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BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigators choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

CONTEXT: Next-generation sequencing (NGS) analysis of sporadic medullary thyroid carcinoma (sMTC) has led to increased detection of somatic mutations, including RET M918T, which has been considered a negative prognostic indicator. OBJECTIVE: This study aimed to determine the association between clinicopathologic behavior and somatic mutation identified on clinically motivated NGS. METHODS: In this retrospective cohort study, patients with sMTC who underwent NGS to identify somatic mutations for treatment planning were identified. Clinicopathologic factors, time to distant metastatic disease (DMD), disease-specific survival (DSS), and overall survival (OS) were compared between somatic mutations. RESULTS: Somatic mutations were identified in 191 sMTC tumors, including RET M918T (53.4%), other RET codons (10.5%), RAS (18.3%), somatic RET indels (8.9%), and RET/RAS wild-type (WT) status (8.9%). The median age at diagnosis was 50 years (range, 11-83); 46.1% were female. When comparing patients with RET M918T, RET-Other, and RET WT (which included RAS and RET/RAS WT), there were no differences in sex, TNM category, systemic therapy use, time to DMD, DSS, or OS. On multivariate analysis, older age at diagnosis (HR 1.05, P < .001; HR 1.06, P< .001) and M1 stage at diagnosis (HR 3.17, P = .001; HR 2.98, P = .001) were associated with decreased DSS and OS, respectively, but mutation cohort was not. When comparing RET M918T to RET indels there was no significant difference in time to DMD, DSS, or OS between the groups. CONCLUSION: Somatic RET mutations do not portend compromised DSS or OS in a cohort of sMTC patients who underwent clinically motivated NGS.

BACKGROUND: Half of countries in Africa lack access to radiation (RT), which is essential for standard treatment of locally advanced cervical cancers. We evaluated outcomes for patients treated with neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in settings where no RT is available. METHODS: We performed a retrospective descriptive study of all patients with FIGO stage IB2-IIA2 and some exceptional stage IIB cases who received NACT and surgery at Kigali University Teaching Hospital in Rwanda. Patients were treated with NACT consisting of carboplatin and paclitaxel once every 3 weeks for 3-4 cycles before radical hysterectomy. We calculated recurrence rates and overall survival (OS) rate was determined by Kaplan-Meier estimates. RESULTS: Between May 2016 and October 2018, 57 patients underwent NACT and 43 (75.4%) were candidates for radical hysterectomy after clinical response assessment. Among the 43 patients who received NACT and surgery, the median age was 56 years, 14% were HIV positive, and FIGO stage distribution was: IB2 (32.6%), IIA1 (7.0%), IIA2 (51.2%) and IIB (9.3%). Thirty-nine (96%) patients received 3 cycles and 4 (4%) received 4 cycles of NACT. Thirty-eight (88.4%) patients underwent radical hysterectomy as planned and 5 (11.6%) had surgery aborted due to grossly metastatic disease. Two patients were lost to follow up after surgery and excluded from survival analysis. For the remaining 41 patients with median follow-up time of 34.4 months, 32 (78%) were alive with no evidence of recurrence, and 8 (20%) were alive with recurrence. One patient died of an unrelated cancer. The 3-year OS rate for the 41 patients who underwent NACT and surgery was 80.8% with a recurrence rate of 20%. CONCLUSIONS: Neoadjuvant chemotherapy with radical hysterectomy is a feasible treatment option for locally advanced cervical cancer in settings with limited access to RT. With an increase in gynecologic oncologists skilled at radical surgery, this approach may be a more widely available alternative treatment option in countries without radiation facilities.

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

BACKGROUND: By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (

BACKGROUND: Shortness of breath occurs in 10%-70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. METHODS: Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as well as a joint analysis using severity AND distress ratings. Differences among the latent classes were evaluated using parametric and nonparametric tests. RESULTS: For severity, two classes were identified (Slight to Moderate [91.6%] and Moderate to Severe [8.4%]). For distress, two classes were identified (A Little Bit to Somewhat [83.9%] and Somewhat to Quite a Bit [16.1%]). For the joint LPA, two classes were identified (Lower Severity and Distress [79.9%] and Higher Severity and Distress [20.1%]). While distinct risk factors were associated with each of the LPAs, across the three LPAs, the common risk factors associated with membership in the worse class included: a past or current history of smoking, poorer functional status, and higher comorbidity burden. In addition, these patients had a higher symptom burden and higher levels of cancer-specific stress. CONCLUSIONS: Clinicians can use the information provided in this study to identify high-risk patients and develop individualized interventions.

PURPOSE: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.

BACKGROUND: Equine herpes virus type 1 (EHV-1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. REVIEW QUESTION: Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV-1 in domesticated horses? METHODS: A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV-1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV-1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions. RESULTS: A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis-based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested. CONCLUSIONS AND CLINICAL IMPORTANCE: Our review indicates minimal or limited benefit either as a prophylactic or post-exposure treatment for any of the studied interventions in the mitigation of EHV-1-associated disease outcome.

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

PURPOSE: We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC). METHODS: Patients with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m2 and cyclophosphamide 600 mg/m2, and dose level 1 was defined as eribulin 1.4 mg/m2 and cyclophosphamide 600 mg/m2. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33-82 years), 1 prior line of hormone therapy (range 0-6), and 2 prior lines of chemotherapy (range 0-7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8-21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8-21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive ([Formula: see text] 5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011). CONCLUSION: In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.

Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB‐positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG‐ALL‐2015 and CCCG‐ALL‐2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Results: Pediatric PDGFRB‐positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B‐ALL and 4 T‐ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31‐33 abnormalities, and one suffered from a complex karyotype. The 3‐year event‐free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow‐up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine‐kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p <.05). Conclusions: Pediatric PDGFRB‐positive ALL has a poor outcome associated with high‐risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Plain Language Summary: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high‐risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse.Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive acute lymphoblastic leukemia (ALL) patients.The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. Pediatric acute lymphoblastic leukemia (ALL) patients with PDGFRB fusions are associated with high‐risk clinical features. Chemotherapy plus tyrosine‐kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB‐positive ALL patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB‐positive ALL patients. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone‐sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow‐up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan–Meier methods estimated overall survival (OS) and castration‐resistant prostate cancer (CRPC)‐free survival from mHSPC diagnosis date and a log‐rank test compared these outcomes by oligometastatic status. Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non‐omHSPC had higher median prostate‐specific antigen at diagnosis (151.7) than omHSPC (44.1). First‐line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non‐omHSPC (14%). More omHSPC patients received metastasis‐directed therapy/prostate radiation therapy (14%) versus non‐omHSPC (2%). Median OS and CRPC‐free survival (in months) were higher in omHSPC versus non‐omHSPC (44.4; 95% confidence interval [CI], 33.9–not estimated vs. 26.2; 95% CI, 20.5–32.5, p =.0089 and 27.6; 95% CI, 22.1–37.2 vs. 15.3; 95% CI, 12.8–17.9, p =.0049), respectively. Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non‐omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non‐omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies. In this observational retrospective Veterans Affairs cohort study, 20% of men had de novo oligometastatic hormone‐sensitive prostate cancer (omHSPC). Although first‐line (1L) novel hormonal therapy was similar between groups, 1L chemotherapy use was lower in omHSPC, more omHSPC patients received metastasis‐directed therapy/prostate radiation therapy, and median overall survival and time to castration resistance was longer in men with omHSPC than non‐omHSPC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Comprehensive analysis of novel treatment modalities for Glioblastoma (GBM). • Role of nanocarriers in addressing limitations with conventional GBM therapeutics. • Updates of clinical landscape of novel GBM therapeutics. • Limitations with novel nanoparticles approach in GBM therapeutics. Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood–brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation. [ABSTRACT FROM AUTHOR]

Purpose: The National Comprehensive Cancer Network (NCCN) guidelines recommend a variety of drug combinations with specific administration schedules for the treatment of early-stage breast cancer, allowing physicians to deliver treatments recognizing individual patient complexities, including comorbidities, and patient-physician preference. While use of guideline regimens has shifted over time, there is little data to describe changes in how treatment for early-stage breast cancer has evolved over time. Methods: In a cohort of 34,109 women treated for stage I-IIIA breast cancer between 2006–2019 at Kaiser Permanente Northern California and Kaiser Permanente Washington, we present the changes in chemotherapy regimens over time, and explore use of NCCN-guideline regimens (GR), guideline regimens used when said regimens were not included in guidelines, referred to as time-discordant regimens (TDR), and non-guideline regimens (NGR). Results are presented by drug combination and over time. Results: Among 12,506 women receiving chemotherapy, 77.4% (n = 9681) received GRs, 9.1% (n = 1140) received TDRs, and 13.5% (n = 1685) received NGRs. In 2006, AC-T (cyclophosphamide-doxorubicin, paclitaxel) was the most common regimen, with TC (cyclophosphamide-docetaxel) becoming the most prevalent by 2019. NGRs were more common in cyclophosphamide-methotrexate-5-fluorouracil (CMF); cyclophosphamide-doxorubicin-paclitaxel-trastuzumab (ACTH); and paclitaxel-trastuzumab (TH). The use of GR has increased over time (p-trend < 0.001), while use of NGR (both in terms of administration schedule and drug combination) and TDR have decreased, although patterns vary by drug combination. Conclusion: Chemotherapy delivery has changed markedly over time, with a move toward more use of GR. These data are important for understanding the landscape of chemotherapy delivery in community healthcare settings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lung cancer is one of the most common malignant tumors with the worst prognosis worldwide. Its incidence rate and mortality rate have long been among the top of malignant tumors. The heterogeneity and drug resistance are among the reasons contributing to its poor prognosis. Lung cancer organoid, which is a 3D in vitro model cultured from patient-derived tumor cells recapitulating the biological characteristics of the primary tumor, can be used for various researches of lung cancer. OBJECTIVE: To review the application and research progress of lung cancer organoids in chemotherapy, targeted therapy, and immunotherapy drug sensitivity screening, analyze its limitations, aiming to provide new strategies for personalized and precision medicine of lung cancer. METHODS: The first author searched relevant articles published from 2013 to 2023 in CNKI and PubMed in July 2023. The search terms were “organoid, lung cancer organoid, lung cancer experimental model, precision medicine, drug sensitivity test, chemotherapy, targeted therapy, immunotherapy” in Chinese and English. Finally, a total of 84 articles were incorporated. RESULTS AND CONCLUSION: (1) Compared with traditional lung cancer research models, which can only demonstrate two-dimensional cell activities, lack cell-to-cell interactions, and suffer from species differences, lung cancer organoids offer a diverse cell source and continuously optimized culture conditions. They can simulate cellular interactions in a three-dimensional context while retaining the biological characteristics of the original tumor. These organoids represent a promising research model with significant potential, providing a solid foundation for their use in cancer drug screening. (2) Lung cancer organoids have shown preliminary significance in guiding anticancer drug selection. Their predictive outcomes align closely with actual clinical outcomes, marking a pivotal step towards precision in lung cancer treatment. By assessing the efficacy of common chemotherapy, targeted therapy, and immunotherapy drugs, these organoids enable the customization of individualized treatment strategies, reducing unnecessary drug trials and toxic and side reaction while exploring possible alternative drugs or combination regimens for drug resistance issues so as to guide the precision treatment of rare mutated lung cancer and fill the clinical gap. A more comprehensive drug evaluation is provided by comparing the activity of different drugs. Additionally, it is essential to consider the internal heterogeneity of organoids, emphasizing the importance of multiple sampling to enhance result accuracy. (3) Lung cancer organoids have limitations in practical applications such as inconsistent success rates and purity in cultivation and the lack of vascular tissue. To address these shortcomings, improvements are needed in cultivation conditions, expedited testing processes, and the development of multi-organ systems to simulate the overall effects of drugs in multiple organs. These enhancements will contribute to a more accurate assessment of drug efficacy and toxicity, thereby enhancing the precision of lung cancer treatment. [ABSTRACT FROM AUTHOR]

