Current oncology最新文献

Introduction: The optimal treatment of estrogen receptor-positive (ER +) metastatic breast cancer (MBC) after progression on cyclin-dependent 4/6 kinase inhibitors (CDK4/6i) is unknown.

Methods: We conducted a systematic review and network meta-analysis (NMA) of phase-II/-III randomized trials of ER + MBC post CDK4/6i + ET progression. We calculated the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) using generic inverse variance and odds ratios (ORs) using the Mantel-Haenszel method for adverse events (AEs) with Review-Manager version-5.4. NMA was executed using WINBUGS (Microsoft Excel). Three molecular subgroups were analyzed: HER2-low, PI3K/AKT/mTOR, and the ESR1 mutation subgroup for selective estrogen receptor degrader (SERD).

Results: A total of 14 studies were included. In the HER2-low group, Sacituzumab govitecan and trastuzumab deruxtecan had a similar efficacy (HR, 95% CI): PFS (0.98; 0.63-1.43) and OS (1.08; 0.76-1.55). In PI3K/AKT/mTOR-altered cases, capivasertib was superior to alpelisib PFS (0.77; 0.53-1.12), and OS (0.80; 0.48-1.35). SERDs had worse PFS and OS versus ongoing CDK 4/6i (ribociclib).

Conclusion: No therapy emerged as the unequivocal choice in the post-CDK 4/6i domain in unselected subgroups. In the HER2-low population, a similar efficacy and different toxicity spectrum was seen. In AKT-altered tumors, capivasertib was less toxic than alpelisib.

Prospero id: CRD4202236412.

Patients with endometrial neoplasia (EN) often have multiple comorbidities and a higher surgical risk. Prehabilitation programs (PPs) combine various interventions to improve preoperative conditions and reduce impairment due to surgical stress. We conducted a pragmatic pilot study to evaluate the acceptability and feasibility of a trimodal telehealth PP (exercise, nutrition, and psychological support) for EN patients. The participants could select their exercise group: (1) a supervised PP (SPP), group sessions 3×/week; (2) a semi-supervised PP (SSPP), group session 1×/week, training alone 2×/week; or (3) a physical activity counseling session (PACS). Out of the 150 EN patients awaiting surgery screened during the 18 months of the study recruitment, 66% (99/150) were eligible, and 40% consented to participate (SPP, n = 13; SSPP, n = 17; PACS, n = 9). The overall dropout was low (13%; 5/39), with no significant differences across groups. No serious adverse events occurred. We observed a positive impact on different outcomes across the different groups, such as in the Functional Assessment of Cancer Therapy quality of life score (SPP; delta = 6.1 [CI: 0.9; 12.6]) and functional capacity measured using the 30″ sit-to-stand test (PACS delta = 2.4 [CI: 1.2; 3.6]). The same-day hospital leave was high in the SSPP group (54.5%). Our pilot telehealth PP seems to be safe, feasible, and well accepted and may procure clinical and patient-centered gains that need to be confirmed in a larger trial.

Introduction: CDK4/6 inhibitors in combination with aromatase inhibitors (AIs) are the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer. Landmark trials have demonstrated a comparable progression-free survival (PFS) across CDK4/6 inhibitors, but the overall survival (OS) outcomes have varied. This study aimed to evaluate the real-world PFS and OS for palbociclib and ribociclib when combined with AIs in patients with HR+/HER2- advanced breast cancer.

Materials and methods: This was a retrospective chart review of adult patients with HR+/HER2- metastatic breast cancer treated at a single academic center between 1 January 2015 and 1 December 2022. The baseline demographics, clinical characteristics, and treatment details were extracted. A Kaplan-Meier analysis was used to estimate the PFS and OS, and differences between the treatment groups were assessed using the log-rank test. Cox proportional hazards models were constructed to adjust for confounding factors.

