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Background: Prostate cancer is the second leading cause of death among American men. If detected and treated at an early stage, prostate cancer is often curable. However, an advanced stage such as metastatic castration-resistant prostate cancer (mCRPC) has a high risk of mortality. Multiple treatment options exist, the most common included docetaxel, abiraterone, and enzalutamide. Docetaxel is a cytotoxic chemotherapy, whereas abiraterone and enzalutamide are androgen receptor pathway inhibitors (ARPI). ARPIs are preferred over docetaxel due to lower toxicity. No study has used machine learning with patients' demographics, test results, and comorbidities to identify heterogeneous treatment rules that might improve the survival duration of patients with mCRPC., Objective: This study aimed to measure patient-level heterogeneity in the association of medication prescribed with overall survival duration (in the form of follow-up days) and arrive at a set of medication prescription rules using patient demographics, test results, and comorbidities., Methods: We excluded patients with mCRPC who were on docetaxel, cabaxitaxel, mitoxantrone, and sipuleucel-T either before or after the prescription of an ARPI. We included only the African American and white populations. In total, 2886 identified veterans treated for mCRPC who were prescribed either abiraterone or enzalutamide as the first line of treatment from 2014 to 2017, with follow-up until 2020, were analyzed. We used causal survival forests for analysis. The unit level of analysis was the patient. The primary outcome of this study was follow-up days indicating survival duration while on the first-line medication. After estimating the treatment effect, a prescription policy tree was constructed., Results: For 2886 veterans, enzalutamide is associated with an average of 59.94 (95% CI 35.60-84.28) more days of survival than abiraterone. The increase in overall survival duration for the 2 drugs varied across patient demographics, test results, and comorbidities. Two data-driven subgroups of patients were identified by ranking them on their augmented inverse-propensity weighted (AIPW) scores. The average AIPW scores for the 2 subgroups were 19.36 (95% CI -16.93 to 55.65) and 100.68 (95% CI 62.46-138.89). Based on visualization and t test, the AIPW score for low and high subgroups was significant (P=.003), thereby supporting heterogeneity. The analysis resulted in a set of prescription rules for the 2 ARPIs based on a few covariates available to the physicians at the time of prescription., Conclusions: This study of 2886 veterans showed evidence of heterogeneity and that survival days may be improved for certain patients with mCRPC based on the medication prescribed. Findings suggest that prescription rules based on the patient characteristics, laboratory test results, and comorbidities available to the physician at the time of prescription could improve survival by providing personalized treatment decisions., (©Deepika Gopukumar, Nirup Menon, Martin W Schoen. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 19.11.2024.)

Introduction: Consultation audio recordings improve patient decision-making but are underutilized. Patient-administered recording apps on mobile devices may increase access, but implementation has not been evaluated., Methods: We conducted a single-arm study delivering education, coaching, and reminders for patients to record their appointment using a mobile recording app. Patients had progressive, advanced prostate cancer and an upcoming appointment where the option of docetaxel would be discussed. We used the RE-AIM framework for evaluation. Reach was the proportion of patients who participated. Effectiveness was change in informed decision-making pre- vs. post-appointment. We used a questionnaire evaluating patient knowledge about docetaxel (0%-100% correct) and the decisional conflict scale-informed subscale (0 = feels extremely uninformed to 100 = extremely informed) to compare means using the paired t-test. Adoption was the proportion of providers agreeing to be recorded. Implementation was coordinator adherence to intervention delivery. We conducted semistructured interviews with patients, caregivers, and providers to assess barriers, facilitators, and suggestions for recording implementation., Results: Of 102 patients approached, 50 (49%) patients participated. Mean age was 75 years, 38 (76%) were Non-Hispanic White, and 43 (86%) had telehealth appointments. Knowledge increased from 44.7% to 49.5% (p = 0.019), particularly about palliative care (42% answering correctly to 60%, p = 0.035). Decisional conflict-informed subscale increased from 48.9 to 70.9 (p < 0.001). Forty-three patients (85%) made a recording, of whom 33 (77%) reported the recording helped treatment decision-making. All 17 providers agreed to be recorded. Coordinator adherence was high. Multi-level barriers, suggestions, and facilitators mostly related to intervention complexity and stakeholder compatibility., Conclusion: Patient-administered audio recordings had a positive effect on decision-making, particularly for palliative care awareness. For broader implementation, efforts should focus on revising institutional policies; teaching patients or caregivers to use existing recording functions on their devices; leveraging artificial intelligence for transcription and summarization; and integrating recording into telehealth technology and electronic patient portals., Trial Registration: https://clinicaltrials.gov/study/NCT05127850., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: In the global ARASENS study (NCT02799602), darolutamide plus androgen-deprivation therapy (ADT) and docetaxel significantly reduced risk of death by 32.5% versus placebo plus ADT and docetaxel (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57-0.80; p < 0.0001), with a favorable safety profile in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We investigated outcomes in Japanese participants., Methods: Patients were randomized 1:1 to oral darolutamide 600 mg twice daily or placebo, plus ADT and docetaxel. The primary endpoint was overall survival., Results: The Japanese subgroup comprised 148 patients (darolutamide 63, placebo 85). In the Japanese versus overall population, more patients were aged ≥75 years (darolutamide/placebo 35%/22% vs. 16%/17%) and had body mass index <25 kg/m 2 (78%/79% vs. 46%/43%), The ECOG performance status 0 (92%/88% vs. 72%/71%), de novo mHSPC (95%/97% vs. 86%/87%), and Gleason score ≥8 (94%/92% vs. 78%/79%). Median treatment duration was 43.3/15.4 months for darolutamide/placebo. The overall survival HR for darolutamide versus placebo was 0.91 (95% CI 0.50-1.64), despite 85% of patients in the placebo group receiving subsequent life-prolonging therapy. Darolutamide prolonged time to castration-resistant prostate cancer (HR 0.31; 95% CI 0.17-0.55). Treatment-emergent adverse event incidences were generally similar between groups. Adverse events known to be associated with docetaxel (e.g., neutropenia) were more frequent in the Japanese versus overall population., Conclusion: In conclusion, efficacy outcomes showed positive trends for darolutamide plus ADT and docetaxel in Japanese patients with mHSPC, consistent with the overall population, despite higher risk factors. The combination was well tolerated, with no new safety signals in Japanese patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC)., Methods: We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency., Results: Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates., Conclusions: Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The LUNAR trial demonstrated the significant efficacy and safety of Tumor Treating Fields (TTFields) plus standard-of-care (SOC) [immune checkpoint inhibitor (ICI) and docetaxel (DTX)] for patients with previously treated metastatic non-small cell lung cancer (mNSCLC). However, it remains uncertain as to whether the high costs are justified by the corresponding survival benefits. Here, the cost-effectiveness of using TTFields plus SOC for treating mNSCLC was evaluated from the perspective of the Chinese healthcare system., Methods: A Markov model with a 15-year time horizon was established and used to comparedeveloped to enable the simulation of treatment-associated costs and patient outcomes when comparing TTFields plus SOC to SOC alone. Primary outcomes for these analyses included total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) values. The impact of paramere uncertainty on model outcomes was evaluated through sensitivity analyses. Additional subgroup and scenario analyses were also performed to extend these results., Results: While TTFields plus SOC exhibited a $74,688 increase in total costs relative to SOC ($96,092 vs. $21,404), it was associated with 0.38 additional QALYs (1.08 vs. 0.82 QALYs) for an ICER of $284,490/QALY. This value exceeded the $35,983/QALY willingness-to-pay (WTP) threshold selected for these analyses by a wide margin. Relative to ICI and DTX treatment, the incremental costs of TTFields plus ICI and TTFields plus DTX were $78,115 and $71,307, respectively, with corresponding gains of 0.42 and 0.13 QALYs, yielding ICERs of $187,434/QALY, and $546,386/QALY. The parameter that most strongly impacted the results of these analyses was the cost of TTFields., Conclusion: The results indicated that given current treatment costs, TTFields plus SOC was insufficiently cost-effective in treating patients with mNSCLC in China, although TTFields plus ICI yields substantial health benefits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pei, Xiao and Yang.)