Aim: Assess factors associated with first-line (1L) treatment for HR+/HER2- metastatic breast cancer. Materials & methods: A cross-sectional survey of 250 US oncologists was conducted. Correlations were calculated between treatment class and demographics, treatment perceptions and other clinical/nonclinical characteristics. Results: Efficacy and safety/tolerability were critical in oncologists' 1L decision-making. CDK4/6i use positively correlated with proportion of Medicare and postmenopausal patients (r = 0.54–0.67). Chemotherapy use demonstrated positive correlations with perimenopausal and premenopausal patients and symptom burden (r = 0.31–0.42). Aromatase inhibitor (AI) monotherapy correlated positively with anticipated treatment compliance (r = 0.42). Conclusion: Efficacy and safety/tolerability were most important to 1L decision-making. Clinical characteristics corresponded with CDK4/6i and chemotherapy use. Anticipated compliance was associated with AI monotherapy use. Plain Language Summary Patients in the USA with a certain type of metastatic breast cancer (mBC, i.e., HR+/HER2−) might get chemotherapy or hormone therapy alone instead of new and potentially better medicines called cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as their first treatment. Researchers wanted to understand how US cancer specialists decided the first treatment for this type of mBC. In a survey of 250 cancer specialists, researchers looked at different factors that might influence decision-making, including patient characteristics, doctors' opinions about the treatments and other medical and non-medical features. This study also examined the connections between these factors and the cancer specialists' choice of first treatment. Researchers found that cancer specialists care most about how well a treatment works and how safe it is when choosing the first treatment for HR+/HER2− mBC. They are more likely to use CDK4/6i if their patients have Medicare coverage or are older (i.e., women who have been through menopause). Chemotherapy is chosen if their patients are younger (i.e., women who are near and before menopause) or have more symptoms. Cancer specialists tend to choose first treatment with hormone therapy alone if they think their patients have a hard time following their treatment plan. The results showed that patient characteristics, doctors' opinions of treatments and other medical and non-medical factors play a role in choosing treatment for HR+/HER2− mBC. By understanding these factors, researchers can work toward improving treatment choices for patients with this type of mBC. Tweetable Abstract US #oncologists consider efficacy and safety as most important when selecting first-line treatment for #HR+/HER2− #metastaticbreastcancer. Different patient characteristics correlated with greater selection of #aromataseinhibitors, #chemotherapy and #CDK4/6inhibitors. Article highlights Breast cancer (BC) is the most prevalent cancer globally, with 6% of women in the USA diagnosed with de novo metastatic disease. HR+/HER2− is the most common BC subtype, accounting for 87.4 new cases per 100,000 women. Endocrine therapy (ET) was traditionally preferred for HR+/HER2− metastatic disease (mBC), until recent therapeutic advances introduced cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with ET. Current guidelines recommend CDK4/6i+ET as the preferred first-line (1L) treatment, with approximately 60–63% adoption in routine US clinical practice. Findings from this study highlight that US oncologists prioritize anticipated treatment efficacy and safety/tolerability in 1L treatment decisions. Patient demographics, clinical characteristics and nonclinical factors are also considerations in treatment decisions. Factors positively correlated with higher CDK4/6i use include a higher proportion of postmenopausal patients, Medicare coverage and emphasis on treatment efficacy and performance status. Increased chemotherapy use in the 1L setting is correlated with higher proportions of premenopausal and perimenopausal patients, along with an emphasis on symptom burden. Factors associated with higher aromatase inhibitor (AI) monotherapy use include greater consideration of expected lack of treatment compliance, a higher proportion of perimenopausal patients and reliance on health insurance marketplace/state exchange coverage. Oncologists perceive CDK4/6i+ET as the appropriate 1L treatment, while chemotherapy is considered for patients with a high symptom burden and AI monotherapy is chosen when tolerability is a concern. [ABSTRACT FROM AUTHOR]

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p‐glycoprotein (P‐gp) mediated drug efflux is one of the primary causes, the development of P‐gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P‐gp exists in many tissues, the non‐selective P‐gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P‐gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P‐gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post‐modification, various benzofuran‐fused‐piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P‐gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA‐MB‐231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy. [ABSTRACT FROM AUTHOR]

Background: Nivolumab + chemotherapy is now a standard of care for HER2-negative, previously untreated, unresectable or recurrent gastric/gastroesophageal junction cancer (advanced gastric cancer), but long-term follow-up data of clinical trials are limited. Methods: ATTRACTON-4 was a phase 3, double-blind, placebo-controlled trial in Japan, South Korea, and Taiwan. Patients were randomized to either nivolumab or placebo, both combined with the physician's choice of SOX (oral S-1 [tegafur–gimeracil–oteracil potassium] + oxaliplatin) or CAPOX (capecitabine + oxaliplatin). We report the primary endpoints—centrally assessed progression-free survival (PFS) and overall survival (OS)—and landmark analyses of OS among patients alive using 3-year follow-up data. Results: At the cutoff date (May 10, 2021), 17/359 patients in the nivolumab + chemotherapy group and 6/358 in the placebo + chemotherapy group were continuing study treatment. PFS (centrally assessed) was longer in the nivolumab + chemotherapy group (median 10.94 vs. 8.48 months; hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.55–0.82). Although OS did not differ between the two groups (median 17.45 vs. 17.15 months; HR 0.89, 95% CI 0.75–1.05), the landmark analysis of OS, calculating HRs at each landmark time point (every month), was getting numerically better in the nivolumab + chemotherapy group over time. Approximately 80% of patients who achieved complete response in the nivolumab + chemotherapy group were alive at 3 years. No new safety signals or major late-onset select treatment-related adverse events were observed for nivolumab + chemotherapy. Conclusion: This 3-year follow-up of ATTRACTION-4 confirmed the long-term clinical benefit and manageable safety of nivolumab + chemotherapy in patients with previously untreated advanced gastric cancer. Trial registration: NCT02746796 [ABSTRACT FROM AUTHOR]