Results: Seventy-five patients were included in the final analysis. The cohort was predominantly female (98.7%) and postmenopausal (77.3%), with 52.0% having de novo stage IV disease. Palbociclib was prescribed to 74.7% of the patients, and ribociclib to 25.3%. The patients receiving ribociclib were significantly younger (57.6 vs. 67.5 years, p = 0.013) and more likely to be premenopausal (42.1% vs. 5.4%, p < 0.001). The real-world median PFS and OS for palbociclib were 20.3 months (95% CI: 14.8-46) and 37.2 months (95% CI: 20.3-not reached [NR]), respectively. For ribociclib, the median PFS and OS were not reached. The Cox proportional hazards models adjusting for age and menopausal status found no significant differences between ribociclib and palbociclib for the PFS (HR = 0.92, p = 0.86) or OS (HR = 0.95, p = 0.92).

Conclusion: In this real-world analysis, palbociclib demonstrated a median PFS consistent with the results from landmark trials, although the observed OS was shorter. The ribociclib-treated patients had a numerically longer PFS and OS compared with those treated with palbociclib, but the differences were not statistically significant. The discontinuation rates were similar between the two groups.

(1) Background: MicroRNA-129 (miR-129) participates in tumor progression and chemoresistance in various cancer types. In this study, the role of miR-129-3p, the main mature form of miR-129, in tumor progression and chemoradiotherapy resistance in head and neck cancer was evaluated. (2) Methods: RT-PCR, western blotting, cell proliferation assays, cell apoptosis assays, and cell invasion and migration assays were used. (3) Results: In this study, the miR-129-3p overexpression suppressed the proliferation, invasion, and migration of SNU1041, SCC15, and SCC25 human HNSCC cell lines. Additionally, it induced apoptosis and enhanced radiation-/cisplatin-induced apoptosis of SNU1041, SCC15, and SCC25 cells. Therefore, miR-129-3p could suppress tumor progression and enhance chemoradiosensitivity in human HNSCC. Furthermore, miR-129-3p was downregulated in fresh tumor tissues from patients with HNSCC compared with that in the adjacent normal mucosa. In a nude mouse xenograft model with SNU15 cells, the miR-129-3p overexpression significantly decreased tumor growth, as measured by tumor weight and volume. (4) Conclusions: Our study provides evidence that miR-129-3p suppresses tumor progression and chemoradioresistance in HNSCC. This finding may serve as a basis for developing miR-129-3p-based therapeutic strategies.

The aim of this study was to evaluate associations between TP53 status and outcomes after transarterial embolization (TAE) for the treatment of patients with hepatocellular carcinoma (HCC). This single-institution study included patients from 1/2014 to 6/2022 who underwent TAE of HCC and genomic analysis of tumoral tissue. The primary outcome was overall survival (OS) with relation to TP53 status, and the secondary outcome was the time to progression. Survival analysis was performed using the Kaplan-Meier method. The time to progression with death or the last patient contact without progression as competing risks were used to obtain a cumulative incidence function, and the association with TP53 status was evaluated using the Gray test. In total, 75 patients (63 men) with a median age of 70.0 (IQR 62.0-76.3) years were included. Of these, 26/75 (34.7%) patients had TP53-mutant HCC. Patients with TP53-mutant HCC had a significantly worse median OS of 15.2 (95% CI, 9.5-29.3) months, versus 31.2 (95% CI, 21.2-52.4) months as the median OS (p = 0.023) for TP53 wild-type HCC. Competing risk analysis showed a shorter time to local hepatic progression (at the site of the previously treated tumor) after TAE in patients with TP53-mutant HCC. The cumulative incidences of local progression at 6 and 12 months for TP53-mutant HCC were 65.4% and 84.6%, versus 40.8% and 55.1% for TP53 wild-type HCC (p = 0.0072). A TP53 mutation may predict a worse overall survival and a shorter time to local progression in HCC patients treated with TAE.