Background: Docetaxel (DOC) and ramucirumab (RAM) is one of the most effective regimens for advanced non-small cell lung cancer (NSCLC) treatment. In our previous study, baseline anemia was identified as a preventive factor against the development of severe adverse effects during the first treatment cycle. It was hypothesized that anemia directly promotes tumor angiogenesis, leading to the elevation of RAM efficacy with increased DOC delivery to tumors, while reducing DOC delivery to other organs, potentially mitigating severe adverse effects. If this hypothesis is correct, patients with baseline anemia may have better clinical outcomes than those with normal hemoglobin levels. In this study, we aimed to investigate the effect of baseline anemia on the efficacy of DOC + RAM in treating advanced NSCLC in a real-word setting., Methods: Patients with advanced NSCLC receiving DOC + RAM (n = 72) were retrospectively assessed. They were categorized into a control group with normal baseline hemoglobin levels and an anemia group with baseline anemia. The primary endpoint was progression-free survival (PFS) evaluation., Results: Patients in the anemia group had a significantly shorter PFS than that of patients in the control group (median PFS: 3.2 and 6.2 months; 95% confidence interval [CI]: 2.2-4.8 and 4.3-9.9 months, respectively;P = 0.008). In addition, the disease control rate in the anemia group was 65.8%, which was significantly lower than that in the control group (93.6%; P = 0.007). Overall survival tended to be shorter in patients with anemia than in controls, although the difference was not statistically significant (P = 0.07). Multivariate Cox hazard analysis suggested that baseline anemia was a singular risk factor for poor PFS (adjusted hazard ratio 1.84, 95% CI 1.08-3.13; P = 0.02). The incidence of severe adverse effects did not differ between the two groups., Conclusions: This study suggests that the PFS of patients with anemia treated with DOC + RAM for advanced NSCLC is shorter than that of those without the symptoms., (© 2024. The Author(s).)

Rationale: The incidence of pregnancy-associated breast cancer (PABC) is relatively low, but it has been increasing in recent years. The onset of PABC causes serious harm to the fetus and the mother due to the unique physiological characteristics of pregnancy, which poses a particular challenge to clinicians. This article reports a case of pregnancy-associated triple-negative breast cancer and describes the patient characteristics and systematic treatment of this type of breast cancer., Patient Concerns: A 33-year-old woman was admitted to hospital with a left breast mass that had appeared more than a year earlier. She was a second-time pregnant woman with a single live intrauterine fetus at 23 + 4 weeks of gestation. During the examination of the left breast, a 6 by 8 cm sized mass can be observed on the upper outer quadrant., Diagnosis: Pregnancy-associated triple-negative breast cancer., Intervention: The patient underwent a breast ultrasound which showed a left breast mass and the diagnosis was confirmed by a puncture biopsy of the left breast mass. The pregnancy was terminated after multidisciplinary discussion, taking into account the wishes of the patient and her family. After termination of the pregnancy, all treatments were given according to the standard triple-negative breast cancer (TNBC) treatment protocol. The patient was treated with neoadjuvant chemotherapy with epirubicin in combination with docetaxel (TE) in cycles of 21 days. After 3 cycles of TE, a modified radical mastectomy for left breast cancer was performed, and the appropriate radiotherapy and chemotherapy treatments were carried out in sequence., Outcomes: After the surgery, the disease-free survival for the patient was 3 months until local metastases were diagnosed. Thus the radiotherapy and chemotherapy were carried out, and then the patient was in good general condition with no recurrence or metastases., Lessons: Clinicians need more research into the diagnosis, treatment and prognosis of PABC. Improving the rate of early diagnosis and using standardized and individualized comprehensive treatment plans will minimize fetal damage and improve survival and quality of life for patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Anlotinib, an oral multitarget tyrosine kinase inhibitor, has shown the ability to inhibit tumor angiogenesis. This study aimed to assess the effectiveness and safety of anlotinib plus docetaxel, epirubicin, and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen for locally advanced TNBC., Methods: Locally advanced TNBC patients who had received no prior systemic treatment were eligible for this study. The enrolled patients were scheduled to undergo six cycles of anlotinib (12 mg, d1-14, q3w) plus docetaxel (75 mg/m2, d1, q3w), epirubicin (75 mg/m2, d1, q3w) and cyclophosphamide (600 mg/m2, d1, q3w) prior to surgery, unless there was disease progression or severe toxicity. The primary objective of this study was the safety of this therapeutic regimen, and the secondary objective was the tumor response. The safety of this regimen was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the efficacy of this treatment was measured using the Response Evaluation Criteria in Solid Tumors version 1.1., Results: A total of 18 patients were included in this study. Participants completed an average of 5.56 neoadjuvant treatment cycles. The objective response rate (ORR) was 83.33%, and the disease control rate was 100%, respectively. The pCR was 55.6%. No patients discontinued therapy because of Adverse effects (AEs). Grade 3 or 4 AEs were observed in 5 cases (27.8%), with neutropenia and palmar-plantar erythrodysesthesia syndrome being the most common., Conclusions: Anlotinib combined with TEC as neoadjuvant therapy demonstrated manageable toxicity and promising antitumor activity for locally advanced TNBC. Further investigation of this combination regimen is warranted., (© 2024. The Author(s).)