Background: Olanzapine is prescribed as prophylaxis for chemotherapy-induced nausea and vomiting at a dose of 2.5 or 5 mg in Asian countries. We compared the effectiveness of olanzapine 2.5 mg and 5 mg in preventing chemotherapy-induced nausea and vomiting among patients receiving high-emetogenic chemotherapy for lung cancer. Methods: Using a Japanese national inpatient database, we identified patients who received olanzapine doses of 2.5 or 5 mg during high-emetogenic chemotherapy for lung cancer between January 2016 and March 2021. We conducted a 1:1 propensity score-matched analysis with adjustment for various factors, including those affecting olanzapine metabolism. The outcomes were additional antiemetic drug administration (within 2–5 days after chemotherapy initiation), length of hospital stay, and total hospitalization costs. Results: Olanzapine 2.5 and 5.0 mg were used in 2905 and 4287 patients, respectively. The propensity score-matched analysis showed that olanzapine 2.5 mg administration was significantly associated with a higher proportion of additional antiemetic drug administration (36% vs. 31%, p < 0.001) than olanzapine 5 mg. The median length of hospital stay was 8 days in both groups. Total hospitalization cost did not differ significantly between the two doses of olanzapine (5061 vs. 5160 USD, p = 0.07). The instrumental variable analysis demonstrated compatible results. Conclusion: Prophylactic use of olanzapine 2.5 mg during chemotherapy for lung cancer was associated with a higher rate of additional antiemetic drugs than olanzapine 5 mg. [ABSTRACT FROM AUTHOR]

Objective: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). Method: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. Results: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. Conclusion: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence. [ABSTRACT FROM AUTHOR]

Background: AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS. Setting: People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries. Methods: We estimated mortality rates over the trial period. Cox proportional hazards regressions were used to identify baseline characteristics associated with mortality and compared mortality rates between participants who had KS progression within 12 weeks of treatment initiation (early progression of KS [KS-PD]) and those who did not. Results: Of the 329 and 189 eligible participants in A5263/ AMC066 and A5264/AMC067, 71 (21.6%) and 24 (12.7%) died, respectively. In both trials, hypoalbuminemia was associated with increased hazards of death compared with normal albumin; A5263/ AMC066: mild hypoalbuminemia (adjusted hazard ratio [aHR] = 3.01; 95% CI: 1.42 to 6.29), moderate hypoalbuminemia (aHR = 5.11; 95% CI: 2.54 to 10.29), and severe hypoalbuminemia (aHR = 14.58; 95% CI: 6.32 to 35.60), and A5264/AMC067: mild hypoalbuminemia (aHR = 5.66; 95% CI: 1.90 to 16.93) and moderate hypoalbuminemia (aHR = 7.02; 95% CI: 2.57 to 19.15). The rate of death was higher among participants who had early KSPD than those without early KS-PD in A5263/AMC066 (HR = 5.09; 95% CI: 1.71 to 15.19) but not in A5264/AMC067 (HR = 1.74; 95% CI: 0.66 to 4.62). Conclusions: Albumin measurements may be used to identify individuals at higher risk of death after initiating KS treatment and for evaluation of interventions that can reduce AIDS-KS mortality. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with overt or occult hepatitis B virus (HBV) infection receiving immunosuppressive treatments have a wide risk of HBV reactivation (HBVr). We performed meta‐analysis with decision curve analyses (DCA) to estimate the risk of HBVr in HBsAg‐negative anti‐HBc‐positive patients naïve to nucleos(t)ide analogues (NAs) receiving immunosuppressive treatments. Approach and Results: Studies were identified through literature search until October 2022. Pooled estimates were obtained using random‐effects model. Subgroup analyses were performed according to underlying disease and immunosuppressive treatments. DCA was used to identify the threshold probability associated with the net benefit of antiviral prophylaxis in HBsAg‐negative anti‐HBc‐positive patients. We selected 68 studies (40 retrospective and 28 prospective), including 8034 patients with HBsAg negative anti‐HBc positive. HBVr was 4% (95% CI 3%–6%) in HBsAg‐negative anti‐HBc‐positive patients, with a significantly high heterogeneity (I2 69%; p <.01). The number‐needed‐to‐treat (NNT) by DCA ranged from 8 to 24 for chemotherapy plus rituximab, from 12 to 24 for targeted therapies in cancer patients and from 13 to 39 for immune‐mediated diseases. Net benefit was small for monoclonal antibodies. Conclusions: Our DCA in HBsAg‐negative anti‐HBc‐positive patients provided evidence that NA prophylaxis is strongly recommended in patients treated with chemotherapy combined with rituximab and could be appropriate in patients with cancer treated with targeted therapies and in patients with immune‐mediated diseases. Finally, in patients with cancer treated with monoclonal antibodies or with chemotherapy without rituximab, the net benefit is even lower. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) of the liver represent a rare entity. Amongst this group of uncommon diseases primary hepatic neuroendocrine neoplasm (PH‐NEN) represent only 0.3% of all NENs. Moreover, PH‐NEN has very rarely been reported in pregnancy. We report a 28‐year‐old young patient with metastatic small cell neuroendocrine carcinoma of the liver complicated with pregnancy. She was evaluated and managed through a multidisciplinary team approach and received two cycles of chemotherapy with a cisplatin/etoposide regimen during the antenatal period and delivered at 37 weeks period of gestation (POG). This case highlights the importance of major challenges faced during the diagnosis and management of this very rare disease in pregnancy and the successful fetomaternal outcome. Synopsis: Primary hepatic neuroendocrine neoplasms (PH‐NENs) constitute 0.3% of all NENs, and are rarely reported in pregnancy. A 28‐year‐old pregnant woman was managed successfully, emphasizing diagnostic and management challenges. [ABSTRACT FROM AUTHOR]