Introduction: Pancreatic cancer (PC) is one of the most aggressive and lethal malignancies, calling for enhanced research. Pancreatic ductal adenocarcinoma (PDAC) represents 70-80% of all cases and is known for its resistance to conventional therapies. Carbon-ion radiotherapy (CIRT) has emerged as a promising approach due to its ability to deliver highly localized doses and unique radiobiological properties compared to X-rays. In vitro radiobiology has relied on two-dimensional (2D) cell culture models so far; however, these are not sufficient to replicate the complexity of the in vivo tumor architecture. Three-dimensional (3D) models become a paradigm shift, surpassing the constraints of traditional models by accurately re-creating morphological, histological, and genetic characteristics as well as the interaction of tumour cells with the microenvironment. Materials and Methods: This study investigates the survival of pancreatic cancer cells in both 2D and spheroids, a 3D model, following photon, proton, and carbon-ion irradiation by means of clonogenic, MTT, spheroid growth, and vitality assays. Results: Our results demonstrate that carbon ions are more efficient in reducing cancer cell survival compared to photons and protons. In 2D cultures, carbon-ion irradiation reduced cell survival to approximately 15%, compared to 45% with photons and 30% with protons. In the 3D culture model, spheroid growth was similarly inhibited by carbon-ion irradiation; however, the overall survival rates were higher across all irradiation modalities compared to the 2D cultures. Carbon ions consistently showed the highest efficacy in reducing cell viability in both models. Conclusions: Our research highlights the pivotal role of 3D models in unraveling the complexities of pancreatic cancer radiobiology, offering new avenues for designing more effective and precise treatment protocols.

Radiation-induced morphea (RIM) is a rare complication following radiotherapy (RT) for breast cancer treatment. Its distribution is usually confined to the breast having received radiotherapy. A generalized form of RIM also exists, defined as lesions extending beyond the radiotherapy site, but data on the subject are scarce in the literature. This complication remains difficult to treat, due partly to the variable extent of disease and to individual clinical response rates to the wide array of available therapies, such as topical therapy (i.e., topical tacrolimus or topical corticosteroids), phototherapy, and systemic therapy (i.e., systemic immunosuppressants). We present a case of extensive morphea post RT for breast cancer with 2 years of favorable evolution under systemic therapy.

Although the majority of patients with nasopharyngeal carcinoma (NPC) present with early-stage or locoregional disease that can be treated with definitive radiotherapy, approximately 20% of patients experience disease recurrence, and 15% present with metastatic disease that is not amenable to curative therapy. Management of patients with recurrent or metastatic (r/m) NPC who are not candidates for local salvage therapy is challenging in Canada, as there is uncertainty in extrapolating evidence that is largely generated from Southeast China to non-endemic regions such as Canada. Currently, treatment options in Canada are limited to chemotherapy regimens that can only achieve short-term response and prolongation of survival. The addition of anti-PD-1 monoclonal antibodies to chemotherapy has been shown to extend progression-free survival in recurrent r/m NPC compared to chemotherapy alone; however, approval of PD-1 inhibitors in Canada has lagged behind other jurisdictions where NPC is non-endemic. This paper reviews the current systemic treatment landscape for r/m NPC in Canada, highlights unmet treatment needs for patients who are not candidates for curative therapy, and discusses the challenges and opportunities that lie in emerging therapies.

Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations in cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with the ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As a result, pharmacologic inhibition of mIDH has become an attractive therapeutic strategy in CCAs harboring this mutation. One such inhibitor, ivosidenib, has already undergone clinical validation and received FDA approval in this disease, but there is still much work to be done to improve outcomes in mIDH CCA patients. In this publication we will review the pathogenesis and treatment of mIDH CCA with special emphasis on novel agents and combinations currently under investigation.

Background: Adjuvant endocrine therapy (AET) is prescribed for 5-10 years to women with hormone-sensitive breast cancer to prevent recurrence. However, a significant proportion of women do not adhere to AET. We developed SOIE, a one-year program designed to enhance the AET experience and adherence. SOIE was pilot-tested in a mixed-methods randomized controlled trial. This report presents the experience of women and healthcare providers (HCPs) with SOIE.

Methods: A descriptive qualitative study using semi-structured interviews and thematic analysis was conducted with 20 women and 7 HCPs who participated in the program.

Results: Most women and HCPs reported high satisfaction with the program. Women felt it addressed their need for information and strategies to manage side effects. They felt supported and developed a more positive attitude toward AET, which contributed to their intention to pursue AET. They perceived that the program helped them navigate the AET experience and reduced their stress or fear regarding AET. HCPs corroborated these benefits.

Conclusions: Findings suggest that SOIE can enhance the experience and motivation to pursue the AET treatment by meeting important needs for information, side-effects management, and psycho-emotional support. Programs like SOIE can have benefits beyond adherence by improving patients' well-being during this crucial long-term treatment.