Docetaxel is commonly used for treatment of castration-resistant prostate cancer. Unfortunately, many prostate cancer patients develop resistance to docetaxel. Clinical markers less invasive than biopsies, such as blood samples, would be ideal for monitoring and predicting patient treatment outcomes to docetaxel. Lipid alterations are often associated with the progression of many cancers, including prostate cancer. This study investigated the use of lipids from whole blood as clinical markers for docetaxel resistance in a small cohort of patients with prostate cancer. Qualitative lipidomics was performed by liquid chromatography-tandem mass spectrometry to assess the lipid composition of prostate cancer cells exposed to docetaxel as well as whole blood from prostate cancer patients before, during and after docetaxel treatment. Three patients had castration resistant prostate cancer, three had castration sensitive prostate cancer, and four had de novo prostate cancer during the extent of the study. Mean decrease accuracy and classical univariate receiving operating characteristic curve analyses were performed to identify potential biomarkers. In total, 245 and 221 altered lipids were identified from a second stage of mass spectrometry analysis of prostate cancer cells and clinical blood samples, respectively. Both models indicated that docetaxel treatment altered ether-linked phosphatidylcholines, lysophosphatidylcholine, diacylglycerols, ceramides, hexosylceramides, and sphingomyelins. The results also indicated several lipid changes were associated with sphingolipid signaling and metabolism, and glycerophospholipid metabolism. Collectively, these data suggest the potential usage of identified lipid species as indicators of docetaxel resistance in prostate cancer., (© 2024. The Author(s).)

Docetaxel is a commonly used taxane chemotherapeutic agent in the treatment of a variety of cancers, including breast cancer, ovarian cancer, prostate cancer, non-small cell lung cancer, gastric cancer, and head and neck cancer. Docetaxel exerts its anti-cancer effects through inhibition of the cell cycle and induction of proapoptotic activity. However, docetaxel also impacts rapidly proliferating normal cells in the scalp hair follicles (HFs), rendering the HFs vulnerable to docetaxel-induced cell death and leading to chemotherapy-induced alopecia (CIA). In severe cases, docetaxel causes persistent or permanent CIA (pCIA) when hair does not grow back completely six months after chemotherapy cessation. Hair loss has severe negative impacts on patients' quality of life and may even compromise their compliance with treatment. This review discusses the notable prevalence of docetaxel-induced CIA and pCIA, as well as their prevention and management. At this moment, scalp cooling is the standard of care to prevent CIA. Treatment options to promote hair regrowth include but are not limited to minoxidil, photobiomodulation (PBMT), and platelet-rich plasma (PRP). In addition, a handful of current clinical trials are exploring additional agents to treat or prevent CIA. Research models of CIA, particularly ex vivo human scalp HF organ culture and in vivo mouse models with human scalp xenografts, will help expedite the translation of bench findings of CIA prevention and/or amelioration to the clinic.

Background: No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget's disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD., Methods: In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period., Results: All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated., Conclusion: The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073)., (© The Author(s) 2024. Published by Oxford University Press.)

Aim: to analyze the short- and long-term outcomes of surgical treatment of patients with gastric cancer who received perioperative chemotherapy (PCT) FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel)., Materials and Methods: A retrospective cohort study included 146 patients who received surgical treatment at the Faculty Surgery Clinic of Sechenov University for gastric cancer (GC) and/or EGJC Sievert Type II-III in the period from January 2018 to December 2022. The main group consisted of 28 patients who received PCT FLOT; there were 118 patients operated "up front" in control group. Patients in both groups did not statistically differ in average age (p=0.110), ASA (p=0.541) and ECOG (p=0.12) status, localization (p=0.063), depth of invasion (p=0.099) and histological structure of tumor (p=0.787)., Results: In 92.9% of the patients in the main group and in 94.9% of the control group, R0 resection margins (p=0.750) were achieved. The number of dissected lymph nodes was statistically significantly higher in the main group (average 26 vs 21; p=0.010). There was no difference in intraoperative blood loss (p=0.294) and time of hospital stay (p=0.992); the average duration of surgery in the main group was 319 minutes, compared to 250 minutes in the control group (p<0.001). In the early postoperative period, the total number of complications (CD Ⅰ-IV) was higher in the main group (p=0.031), however, there was no difference in the number of minor (CD Ⅰ-Ⅱ; p=0.094) and significant (CD III-V; p=0.142) complications. Postoperative mortality in the first 30 days after the surgical treatment was 3.6% and 2.5% in the main and control groups, respectively (p=0.764). The overall 6-month survival rate in the control group was 95.9% vs 90.9% in the main group, and the 12-month survival rate was 88.8% vs 75.7%, respectively. The reccurence-free 6-month survival rate in the control group was 96%, in the main group - 100%; the reccurence-free 12-month survival rate in the control group was 92.1%, in the PCT group - 93.3%., Conclusion: PCT FLOT in the treatment of GC does not increase the level of intraoperative blood loss, the number of postoperative complications and the duration of hospital stay. The 6-month and one-year survival rates did not differ in the two groups. Considering that the majority of patients in the PCT group belonged to the cN+ category, with an initially less favorable treatment prognosis, it can be assumed that comparable survival results were achieved thanks to PCT.