Thymic carcinoma (TC) is a rare form of highly invasive tumors. Currently, the standard first-line therapy involves paclitaxel plus carboplatin treatment, while the recommended regimen for second-line therapy remains uncertain. The purpose of this study is to explore the second-line mode of TC patients. We evaluated the outcome of subjects with advanced TC between 2009 and 2023 in three medical centers, retrospectively. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Kaplan-Meier was used for calculating Progression-free survival (PFS) and overall survival (OS). The factors affecting survival in the real world were evaluated by Cox analysis. Totally 136 patients were included in this study, the median PFS (mPFS) for all subjects was 5.97 months, and the median OS (mOS) was 25.03 months. According to patient's treatment modes, they are divided into monotherapy (n = 95) and combination therapy (n = 41), PFS manifested the difference between two groups (5.17 vs. 9.00 months, P = 0.043). OS also indicated a significant distinction (22.50 vs. 38.00 months, P = 0.017). Furthermore, there was a significant difference in PFS between patients using immunotherapy combined with chemotherapy and those with antivascular therapy (8.57 vs. 13.10 months, P = 0.047). In the second-line therapy for advanced TC, the efficacy of combination therapy was better than monotherapy, especially for immunotherapy combined with antivascular therapy. • One hundred and thirty-six patients were enrolled, including 95 patients with monotherapy and 41 with combination therapy. • The efficacy of combination therapy was better than that of monotherapy. • Immunotherapy combined with anti-angiogenesis therapy showed better efficacy in second-line TC patients. [ABSTRACT FROM AUTHOR]

introduction: This study aimed to study the potential effects of oxaliplatin-based chemotherapy on cardiorespiratory fitness, handgrip strength (HGS), body composition, and quality of life (QoL) of stages III–IV colorectal cancer (CRC) patients before the first cycle (T0) and after the last cycle of systemic adjuvant/neoadjuvant chemotherapy (T1). Methods: Cardiorespiratory fitness, HGS, body composition, and QoL were evaluated with the six-minute walk test (6MWT), hydraulic hand dynamometer, body composition analyzer, and Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire in both T0 and T1, respectively. Results: Twenty-eight CRC patients were included in this study. The total walked distance (TWD) was found to be decreased from T0 to T1 (499.72 m vs. 488.56 m); however, this change was not significant (z = -.706, p = 0.48). Type of chemotherapy whether adjuvant or neoadjuvant also showed no significant effect on TWD (z = -.1.372, p =.17 vs z = -1.180, p =.238, respectively). The QoL was significantly decreased (T0 = 118.35 vs T1 = 110.77, t = 2.176,p = 0.05). The TWD was significantly correlated with the physical well-being (PWB) subscale of FACT-C (r =.64, p = 0.001) as well as with HGS (r =.46, p =.018) in T0. After controlling for age, type of chemotherapy, and type of regimen, the HGS did not show a significant difference from T0 to T1 (F(1,23) = 1.557, p =.22, ηp2 =.06). However, the effect of time x gender showed significant difference from T0 to T1 (F(1,23) = 4.906, p =.037, ηp2 =.17). Conclusion: This study showed the decreased QoL and physical well-being of CRC patients who underwent oxaliplatin-based treatment. In addition, the gender effect of decreased HGS should be considered further when planning an oncological rehabilitation program. [ABSTRACT FROM AUTHOR]

Background: There is interest in using bladder-preserving therapy as an alternative definitive therapy for muscle invasive bladder cancer in certain high-risk groups such as the elderly. Objective: To determine if bladder-preserving therapy represents a safer alternative to surgical intervention in elderly patients with muscle invasive bladder cancer. Methods: We surveyed the Surveillance, Epidemiology and End Results database (SEER) for cases of non-metastasized malignant bladder cancer in patients aged 80+. Survival outcomes with radical cystectomy (RC) with or without chemotherapy were compared to those after chemotherapy and radiation without cystectomy. We performed log-rank tests and Kaplan-Meier and cox regression and hazard analyses before and after propensity score matching. Results: A total of 2995 patients were identified, with 49.98% treated with RC only, 8.65% treated with RC/chemotherapy, and 41.37% treated with chemotherapy and radiation without RC. Median overall survival for the RC only, RC/chemotherapy and chemotherapy/radiation groups were 31.4, 44.1, and 24.6 months, respectively. On multivariate analysis, hazard ratios (reference: RC/chemotherapy group) were RC Only (HR = 1.408 (95% CI 1.188–1.669), p < 0.0001) and chemotherapy/radiation (HR = 1.650 (95% CI 1.390–1.959), p < 0.0001). After matching the chemotherapy/radiation and RC/chemotherapy groups, the former continued to show survival hazard (HR = 1.744 (95% CI 1.414–2.155), p < 0.0001). Conclusions: Octogenarians should be offered definitive local therapy for their localized bladder cancer including RC and chemotherapy. Bladder-sparing alternatives should be reserved for patients unfit for surgery. [ABSTRACT FROM AUTHOR]

