polypharmacy and drug interactions in older patients with cancer receiving chemotherapy: associated factors.

BACKGROUND: Polypharmacy in older adults with cancer receiving chemotherapy leads to increased risks of drug interactions, translating in potential hazardous health outcomes. This study aims to assess the prevalence of polypharmacy, drug-drug interactions (DDIs), and severe-drug interactions (SDIs) in older patients with cancer. Antineoplastic agents (ANAs) involvement and possible risk contexts (comorbidities with cardiac risk, and high-risk medications) were also analysed. METHODS: Observational study with older adults (≥ 65 years) diagnosed with cancer, who were treated with antineoplastic agents (ANAs); it was conducted in three hospitals from the north of Portugal. Data collection was obtained using self-reports and medical records. DDIs were identified and classified using Micromedex® software. Descriptive and association analyze statistics were performed. Statistical hypothesis tests with p value less than 0.05 were considered significant. All statistical procedures and analysis were performed with R version 4.1.3. RESULTS: We enrolled 552 patients. Polypharmacy prevalence was 88.40%; 76.45% and 56.16% of the patients presented with DDIs and SDIs, respectively. SDIs with ANAs were found in 21.20% of the patients. High-risk medications were associated with a higher risk of polypharmacy, DDIs, and SDIs. Polypharmacy and DDIs were higher in patients with hypertension or diabetes. SDIs were higher in patients with diabetes. CONCLUSION: Polypharmacy, potential DDIs and SDIs were highly prevalent in older adults with cancer. A careful review of the medication administered is necessary to decrease it. These findings warrant further research to optimize medication in this population and decrease problems related to medication, which may lead to emergency room visits and hospitalisations, compromising patient safety and/or ongoing treatments.

Advancing perspectives on the off-label use of anticancer drugs: an updated classification and exploration of categories.

To date, the definition that the off-label usage of drugs refers to the unapproved use of approved drugs, which covers unapproved indications, patient populations, doses, and/or routes of administration, has been in existence for many years. Currently, there is a limited frequency and prevalence of research on the off-label use of antineoplastic drugs, mainly due to incomplete definition and classification issues. It is time to embrace new categories for the off-label usage of anticancer drugs. This review provided an insight into an updated overview of the concept and categories of the off-label use of anticancer drugs, along with illustrating specific examples to establish the next studies about the extent of the off-label usage of anticancer drugs in the oncology setting. The scope of the off-label use of current anticancer drugs beyond the previous definitions not only includes off-label uses in terms of indications, patient populations, doses, and/or routes of administration but also off-label use in terms of medication course, combination, sequence of medication, clinical purpose, contraindications scenarios, etc. In addition, the definition of the off-label usage of anticancer drugs should be added to the condition at a given time, and it varies from approval authorities. We presented a new and relatively comprehensive classification, providing extensive analysis and illustrative examples of the off-label usage of antineoplastic drugs for the first time. Such a classification has the potential to promote practical adoption and enhance management strategies for the off-label use of antitumor drugs.

[Older patients and injectable anticancer drug: Feasibility study of the implementation of pharmaceutical interviews in oncogeriatrics in a hospital center]. / Patients âgés et anticancéreux injectables : étude de faisabilité de la mise en place d'entretiens pharmaceutiques d'oncogériatrie dans un centre hospitalier.

INTRODUCTION: In our establishment, pharmaceutical interviews in oncogeriatrics have been developed to reduce drug iatrogenesis. The target patients were older patients (≥65years) with polypharmacy and/or identified at risk of frailty (G8≤14), starting an injectable cancer protocol. METHODS: The aim of this study is to evaluate the feasibility of implementing pharmaceutical interviews in oncogeriatrics over a period of six months. RESULTS: In total, 30 patients benefited from a pharmaceutical interview in oncogeriatrics (median age 76 years; 21 patients with G8≤14). Two-thirds of the patients met other interveners during patient care, 4 of whom after referral by the pharmacist. As for medication reviews: 93% of patients required pharmaceutical intervention (average of 3.5 per patient). The majority proposed therapeutic follow-ups and discontinuations of treatment. According to their evaluation by a pharmacist/oncologist pair, 97% of pharmaceutical interventions would have a positive clinical impact, of which 13 % a major clinical impact. The main drug classes concerned by the pharmaceutical interventions were analgesics, drugs used in diabetes and psycholeptics. Among the four pharmaceutical interventions with major clinical impact, nine proposed the optimization of analgesic treatment. DISCUSSION: The implementation of these interviews allowed us to initiate the creation of a care pathway dedicated to older patients identified as fragile. The pharmaceutical care offered appear to provide added value in the care of these patients. Organizational changes are necessary to promote multidisciplinarity and improve our practices in oncogeriatrics.

Potency and efficacy of pharmacological PIP4K2 inhibitors in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.

Oral herpes simplex virus infection in patients undergoing chemotherapy - an integrative review.