Introduction: Osteosarcoma is the most common primary malignancy of the bone. There is a lack of effective treatments for patients who experience relapsed osteosarcoma. One treatment for relapsed patients is gemcitabine and docetaxel combination chemotherapy (GEMDOX). This systematic review aimed to establish the efficacy of this chemotherapy regimen, as well as identify the common severe toxicities that are associated with it. Resistant osteosarcoma cell lines developed from MG-63 and HOS-143B were used to represent relapsed osteosarcoma patients in a pre-clinical study., Results: We identified 11 retrospective and Phase II studies that were suitable for inclusion in our review. 10.65% of patients had a response to gemcitabine and docetaxel combination therapy and the disease control rate was 35% (n = 197). 36%, 35.3% and 18.04% of patients experienced grade 3 or 4 neutropenia, thrombocytopenia and anaemia respectively (n = 133). Male patients (X 2  = 9.14, p < 0.05) and those below the age of 18 (X 2  = 10.94, p < 0.05) responded better to GEMDOX treatment than females and patients older than 18 years. The resistant osteosarcoma cell lines remained sensitive to either single-agent gemcitabine, docetaxel, and the combination of both. Cisplatin-resistant models (MG-63/CISR8 & HOS-143B/CISR8) were the most responsive to GEMDOX treatment compared to doxorubicin, methotrexate, and triple-combination resistant models., Conclusion: GEMDOX treatment has potential efficacy in relapsed osteosarcoma patients especially those with cisplatin resistance. To directly compare the efficacy of GEMDOX therapy against other therapies randomised phase III clinical trials with adequate patient follow up must be performed to improve treatment options for osteosarcoma., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: The high costs of cancer care can cause significant harm to patients and society. Prostate cancer, the leading nonskin malignancy in men, is responsible for the second-highest out-of-pocket (OOP) payments among all malignancies. Multiple first-line treatment options exist for metastatic castration-resistant prostate cancer (mCRPC); although their costs vary substantially, comparative effectiveness data are limited. There is little evidence of how gross payments made by insurers and OOP payments made by patients differ by treatment and health plan type and how these payment differences relate to utilization., Study Design: Retrospective cohort study., Methods: We used IBM MarketScan databases from 2013-2019 to identify men with prostate cancer who initiated treatment with 1 of 6 drugs approved for first-line treatment of mCRPC. We calculated and compared gross and OOP payments and drug utilization across drug and insurance plan types., Results: We identified 4298 patients who met our inclusion criteria. Insurer payments varied substantially by first-line therapy but were similar across different health plan types, except for docetaxel. OOP payments for a given first-line therapy, in contrast, varied by health plan type. Utilization of first-line therapies varied by plan type in unadjusted analyses, but not after adjusting for patient characteristics., Conclusions: The extent to which patient OOP payments for drugs reflect differences in gross payments made by insurers varies across health insurance plan types. However, even though OOP payments for the same treatment differ across plan types, treatment choice is not significantly different across type of health insurance after controlling for patient characteristics.

Primary ovarian sarcoma is a rare malignancy, with primary ovarian leiomyosarcoma being even rarer because of the lack of smooth muscle in the ovaries. We herein report a case of primary ovarian leiomyosarcoma in a woman in her late 50s who presented with a 6-month history of abdominal pain. Imaging revealed a pelvic mass. The patient underwent surgery and was diagnosed with ovarian leiomyosarcoma. One month postoperatively, she began gemcitabine and docetaxel chemotherapy and continued this treatment for 6 months. Eight months postoperatively, however, recurrence was detected in the pelvic cavity. This case is reported with the aim of raising awareness about this rare disease., Competing Interests: Declaration of conflicting interestThe authors declare that they have no conflict of interest regarding the publication of this research.

Background: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer., Materials and Methods: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab)., Results: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups., Conclusion: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: ARASENS was a randomized, double-blind, phase 3 trial comparing darolutamide + docetaxel + androgen deprivation therapy (ADT) with placebo + docetaxel + ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Objective: To use clinical trial data from ARASENS to understand whether the addition of darolutamide to docetaxel + ADT leads to increased hospitalizations and to estimate the budget impact on the US health care system., Methods: We used mixed-effects negative binomial regression to estimate hospitalization and intensive care unit (ICU) admission rates and length of hospital stay (LoHS) counts. Hospitalization rates were estimated per treatment arm for the period during and after administration of docetaxel. Based on these estimates, a budget impact analysis evaluated the hospitalization costs (including ICU admissions) and standalone ICU hospitalization costs for the totality of the US population over a 5-year time horizon. The analysis compared a scenario without darolutamide vs one with darolutamide included in the US payer formulary. Hospitalization estimates were varied in a one-way sensitivity analysis., Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalizations across both arms. The addition of darolutamide was associated with a numerical reduction in the rate of hospitalization (per year) due to any reason both during docetaxel treatment (1.01 visits per year [95% CI = 0.82-1.20] vs 1.18 visits per year [95% CI = 0.96-1.41]) and after docetaxel treatment (0.28 visits per year [95% CI = 0.23-0.34] vs 0.33 visits per year [95% CI = 0.27-0.40]). Darolutamide was associated with a marginally longer LoHS per hospitalization compared with placebo (+1.90 days per year) both during and after docetaxel treatment. ICU admissions were low in the ARASENS data; admission rates were assumed to be the same during and after docetaxel treatment. ICU admission rate estimates were equivalent across arms (0.02 visits per year [95% CI = 0.01-0.03]). The budget impact per treated member per month represents a cost-neutral option after Year 5 with a cumulative budget impact of -$9.71., Conclusions: The addition of darolutamide to docetaxel + ADT was associated with a numerically lower rate of hospitalization but marginally longer LoHS compared with docetaxel + ADT alone. Darolutamide represents a cost-neutral alternative per treated member per month compared with docetaxel + ADT with regard to hospitalizations at the end of a 5-year time horizon.