Objectives: Bladder-Sparing Approach was presented in patients who are not willing or not suitable for Radical Cystectomy (RC). There have been inconsistencies in the literature regarding the comparison of survival rates of these two methods. Our objective is to evaluate the survival rate of patients with muscle-invasive bladder cancer (MIBC) undergoing different treatment methods. Design: Retrospective cross-sectional study. Setting: A secondary care, multicenter study in Kerman, Iran 2008 to 2016. Participants: All 200 patients who were diagnosed with Muscle Invasive Bladder Cancer and were admitted to our hospitals. Patients with inaccessible medical files and patients with pathologies other than TCC were excluded. Main outcome measures: Radical cystectomy and different methods of bladder preservation were compared based on their survival rate. Interventions: Radical cystectomy or bladder preservation Results: Overall survival of the patients was 2 years [95% CI: 1.37–2.63]. The overall 5-year survival rate of patients with MIBC was 32%. Having a 6.4 years overall survival, the RC group showed the highest survival compared with others (p = 0.01); the overall survival of patients undergoing TMT, TURT, chemotherapy, or radiotherapy monotherapy was 3.15 years [95% CI: 2.242–4.061], 4.06 [95% CI: 3.207–4.931], 2.58 [95% CI: 1.767–3.399], and 3.14 [95% CI: 1.614–4.672] years, respectively. Patients younger than 65 undergoing RC had an overall survival of 7 years, compared with 2 years for the TMT group. (p = 0.0001). Conclusions: The Bladder-Preservation method, as a replacement for RC, showed a lower overall survival rate in our study. A prospective randomized clinical trial may declare the best treatment. [ABSTRACT FROM AUTHOR]

This study explores the critical role of inhibitors targeting the mammalian target of rapamycin (mTOR) signaling pathway in breast cancer research and treatment. The mTOR pathway, a central regulator of cellular processes, has been identified as a crucial factor in the development and progression of breast cancer. The essay explains the complex molecular mechanisms through which mTOR inhibitors, such as rapamycin and its analogs, exert their anticancer effects. These inhibitors can stop cell growth, proliferation, and survival in breast cancer cells by blocking critical signaling pathways within the mTOR pathway. Furthermore, the essay discusses the implications of using mTOR inhibitors as a comprehensive therapeutic strategy. It emphasizes the potential benefits of combining mTOR inhibitors with other treatment approaches to enhance the effectiveness of breast cancer treatment. The evolving landscape of breast cancer research underscores the significance of mTOR as a therapeutic target and highlights ongoing efforts to improve and optimize mTOR inhibitors for clinical use. In conclusion, the essay asserts that inhibitors of the mTOR signaling pathway offer a promising approach in the fight against breast cancer. These inhibitors provide a focused and effective intervention targeting specific dysregulations within the mTOR pathway. As research advances, the integration of mTOR inhibitors into customized combination therapies holds excellent potential for shaping a more effective and personalized approach to breast cancer treatment, ultimately leading to improved outcomes for individuals affected by this complex and diverse disease. [ABSTRACT FROM AUTHOR]

Cancer drug resistance poses a significant obstacle to successful chemotherapy, primarily driven by the activity of ATP‐binding cassette (ABC) transporters, which actively efflux chemotherapeutic agents from cancer cells, reducing their intracellular concentrations and therapeutic efficacy. Recent studies have highlighted the pivotal role of long noncoding RNAs (lncRNAs) in regulating this resistance, positioning them as crucial modulators of ABC transporter function. lncRNAs, once considered transcriptional noise, are now recognized for their complex regulatory capabilities at various cellular levels, including chromatin modification, transcription, and post‐transcriptional processing. This review synthesizes current research demonstrating how lncRNAs influence cancer drug resistance by modulating the expression and activity of ABC transporters. lncRNAs can act as molecular sponges, sequestering microRNAs that would otherwise downregulate ABC transporter genes. Additionally, they can alter the epigenetic landscape of these genes, affecting their transcriptional activity. Mechanistic insights reveal that lncRNAs contribute to the activity of ABC transporters, thereby altering the efflux of chemotherapeutic drugs and promoting drug resistance. Understanding these interactions provides a new perspective on the molecular basis of chemoresistance, emphasizing the regulatory network of lncRNAs and ABC transporters. This knowledge not only deepens our understanding of the biological mechanisms underlying drug resistance but also suggests novel therapeutic strategies. In conclusion, the intricate interplay between lncRNAs and ABC transporters is crucial for developing innovative solutions to combat cancer drug resistance, underscoring the importance of continued research in this field. [ABSTRACT FROM AUTHOR]

[Display omitted] • Early life exposure to cisplatin induces TRPV1 and nociceptor sensitisation. • Cisplatin alters the developmental trajectory of nociceptors to be TrkA dependent. • Cisplatin induced survivorship pain is dependent upon TrkA signalling. Cisplatin-based chemotherapy is a common treatment for paediatric cancer. Unfortunately, cisplatin treatment causes neuropathic pain, a highly prevalent adverse health related complication in adult childhood cancer survivors. Due to minimal understanding of this condition, there are currently no condition tailored analgesics available. Here we investigated an alteration in nociceptor maturation that results in neuronal sensitisation and manifestation of cisplatin induced survivorship pain in a TrkA dependent manner. Cisplatin was administered (i.p. 0.1 mg/kg Postnatal day 14 and 16) to neonatal male and female Wistar rats and nociceptive behavioural assays were performed. In vitro studies utilised isolated neonatal dorsal root ganglia sensory neurons treated with cisplatin (5 μg/ml) to elucidate impact upon nociceptor activation and neurite growth, in combination with TrkA inhibition (GW441756 10 nM and 100 nM). Cisplatin treated male and female neonatal Wistar rats developed a delayed but lasting mechanical and heat hypersensitivity. Cisplatin administration led to increased TrkA expression in dorsal root ganglia sensory neurons. Nerve growth factor (NGF) induced TrkA activation led to sensory neuritogenesis and nociceptor sensitisation, which could be prevented through pharmacological TrkA inhibition (GW441756 either s.c. 100 nM or i.p. 2 mg/kg). Administration of TrkA antagonist suppressed cisplatin induced TRPV1 mediated nociceptor sensitisation and prevented cisplatin induced neuropathic pain. These studies provide greater understanding of the underlying mechanisms that cause cisplatin induced childhood cancer survivorship pain and allowing identification of potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival. [ABSTRACT FROM AUTHOR]