Aim: The purpose of this study is to undertake an integrative literature review in order to determine the prevalence, etiology, and reactivation of oral HSV infection in patients receiving chemotherapy (CT). Methods: The study was carried out in the PubMed/MEDLINE, Embase, Virtual Health Library, and Scopus databases, using the descriptors "Herpes Simplex", "Viral Diseases", "Mouth", and "Antineoplastic Agents". Results: The findings suggest that HSV infection is widespread in this group of patients and can be severe. HSV infection is frequent in CT patients, and treatment should begin as soon as it is feasible, utilizing antivirals to avoid future difficulties, as patients are immunocompromised. Conclusion: It is critical for health professionals to be fully informed on the dangers and treatment choices available, with the most appropriate therapy for each circumstance. Furthermore, more recent research with acceptable methodological rigor is required to better quantify the prevalence of HSV in these patients.

Comparison between Nivolumab and Regorafenib as Second-line Systemic Therapies after Sorafenib Failure in Patients with Hepatocellular Carcinoma.

PURPOSE: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. MATERIALS AND METHODS: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. RESULTS: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). CONCLUSION: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.

Role of transarterial chemoembolization for hepatocellular carcinoma with extrahepatic metastases in the era of advancing systemic therapy.

Background/Aims: Systemic therapy is the current standard treatment for hepatocellular carcinoma (HCC) with extrahepatic metastases (EHM). However, some patients with HCC and EHM undergo transarterial chemoembolization (TACE) to manage intrahepatic tumors. Herein, we aimed to explore the appropriateness of TACE in patients with HCC and EHM in an era of advanced systemic therapy. Methods: This study analyzed 248 consecutive patients with HCC and EHM (median age 58.5 years, 83.5% male, and 88.7% Child-Pugh A) who received TACE or systemic therapy (83 sorafenib, 49 lenvatinib, 28 immunotherapy-based) between January 2018 and January 2021. Results: Among the patients, 196 deaths were recorded during a median follow-up of 8.9 months. Patients who received systemic therapy had a higher albumin-bilirubin grade, elevated tumor markers, an increased number of intrahepatic tumors, larger-sized tumors, and more frequent portal vein invasion than those who underwent TACE. TACE was associated with longer median overall survival (OS) than sorafenib (15.1 vs. 4.7 months; 95% confidence interval [CI]: 11.1-22.2 vs. 3.7-7.3; hazard ratio [HR] 1.97, P<0.001). After adjustment for potential confounders, TACE was associated with statistically similar survival outcomes to those of lenvatinib (median OS: 8.0 months; 95% CI: 6.5-11.0; HR 1.21, P=0.411) and immunotherapies (median OS: 14.3 months; 95% CI: 9.5-27.0; HR 1.01, P=0.973), demonstrating survival benefits equivalent to these treatments. Conclusion: In patients with HCC and EHM, TACE can provide a survival benefit comparable to that of newer systemic therapies. Accordingly, TACE remains a valuable option in this era of new systemic therapies.

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.

[Box: see text].

Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin.

OBJECTIVE: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION: During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

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.

Optimal management of radiation pneumonitis: Findings of an international Delphi consensus study.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) for lung cancer, however, the optimal practice for diagnosis, management, and follow-up for RP remains unclear. We thus sought to establish expert consensus recommendations through a Delphi Consensus study. METHODS: In Round 1, open questions were distributed to 31 expert clinicians treating thoracic malignancies. In Round 2, participants rated agreement/disagreement with statements derived from Round 1 answers using a 5-point Likert scale. Consensus was defined as ≥ 75 % agreement. Statements that did not achieve consensus were modified and re-tested in Round 3. RESULTS: Response rate was 74 % in Round 1 (n = 23/31; 17 oncologists, 6 pulmonologists); 82 % in Round 2 (n = 19/23; 15 oncologists, 4 pulmonologists); and 100 % in Round 3 (n = 19/19). Thirty-nine of 65 Round 2 statements achieved consensus; a further 10 of 26 statements achieved consensus in Round 3. In Round 2, there was agreement that risk stratification/mitigation includes patient factors; optimal treatment planning; the basis for diagnosis of RP; and that oncologists and pulmonologists should be involved in treatment. For uncomplicated radiation pneumonitis, an equivalent to 60 mg oral prednisone per day, with consideration of gastroprotection, is a typical initial regimen. However, in this study, no consensus was achieved for dosing recommendation. Initial steroid dose should be administered for a duration of 2 weeks, followed by a gradual, weekly taper (equivalent to 10 mg prednisone decrease per week). For severe pneumonitis, IV methylprednisolone is recommended for 3 days prior to initiating oral corticosteroids. Final consensus statements included that the treatment of RP should be multidisciplinary, the uncertainty of whether pneumonitis is drug versus radiation-induced, and the importance risk stratification, especially in the scenario of interstitial lung disease. CONCLUSIONS: This Delphi study achieved consensus recommendations and provides practical guidance on diagnosis and management of RP.