Background/aim: In patients with metastatic castration-sensitive prostate cancer (mCSPC), upfront treatment intensification with the addition of new hormonal agents and/or docetaxel to androgen deprivation therapy (ADT) is recommended. However, this modality is potentially excessive in a subset of these patients. This study aimed to identify patients who may be eligible to omit upfront treatment intensification., Patients and Methods: Patients with mCSPC who underwent ADT were enrolled. The association between undetectable prostate-specific antigen (PSA) (<0.2 ng/ml) after ADT initiation and overall or castration-resistance-free survival was evaluated., Results: Ninety-seven out of the 242 enrolled patients had low-risk and/or low-volume cancer and were further analyzed. Of these, 45 (46.4%) patients achieved undetectable PSA. The median follow-up period after ADT initiation was 70 months. The median overall survival among patients with undetectable PSA was quite long, reaching 226 months and significantly longer than that among patients with detectable PSA [71 months, hazard ratio (HR)=0.27, 95% confidence interval (CI)=0.15-0.49, p<0.001]. Time to development of castration-resistance was also long and significantly longer in the undetectable PSA group than that in the detectable PSA group (median: 124 vs. 17 months, HR=0.20, 95% CI=0.12-0.34, p<0.001)., Conclusion: Patients with low-risk and/or low-volume mCSPC showed long-term survival when undetectable PSA was achieved during conventional ADT. In these patients, skipping upfront treatment intensification does not seem to negatively impact survival., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT., Methods: In this retrospective single center study, all patients with RAAS of the breast treated between 1994 and 2024 are included. Since 2018, NACT is considered a treatment option for this patient population in our institute. The difference in oncological outcomes of patients with and without NACT were compared., Results: Thirty-five women were included. Thirteen (37 %) received NACT of which five (39 %) also had neoadjuvant re-irradiation with hyperthermia. Eleven patients (85 %) received paclitaxel, the other two (15 %) had doxorubicine/docetaxel. Complete pathological response was found in 69 % (n = 9). Median follow up was 41 months (range 24-56) for patients with NACT and 44 (range 20-108) for patients without NACT. In the NACT group, only one patient developed a recurrence after 6.5 years. Patients with NACT had improved oncological outcomes compared to patients without NACT in terms of 3-year local recurrence free survival (100% vs. 63.9 %, p = 0.14), distant metastasis free survival (100 % vs. 47.5 %, p = 0.005), and overall survival (100% vs. 56.1 %, p = 0.016)., Conclusion: In this study, neoadjuvant taxanes for RAAS of the breast leads to improved distant metastasis free survival and overal survival in patients treated with NACT compared to no NACT., Competing Interests: Declaration of competing interest N. Steeghs provided consultation or attended advisory boards for Boehringer Ingelheim, Ellipses Pharma, GlaxoSmithKline, Incyte, Luszana. N Steeghs received research grants from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Lixte, Luszana, Merck, Merck Sharp & DohmeMerck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho, Takeda. All outside the submitted work, all payment to the Netherlands Cancer Institute. W. van der Graaf: Advisory boards SpringworkTx, Agenus and PTC Therapeutics (all to the institute) and research grants from Eli Lilly (to the Institute). W. van Houdt: advisory boards of Amgen, Boehringer Ingelheim, Sanofi, Novartis, Sirius Pintuition, Belpharma. All payment to the Netherlands Cancer Institute., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The management of advanced prostate cancer continues to evolve rapidly, particularly with the earlier use of survival-prolonging therapies in metastatic castration-sensitive prostate cancer (mCSPC). Though approved prior to the use of intensification therapy in mCSPC, taxane-based chemotherapies remain a relevant option for patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is little evidence determining the outcomes of taxane chemotherapies as the first subsequent taxane (FST) in mCRPC pts who received docetaxel intensification (DI) in mCSPC. The purpose of this study is to compare outcomes between the survival-prolonging taxanes, docetaxel and cabazitaxel as FST after DI., Methods: New patient consults seen at the Cross Cancer Institute from 1 July 2014 to 31 December 2020 were retrospectively reviewed. Pts were considered eligible if they received DI for mCSPC and then received either docetaxel or cabazitaxel in mCRPC. Variables of interest were collected from electronic medical records. The primary endpoint was ≥50% PSA response at 12 weeks relative to baseline for FST. Secondary endpoints included OS from mCSPC diagnosis, as well as PFS and OS from the FST start date. PSA responses were compared using the chi-squared test, and time-based endpoints were compared using the Kaplan-Meier method., Results: In total, 34 pts were identified: docetaxel = 22 and cabazitaxel = 12 as FST. 91.2% of pts (docetaxel 95.5% vs. cabazitaxel 83.3%) received FST in 2nd line mCRPC. The median age at diagnosis (63.1 vs. 67.1 yrs, p = 0.236) and the median time to CRPC (18.6 vs. 14.2 mos, p = 0.079) were similar for docetaxel and cabazitaxel, respectively. The median time to FST (24.1 vs. 34.6 mos, p = 0.036) and OS from mCSPC diagnosis (30.9 vs. 52.7 mos, p = 0.002) were significantly shorter for pts receiving cabazitaxel vs. docetaxel. PSA responses occurred in 40.9% of pts treated with docetaxel compared to 25.0% treated with cabazitaxel ( p = 0.645). There was no significant difference in median PFS (2.7 vs. 3.5 mos, p = 0.727) or median OS (11.4 vs. 8.1 mos, p = 0.132) from the time of FST for pts treated with docetaxel vs. cabazitaxel, respectively., Conclusions: Both docetaxel and cabazitaxel demonstrated activity as FST after DI in mCSPC. Pts who received cabazitaxel had a shorter time to FST and OS from mCSPC. The reasons for this may reflect clinician preference for cabazitaxel in pts with aggressive or rapidly progressing disease. No difference was found in PSA response, PFS, or OS from FST with docetaxel compared to cabazitaxel. While limited by its retrospective nature and small sample size, this study suggests that docetaxel is active as FST despite treatment with DI in mCSPC.

Background: Anthracycline-taxane is the standard chemotherapy strategy for treating high-risk early breast cancer despite the potentially life-threatening adverse events caused by anthracyclines. Commonly, the combination of docetaxel and cyclophosphamide (TC) is considered an alternative option. However, the efficacy of TC compared to anthracycline-taxane chemotherapy is unclear. This study compares disease-free survival (DFS), overall survival (OS) and cardiotoxicity between adjuvant TC and anthracycline-taxane for stages I-III, HER2-negative breast cancer., Methods: A systematic search on MEDLINE, Embase and Cochrane CENTRAL for randomized-controlled trials published until 11 March 2024, yielded 203 studies with 11,803 patients, and seven trials were included., Results: TC results in little to no difference in DFS (HR 1.09, 95% CI 0.98-1.20; moderate-certainty of evidence); OS (1.02, 95% CI 0.89-1.16; high-certainty of evidence); and cardiotoxicity (RR 0.54, 95% CI 0.16-1.76; high-certainty of evidence), compared to anthracycline-taxane. In the subgroup analysis, patients with ≥4 lymph nodes had improved DFS from anthracycline-taxane over TC., Conclusions: Overall, there was no difference between TC and anthracycline-taxane in DFS, OS and cardiotoxicity. In women with ≥4 nodes, anthracycline-taxane was associated with a substantial reduction in relapse events, compared to TC. Our study supports the current standard of practice, which is to use anthracycline-taxane and TC chemotherapy as a reasonable option in select cases.

Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival., Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy., Design, Setting, and Participants: This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022., Intervention: Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration., Main Outcomes and Measures: The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression., Results: Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups., Trial Registration: ClinicalTrials.gov Identifier: NCT00593697.

High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate instrument. Correlative analyses included pharmacokinetics and oxidative stress markers. Eighty-nine percent of patients previously had three or more lines of therapy. The PSA50 response rate was 41% in the HDIVC group and 33% in the placebo group (P = 0.44), with comparable adverse event rates in both groups. There were no significant differences in Functional Assessment of Cancer Therapy-Prostate scores. The median radiographic progression-free survival was not significantly different between the HDIVC and placebo groups, with durations of 10.1 and 10.0 months (HR, 1.35; 95% confidence interval, 0.66-2.75; P = 0.40), respectively. The median overall survival was 15.2 months in the HDIVC group and 29.5 months in the placebo group (HR, 1.98; 95% confidence interval, 0.85-4.58; P = 0.11). HDIVC did not decrease F2-isoprostanes, indicators of oxidative stress. The study was suspended after prespecified interim analysis indicated futility in achieving primary endpoints. In this patient population, combining HDIVC with docetaxel did not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. Findings do not support the routine use of HDIVC in mCRPC treatment outside of clinical trials., Significance: This is the first randomized, placebo-controlled, double-blind trial to evaluate HDIVC in cancer treatment. The addition of HDIVC to docetaxel in patients with mCRPC does not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. The routine use of HDIVC in mCRPC treatment is not supported outside of clinical trials., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT)., Methods: In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III-IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy., Results: After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT., Conclusions: This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting., Trial Registration: www., Clinicaltrials: gov . NCT02923258 (date of registration: October 4, 2016)., (© 2024. The Author(s).)