Enfortumab vedotin (EV), a nectin‐4‐binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV‐induced cutaneous eruption. A 58‐year‐old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV‐induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV‐induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV‐induced eruption, which may inform dermatologic and oncologic management. [ABSTRACT FROM AUTHOR]

Collecting duct carcinoma (CDC) is a rare disease associated with a high mortality rate. The present study describes the case of a recipient of a kidney transplant with metastatic allograft CDC whose treatment was successful. The patient underwent nephrectomy, and chemotherapy with gemcitabine and cisplatin, while undergoing haemodialysis treatment and remained in remission after 6 years of follow-up. There is a lack of information about the treatment and clinical management of CDC; however, the combination of gemcitabine and cisplatin remains as first-line therapy. The challenge of this case was integrating chemotherapy sessions with dialysis therapy to maintain the effectiveness, tolerability and safety of the oncological treatment. In the present case report, the success of chemotherapy with gemcitabine and cisplatin was demonstrated in a metastatic renal allograft CDC in a patient with end-stage renal disease, with few side effects and no recurrence of the disease 6 years after the end of treatment. [ABSTRACT FROM AUTHOR]

Ovarian serous carcinoma is a gynecological malignancy associated with a high mortality rate, which is commonly diagnosed in the first instance at a late stage and has a propensity to develop resistance to platinum-based chemotherapy. Identifying reliable biomarkers for platinum sensitivity is critical for improving patient outcomes. The present retrospective study included 64 patients with high-grade serous ovarian carcinoma (Federation of Gynecology and Obstetrics stages III or IV). Patients were classified as platinum-sensitive (no relapse within 6 months of the last platinum administration) or platinum-resistant (relapse within 6 months). Immunohistochemical analysis was performed to evaluate Fyn expression in tumor tissues, and Fyn knockdown experiments were performed using the OVSAHO ovarian cancer cell line to assess carboplatin sensitivity. Fyn expression was significantly higher in platinum-resistant patients compared with in platinum-sensitive patients (P<0.01). A weighted Fyn expression score was developed and a cutoff score of 6 was determined to predict platinum sensitivity with a specificity of 65.5% and a sensitivity of 62.9%. Patients with low Fyn expression (score ≤6) exhibited higher platinum sensitivity and longer overall survival (P<0.05). Multivariate analysis identified Fyn expression and postoperative residual tumor size as independent predictors of platinum sensitivity (P=0.033 and P=0.023, respectively). In vitro, Fyn knockdown significantly increased carboplatin sensitivity in ovarian cancer cells (P<0.05). Fyn, a member of the Src family of kinases, serves a crucial role in various cellular functions and has been implicated in chemotherapy resistance. The results demonstrated a notable association between Fyn expression and platinum sensitivity in ovarian serous carcinoma. The findings suggested that Fyn may serve as a predictive biomarker for response to platinum-based chemotherapy, offering the potential for more personalized treatment strategies. To the best of our knowledge, the present study is the first to establish an association between Fyn expression and platinum sensitivity in advanced ovarian serous carcinoma. Prospective studies with larger, multi-center cohorts and comprehensive biomarker analyses are recommended to validate and extend these results, ultimately improving therapeutic strategies and patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy. Patients and methods: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM). Results: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5–19.0), 2.4 (95% CI 1.2–3.6), and 1.1 (95% CI 1.0–1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5–25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8–16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone. Conclusion: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy. [ABSTRACT FROM AUTHOR]

The treatment of acute promyelocytic leukemia (APL) has evolved with the introduction of all-trans retinoic acid (ATRA) and subsequent arsenic trioxide (ATO), particularly in standard-risk APL with an initial white blood cell count (WBC) < 10,000/μL, where a high cure rate can now be achieved. However, for some patients with risk factors, early death or relapse remains a concern. Insights from the analysis of patients treated with ATRA and chemotherapy have identified risk factors such as WBC, surface antigens, complex karyotypes, FLT3 and other genetic mutations, p73 isoforms, variant rearrangements, and drug resistance mutations. However, in the ATRA + ATO era, the significance of these risk factors is changing. This article provides a comprehensive review of APL risk factors, taking into account the treatment approach, and explores the challenges associated with APL treatments. [ABSTRACT FROM AUTHOR]