Background: Tislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective., Methods: A dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results., Results: The tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained., Conclusion: The administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Fan, Zhang, Jiang, Wu, Yang, Li and Liu.)

Sinonasal squamous cell carcinoma (SNSCC) is the most common, high-aggressive sinonasal malignancies that have remained relatively stable poor outcomes over the past decade. As a first-line treatment for SNSCC, surgery plus adjuvant radiotherapy is recommended. However, complete surgical resection may not be appropriate due to the proximity of the nasal cavity and sinuses to key structures such as orbit or intracranial. Currently, immune checkpoint inhibitors (ICIs) have been established as one of the first-line therapies for many solid tumors with unresectable stage. However, evidence on the efficacy of ICIs in sinonasal malignancy is scarce and no ICIs are approved for use in SNSCC up to day. In this report, we report a case of a 64-year-old man with SNSCC treated by multi-protocol exploration. The patient achieved pathological complete response (pCR) after receiving two cycles of Docetaxel and cisplatin combined with tislelizumab. To the best of our knowledge, this is the first case of SNSCC treated with tislelizumab that achieved pCR. This case offers real-world evidence that chemotherapy plus immunotherapy is a promising treatment for SNSCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang, Li, Liang and Zhang.)

The present study investigated the relationship between MSH3 and MSH6 genes in lung cancer patients. Genotyping of lung cancer patients and healthy controls was performed. Odds ratio values were calculated and survival analysis performed. Patients with mutant genotype (TT) for MSH6 polymorphism have 1.5-fold risk for the development of lung cancer (p = 0.03). For non-smokers, the mutant-type genotype had a threefold increased risk of lung cancer (p = 0.01). Patients administered with docetaxel and carbo/cisplatin and carrying GT genotype for MSH6 polymorphism, patients reported a decrease in median survival time (4.9 vs 9.13 months). MSH3 and MSH6 polymorphisms are involved in modulating the risk towards lung cancer. MSH6 polymorphism is associated with high mortality rate for patients undergoing cisplatin and docetaxel chemotherapy., (© 2024. The Author(s).)

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P =0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P =0.013) and 2-year LPR (66.6% vs 48.6%, P =0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P <0.001) and 2-year survival rate (76.9% vs 45.5%, P =0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P <0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug - daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57-0.80; p < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool., (© 2024. Crown.)

This study compared different doublet and triplet therapies for efficacy and safety in metastatic hormone-sensitive prostate cancer (mHSPC). PubMed, EMBASE, and the Cochrane Library were comprehensively searched for eligible randomized controlled trials (RCTs) published from inception to October 2023. Interventions included abiraterone, apalutamide, enzalutamide, docetaxel, darolutamide, and androgen deprivation therapy (ADT), either as doublet or triplet therapies. The outcomes examined were overall survival (OS), progression-free survival (PFS), castration-resistant prostate cancer (CRPC)-free survival, time to symptomatic skeletal event (SSE), and toxicity. The surface under the cumulative ranking curve (SUCRA) was determined to identify the preferred treatments. Ten RCTs were included. The combination of darolutamide, docetaxel, and ADT had the highest SUCRA of 84.3 for OS, followed by combined abiraterone, docetaxel, and ADT (SUCRA = 71.6). The highest SUCRAs for PFS were observed for triplet therapies (abiraterone, docetaxel, and ADT [SUCRA = 74.9], followed by enzalutamide, docetaxel, and ADT [SUCRA = 74.3]) and other androgen receptor axis-targeted therapy-based doublet therapies (SUCRAs: 26.5-59.3). Darolutamide, docetaxel, and ADT had the highest SUCRAs, i.e ., 80.8 and 84.0 regarding CRPC-free survival and time to SSE, respectively. Regarding Grade >3 adverse events (AEs), the SUCRAs of triplet therapies (SUCRAs: 14.8-31.5) were similar to that of docetaxel and ADT (SUCRA = 39.5). Three studies had a low risk of bias in all categories; the remaining studies had at least an unclear risk of bias in at least one category. Triplet therapy demonstrated potentially enhanced effectiveness than doublet therapy in mHSPC, with acceptable safety concerns. Darolutamide might be the optimal option for triplet therapy in combination with docetaxel and ADT., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Chemoresistance is a main reason for treatment failure in patients with nasopharyngeal carcinoma, but the exact regulatory mechanism underlying chemoresistance in nasopharyngeal carcinoma remains to be elucidated. Here, we identify PJA1 as a key E3 ubiquitin ligase involved in nasopharyngeal carcinoma chemoresistance that is highly expressed in nasopharyngeal carcinoma patients with nonresponse to docetaxel-cisplatin-5-fluorouracil induction chemotherapy. We find that PJA1 facilitates docetaxel resistance by inhibiting GSDME-mediated pyroptosis in nasopharyngeal carcinoma cells. Mechanistically, PJA1 promotes the degradation of the mitochondrial protein PGAM5 by increasing its K48-linked ubiquitination at K88, which further facilitates DRP1 phosphorylation at S637 and reduced mitochondrial reactive oxygen species production, resulting in suppression of GSDME-mediated pyroptosis and the antitumour immune response. PGAM5 knockdown fully restores the docetaxel sensitization effect of PJA1 knockdown. Moreover, pharmacological targeting of PJA1 with the small molecule inhibitor RTA402 enhances the docetaxel sensitivity of nasopharyngeal carcinoma in vitro and in vivo. Clinically, high PJA1 expression indicates inferior survival and poor clinical efficacy of TPF IC in nasopharyngeal carcinoma patients. Our study emphasizes the essential role of E3 ligases in regulating chemoresistance and provides therapeutic strategies for nasopharyngeal carcinoma based on targeting the ubiquitin-proteasome system., (© 2024. The Author(s).)

Pulmonary blastoma (PB) is a rare, highly malignant tumor prone to distant metastasis and recurrence, and the prognosis of these patients is often poor. We report a case of metastatic PB with a good prognosis with the aim of providing data to support a clinical diagnosis and treatment. In December 2015, a 43-year-old male patient was admitted to our hospital because of a cough and blood-stained sputum. Positron emission-computed tomography showed massive high-density imaging in the lower lobe of the right lung, with a maximum cross-section of 76 × 58 mm. Thoracoscopic-assisted right lower lobectomy with lymph node dissection was performed. After 1 month, computed tomography showed a high possibility of metastasis. The patient then received docetaxel and cisplatin chemotherapy for a total of six courses. After chemotherapy, enhanced computed tomography showed considerable absorption of pleural effusion, and a left lobe pulmonary nodule was not detected. The postoperative pathological diagnosis was PB, and epithelial and mesenchymal differentiation components were observed. The patient continued to visit the hospital regularly for re-examination and imaging examinations. Currently, no signs of recurrence or distant metastasis have been detected., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration-resistant diagnosis. Optimal first-line therapy for those with different prognoses is unknown., Methods: We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first-line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow-up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan-Meier methods to examine prostate specific antigen (PSA) progression-free and overall survival (OS) according to prognostic group and first-line therapy, and multivariable cox regression to determine variables associated with survival outcomes., Results: Among 4135 patients, median PSA progression-free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6-7.3), and median OS 18.8 months (95% CI 18.0-19.6), ranging from 5.7 months (95% CI 4.8-7.0) in the poor prognosis group to 31.3 months (95% CI 29.7-32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2-3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34-2.31; intermediate HR 1.78, 95% CI 1.41-2.25; poor HR 8.01, 95% CI 2.93-21.9)., Conclusion: Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First-line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel's therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects., (© 2024. The Author(s).)

Background and Purpose: Perioperative 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT) is recommended in resectable esophagogastric adenocarcinoma based on randomised trials. However, the effectiveness of FLOT in routine clinical practice remains unknown as randomised trials are subject to selection bias limiting their generalisability. The aim of this study was to evaluate the implementation of FLOT in real-world patients., Methods: Retrospectively collected data were analysed in consecutive patients treated before or after the implementation of FLOT. The primary endpoint was complete pathological response (pCR) and secondary endpoints were margin-free resection (R0), overall survival (OS), relapse-free survival (RFS) tolerability of chemotherapy and surgical complications., Results: Mean follow-up time for patients treated with FLOT (n = 205) was 37.7 versus 47.0 months for epirubicin, cis- or oxaliplatin, and capecitabine (ECX/EOX, n = 186). Surgical resection was performed in 88.0% versus 92.0%; pCR were observed in 3.8% versus 2.4%; and R0 resections were achieved in 78.0% versus 86.0% (p = 0.03) in the ECX/EOX and FLOT cohorts, respectively. Survival analysis indicated no significant difference in RFS (p = 0.17) or OS (p = 0.37) between the cohorts with a trend towards increased OS in performance status 0 (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.50-1.04). More patients treated with ECX/EOX completed chemotherapy (39% vs. 28%, p = 0.02). Febrile neutropenia was more common in the FLOT cohort (3.8% vs. 11%, p = 0.0086). 90-days mortality (1.2% vs. 0%) and frequency of anastomotic leakage (8% vs. 6%) were equal and low., Interpretation: Patients receiving FLOT did not demonstrate improved pCR, RFS or OS. However, R0 rate was improved and patients in good PS trended towards improved OS.

While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics., (© 2024. The Author(s).)

Background: A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes., Patients and Methods: This multicenter, prospective study investigated the efficacy and safety of RAM plus DOC after combined chemoimmunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. An exploratory analysis measured serum cytokine levels at the start of treatment., Results: Overall, 44 patients were enrolled from 10 Japanese institutions between April 2020 and June 2022. The median PFS and OS were 6.3 and 22.6 months, respectively. Furthermore, the ORR and DCR were 36.4% and 72.7%, respectively. The high vascular endothelial growth factor D (VEGF-D) group had a significantly shorter PFS and OS. A combination of high VEGF-A and low VEGF-D levels was associated with a longer PFS., Conclusion: Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with advanced NSCLC in a real-world setting., (© The Author(s) 2024. Published by Oxford University Press.)

Background: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients., Methods: Patients with cT3-4 N any M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR)., Results: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX., Conclusions: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation., (© 2024. The Author(s).)

The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes., (© 2024. The Author(s).)

Background: Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC., Methods: We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP), Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients., Results: Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro , it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells., Conclusion: The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection., Methods: This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events., Discussion: To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Goto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Accumulating evidence demonstrates that the activity regulation of ELK3, a member of the E26 transformation-specific oncogene family, is critical to regulating cell proliferation, migration, and survival in human cancers. However, the molecular mechanisms of how ELK3 induces chemoresistance in prostate cancer (PCa) have not been elucidated. In this study, we found that SPOP and ELK3 are an interacting partner. The interaction between SPOP and ELK3 resulted in increased ELK3 ubiquitination and destruction, assisted by checkpoint kinase-mediated ELK3 phosphorylation. Notably, the modulation of SPOP-mediated ELK3 protein stability affected the c-Fos-induced cell proliferation and invasion of PCa cells. The clinical involvement of the SPOP-ELK3 axis in PCa development was confirmed by an immunohistochemical assay on 123 PCa tissues, with an inverse correlation between increased ELK3 and decreased SPOP being present in ~80% of the specimens. This observation was supported by immunohistochemistry analysis using a SPOP-mutant PCa specimen. Finally, docetaxel treatment induced cell death by activating checkpoint kinase- and SPOP-mediated ELK3 degradation, while SPOP-depleted or SPOP-mutated PCa cells showed cell death resistance. Notably, this observation was correlated with the protein levels of ELK3. Taken together, our study reveals the precise mechanism of SPOP-mediated degradation of ELK3 and provides evidence that SPOP mutations contribute to docetaxel resistance in PCa., (© 2024. The Author(s).)

Background: Delivery of cancer treatments, such as chemotherapy, requires a complex set of decisions that can change over time. Traditional measures of chemotherapy delivery, such as relative dose intensity, measure the amount of chemotherapy received by the end of treatment but mask the timing of dose reductions, delays, and discontinuation. These events may be important for delivering timely interventions to support adherence and lower the risk of recurrence., Materials and Methods: We used an institutional database to identify women diagnosed with stage I-III breast cancer receiving adjuvant chemotherapy with a standard 4-cycle regimen of docetaxel + cyclophosphamide (TC, every 21 days) from April 2014 to December 2019. LCD was calculated as the amount of a given chemotherapy agent delivered at a specified time, t, divided by the total planned standard chemotherapy dose at time t. We visualized LCD curves for each chemotherapy agent and reported the median LCD and interquartile range (IQR) at the end of the regimen, overall and by age group (<65 years vs. 65+ years)., Results: The study population included 80 women. At the end of treatment, overall median LCDs for both cyclophosphamide and docetaxel were 100% (IQR: 99.6%, 100%), suggesting that TC was well tolerated. However, the lower quartile LCD for cyclophosphamide was 98.7% in older women treated with TC compared with 99.7% in younger women., Conclusion: Within our cohort, adjuvant TC was well tolerated with LCD curves showing largely on-time and full-dose administration. Subgroup analyses showed only slight decreases in adjuvant TC LCD for patients aged 65+ versus <65 years., (© The Author(s) 2024. Published by Oxford University Press.)

Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Neoadjuvant chemotherapy (NCT) has become an increasingly popular approach in management of breast cancer (BC). This study was conducted to evaluate the pathologic response and 36-month recurrence and survival rates of patients with human epidermal growth factor receptor 2 (HER2)-negative BC treated with different NCT regimens., Methods: A total of 163 female patients with HER2-negative BC who received NCT during 2017-2020 were identified from the Clinical Breast Cancer Registry of Iran and entered the study. The prescribed NCT regimens included 4 cycles of doxorubicin plus cyclophosphamide, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of paclitaxel, 4 cycles of doxorubicin plus cyclophosphamide followed by 4 cycles of docetaxel or 6 cycles of doxorubicin plus cyclophosphamide plus docetaxel (TAC)., Results: Thirty-two patients (19.6%) experienced pathologic complete response (pCR). TAC regimen, triple negative-BC and ki67>10% were significantly associated with increased pCR. The recurrence, overall survival (OS) and disease-free survival (DFS) rate at 36 months for all patients were 16.6%, 84.7% and 79.8%, respectively. Type of neoadjuvant regimen as well as age, hormone receptor status, Ki67, grade, clinical stage, type of surgery and pathologic response to chemotherapy did not significantly influence the survival and recurrence; however, TAC results in improved recurrence, OS and DFS rates., Conclusion: This study provides further evidence that NCT is a viable treatment option for patients with HER2-negative BC. The TAC regimen resulted in a significantly higher pCR rate compared to other regimens, but did not result in a significant improvement in recurrence, OS and DFS and rates., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer., Methods: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate., Results: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status., Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs) for biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) patients., Methods: Studies published in English up to May 2023 were identified in PubMed, Web of Science and ASCO-GU 2023. Studies accessing the efficacy and safety of second-line systematic therapies after first-line ARTs for biomarker-unselected mCRPC patients were eligible for current systematic review and network meta-analysis (NMA)., Results: Thirty-two studies with 5388 patients and 10 unique treatment modalities met our inclusion criteria. Current evidence suggested that docetaxel (DOC) combined with the same ART as first-line (ART1) (ART1 + DOC) were associated with significantly improved PSA response, PSA progression-free survival (PFS) and clinical or radiographic PFS (rPFS) compared with other reported second-line systematic therapies, including DOC. An increase in toxicity was observed with ART1 + DOC. Our NMA indicated that DOC monotherapy was only inferior to ART1 + DOC in improvement disease outcomes. The incidence of toxicity between patients received second-line DOC and an alternative ART (ART2) was similar., Conclusion: The available evidence reviewed in our work suggested a clinical benefit of DOC nomotherapy and DOC plus ART1 as the second-line systematic therapy for biomarker-unselected mCRPC patients progressed on a first-line ART. More studies and RCTs are needed to evaluate the optimal second-line treatments for mCRPC patients with one prior first-line ART., Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Preoperative chemoradiation (CRT) is expected to increase the rate of curative resection and complete histological response. In this trial, we investigated the efficacy of a neoadjuvant CRT regimen in gastric adenocarcinoma (NCT01565109 trial)., Materials and Methods: Patients with stage IB to IIIC gastric adenocarcinoma, endoscopy ultrasound and computed tomography-scan diagnosed, were eligible for this phase II trial. Neoadjuvant treatment consisted of 2 cycles of chemotherapy with DCF (docetaxel, cisplatin, and 5-fluorouracil [5FU]) followed by preoperative CRT with oxaliplatin, continuous 5FU and radiotherapy (45 Gy in 25 fractions of 1.8 Gy, 5 fractions per week for 5 weeks) administered before surgery. R0-resection rate, pathological complete response (pathCR) rate, and survival (progression-free survival [PFS] and overall survival [OS]) were evaluated as primary endpoints., Results: Among 33 patients included, 32 patients (97%) received CRT and 26 (78.8%) were resected (R0 resection for all patients resected). Among resected patients, we report pathCR in 23,1% and pathologic major response (tumor regression grade 2 according to Mandard's classification) in 26,9%. With a median follow-up duration of 5.82 years (range, 0.4 to 9.24 years), the estimated median OS for all 33 patients was not reached; 1-, 3-, and 5-year OS rates were 85%, 61%, and 52%, respectively. Among resected patients, those whose histological response was tumor grade regression (TRG) 1-2 had significantly better OS and PFS rates than those with a TRG 3-4-5 response (p=0.019 and p=0.016, respectively)., Conclusion: Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer need to be further evaluated in a phase III trial.

Purpose: To understand the treatment plans suggested for BCG-unresponsive non-muscle invasive disease (NMIBC) patients in the Arab countries and therapeutic decisions applied for BCG-naive patients during BCG shortage time., Methods: A 10-minute online survey was distributed through the Arab Association of Urology (AAU) office to urologists in the Arab countries who treat patients with NMIBC., Results: One hundred six urologists responded to the survey. The majority of urologists had treated, in the past 6 months, > 10 patients with NMIBC who were considered BCG-unresponsive (55% of respondents). Radical cystectomy (RC) was the most popular treatment option (recommended by 50%) for these patients. This was followed by intravesical chemotherapy (30%), repeat BCG therapy (12%), resection with ongoing surveillance (8%). Clinical trials and intravenous checkpoint inhibitors were never selected. The most preferred intravesical chemotherapy was by ranking: 60% gemcitabine, 19% mitomycin C, 8% docetaxel, 8% gemcitabine/docetaxel, 4% sequential gemcitabine/mitomycin C, and 1% valrubicin. The use of intravesical chemotherapy appears limited by Arab urologists due to concerns regarding clinical efficacy (fear of progression) and the lack of clear recommendations by urology societies. Given the BCG shortage, which may vary per Arab country, Arab urologists have adjusted by prioritizing BCG for T1 and carcinoma in situ (CIS) patients over Ta, adapting intravesical chemotherapy, and reducing the dose/strength of BCG administered. Most physicians report an eagerness to utilize novel therapies to address the BCG deficit, especially to try intravesical chemotherapy., Conclusions: Even though Arab urologists are in the majority of cases selecting RC for BCG-unresponsive cases, one-third of them are most recently initiating intravesical chemotherapy as an alternative option. To further assist Arab urologists in the appropriate selection of BCG unresponsive high risk NMIBC patient treatments, enhanced education and pathway protocols are needed.

The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months' median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32-0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30-0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population., (© 2024. The Author(s).)