Chemotherapy causes undesirable long-term neurological sequelae, chemotherapy-induced cognitive impairment (CICI), or chemobrain in cancer survivors. Activation of programmed cell death (PCD) has been proposed to implicate in the development and progression of chemobrain. Neuronal apoptosis has been extensively recognized in experimental models of chemobrain, but little is known about alternative forms of PCD in response to chemotherapy. Activation of acetylcholine receptors (AChRs) is emerging as a promising target in attenuating a wide variety of the neuronal death associated with neurodegeneration. Thus, this study aimed to investigate the therapeutic capacity of AChR agonists on cognitive function and molecular hallmarks of multiple PCD against chemotherapy neurotoxicity. To establish the chemobrain model, male Wistar rats were assigned to receive six doses of doxorubicin (DOX: 3 mg/kg) via intraperitoneal injection. The DOX-treated rats received either an a7nAChR agonist (PNU-282987: 3 mg/kg/day), mAChR agonists (bethanechol: 12 mg/kg/day), or the two as a combined treatment. DOX administration led to impaired cognitive function via neuroinflammation, glial activation, reduced synaptic/blood–brain barrier integrity, defective mitochondrial ROS-detoxifying capacity, and dynamic imbalance. DOX insult also mediated hyperphosphorylation of Tau and simultaneously induced various PCD, including apoptosis, necroptosis, and pyroptosis in the hippocampus. Concomitant treatment with either PNU-282987, bethanechol, or a combination of the two potently attenuated neuroinflammation, mitochondrial dyshomeostasis, and Tau hyperphosphorylation, thereby suppressing excessive apoptosis, necroptosis, and pyroptosis and improving cognitive function in DOX-treated rats. Our findings suggest that activation of AChRs using their agonists effectively protected against DOX-induced neuronal death and chemobrain. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to evaluate the cost-effectiveness of serplulimab plus chemotherapy compared chemotherapy alone as first-line strategy for patients with ES-SCLC in China. Methods: A decision-analytic model that based on the Chinese health-care system perspective was conducted to evaluate the economic benefits for the two competing first-line treatment. The clinical survival and safety data were obtained from the ASTRUM-005 trial, cost and utility values were gathered from the local charges and previously published study. Both cost and utility values were discounted at an annual rate of 5%. Sensitivity analyses and subgroup analyses were performed to examine the robustness of the model results. Results: Serplulimab plus chemotherapy could bring additional 0.25 QALYs with the marginal cost of $37,569.32, resulting in an ICER of $147,908.74 per additional QALY gained. Sensitivity analyses confirmed that model results were robust. Subgroup analyses revealed that adding serplulimab to first-line chemotherapy were unlikely to be the cost-effective option for all subgroup patients. Conclusions: Serplulimab plus chemotherapy was unlikely to be the cost-effective first-line strategy compared with chemotherapy alone for patients with ES-SCLC in China. Reduced the price of serplulimab could increase its cost-effective. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced stage presentation of RB is common in low middle-income countries (LMICs) due to lack of awareness, social taboos associated with enucleation, seeking alternative conservative treatment options, and poor accessibility to health care. Over the last few decades, there have been significant advancements in the management of extraocular RB (EORB) which have improved outcomes and helped in minimizing treatment-related toxicities. The incorporation of multimodality approaches including chemotherapy, surgery, and radiotherapy (RT) has shown promising results; however, prognosis remains poor especially in LMICs. In this article, authors have discussed the ICMR consensus guidelines on the management of EORB, including metastatic RB. [ABSTRACT FROM AUTHOR]

Induction chemotherapy (IC) recently gained importance for treatment of sinonasal undifferentiated carcinoma (SNUC). We analyzed our SNUC cases and performed a meta‐analysis with focus on survival‐rates stratified by treatment. SNUC cases at our institution were retrospectively evaluated. A systematic literature review was conducted to analyze treatment and outcome of SNUC. To calculate 5‐year and 2‐year overall survival (OS), individual patient data (IPD) were analyzed using Kaplan–Meier estimators and Cox proportional hazard regression to identify associations between types of therapy and survival. A random effects model for pooled estimates of 5‐year survival was applied to studies without IPD data. Five‐year OS of our SNUC cases (n = 9) was 44.4%. The IPD analysis (n = 192) showed a significantly better 5‐year OS for patients who received induction chemotherapy (72.6% vs. 44.5%). The pooled 5‐year OS of 13 studies identified in the literature search was 43.8%. IC should be considered in every patient diagnosed with SNUC. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumors are the most common tumors in adolescent and young men. They are curable malignancies that should be treated with curative intent, minimizing acute and long-term side effects. Inguinal orchiectomy is the main diagnostic procedure, and is also curative for most localized tumors, while patients with unfavorable risk factors for recurrence, or those who are unable or unwilling to undergo close follow-up, may require adjuvant treatment. Patients with persistent markers after orchiectomy or advanced disease at diagnosis should be staged and classified according to the IGCCCG prognostic classification. BEP is the most recommended chemotherapy, but other schedules such as EP or VIP may be used to avoid bleomycin in some patients. Efforts should be made to avoid unnecessary delays and dose reductions wherever possible. Insufficient marker decline after each cycle is associated with poor prognosis. Management of residual masses after chemotherapy differs between patients with seminoma and non-seminoma tumors. Patients at high risk of relapse, those with refractory tumors, or those who relapse after chemotherapy should be managed by multidisciplinary teams in experienced centers. Salvage treatment for these patients includes conventional-dose chemotherapy (TIP) and/or high-dose chemotherapy, although the best regimen and strategy for each subgroup of patients is not yet well established. In late recurrences, early complete surgical resection should be performed when feasible. Given the high cure rate of TGCT, oncologists should work with patients to prevent and identify potential long-term side effects of the treatment. The above recommendations also apply to extragonadal retroperitoneal and mediastinal tumors. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is a serious challenge cancer patients face today. Various factors are involved in cardiotoxicity. Circular RNAs (circRNAs) are one of the effective factors in the occurrence and prevention of cardiotoxicity. circRNAs can lead to increased proliferation, apoptosis, and regeneration of cardiomyocytes by regulating the molecular pathways, as well as increasing or decreasing gene expression; some circRNAs have a dual role in cardiomyocyte regeneration or death. Identifying each of the pathways related to these processes can be effective on managing patients and preventing cardiotoxicity. In this study, an overview of the molecular pathways involved in cardiotoxicity by circRNAs and their effects on the downstream factors have been discussed. [ABSTRACT FROM AUTHOR]

Cardiac toxicity is an adverse event of several classes of anti-cancer drugs. Herein, we present the case of a 52-year-old woman with metastatic renal cell carcinoma (RCC), previously treated with debulking surgery, pembrolizumab (immune checkpoint inhibitor) in combination with axitinib (tyrosine kinase inhibitor (TKI)), followed by lenvatinib (TKI) and belzutifan (HIF-2α inhibitor), who developed myocarditis proven by cardiac magnetic resonance and endomyocardial biopsy. The case was notable for reporting a not-yet described adverse event during treatment with belzutifan plus lenvatinib, the etiology of which was of unobvious determination given the pre-exposure to pembrolizumab, a known cause of drug-related myocarditis. We surmise that myocarditis was a delayed adverse event related to pembrolizumab (8 months after treatment interruption), although we emphasize that only attentive monitoring of cardiac adverse events of patients exposed to belzutifan and lenvatinib in the context of large clinical trials may rule out any causal implication of these drugs. [ABSTRACT FROM AUTHOR]