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Cureus May 2024Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced...
Multimodality treatments, including chemotherapy, radiation, and surgery, have been evaluated to reduce the extent of resection and morbidity in patients with advanced vulvar cancer. Here, we report the case of a 55-year-old woman diagnosed with advanced vulvar cancer with inguinal and pelvic lymph node metastasis. She exhibited cancerous labia, which were entirely covered with ulcerated and exophytic lesions of squamous cell carcinoma, and underwent systemic chemotherapy consisting of combined paclitaxel-cisplatin. After eight cycles of this regimen, the tumors had nearly regressed, and we performed a wide local vulvectomy with a plastic musculocutaneous flap. Pathological examination revealed no residual carcinoma in the excised labia, indicating that the chemotherapy elicited a pathological complete response. The paclitaxel-cisplatin regimen may provide sufficient efficacy for selected patients with stage IVB vulvar cancer. In addition, surgical strategies should be tailored to avoid complications associated with extensive surgery and more emphasis should be placed on the patient's expected quality of life.
PubMed: 38882968
DOI: 10.7759/cureus.60432 -
Therapeutic Advances in Medical Oncology 2024In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the...
French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients.
CONTEXT
In France, gemcitabine plus nab-paclitaxel (GEM-NAB) is heterogeneously used in metastatic pancreatic cancer due to disparities in its financial accessibility in the institutions.
OBJECTIVES
GEM-NAB conduct a French multi-institutional cost-effectiveness analysis of GEM-NAB gemcitabine alone (GEM) as second-line treatment in pancreatic cancer patients.
DESIGN
All the unresected metastatic pancreatic ductal adenocarcinoma (PDAC) consecutive patients who received GEM-NAB (institution 1) or GEM alone (institutions 2 and 3) as second-line treatment after failure of a 5-fluorouracil based systemic chemotherapy regimen were screened.
METHODS
This study was conducted from the French national healthcare insurance perspective. The primary endpoint was the overall survival (OS) expressed in months, calculated from the date of the first second-line chemotherapy administration to death. Only direct (medical and non-medical) costs have been considered for this analysis. Data were collected retrospectively in one university hospital and two general hospitals.
RESULTS
The OS was significantly improved in patients receiving GEM-NAB (hazard ratio: 0.54, 95% confidence interval: 0.38-0.77, = 0.001), with a median OS of 6.2 months ( 4.1 months in patients receiving GEM alone). Taking into account the cost of GEM-NAB which was afforded by each institution, the incremental cost-effectiveness ratio was €1,449,231 by year of life (€40,256 per patient). In both groups, most of the costs were attributable to readmissions and outpatient chemotherapy administration.
CONCLUSION
The issues of the article is based on the trade-off between the benefit in terms of OS of patients treated with GEM-NAB, which is minor (a gain of 2 months of survival, with an accumulated rate of grade ⩾ 3 non-hematological adverse effects) and the additional institutional cost (€25k per year of life for each patient treated). The debate is complex and refers to an ethical component, which is the cost of human life when no other therapeutic alternative is offered to the patient.
PubMed: 38882442
DOI: 10.1177/17588359241259635 -
Translational Cancer Research May 2024Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase...
BACKGROUND
Chidamide (CHI) is a subtype-selective histone deacetylase inhibitor (HDACI) developed in China and approved as a second-line treatment combined with the aromatase inhibitor for hormone receptor-positive (HR)/human epidermal growth factor receptor 2-negative (HER2) advanced breast cancer. However, drug resistance is commonly occurred after a long period of medication. This study aimed to investigate the characterization of induced resistance to CHI and explore the potential cross-resistance to chemotherapeutic agents.
METHODS
CHI with gradually increasing concentrations was added to breast cancer MCF7 cells to establish a CHI-resistant MCF7 (MCF7-CHI-R) cell line. Cell counting kit-8 (CCK-8) assays were performed to detect half-maximal inhibitory concentration (IC) of CHI. Colony formation was used to determine the proliferation inhibition rate. Western blot analysis was conducted to detect expressions of protein related with cell cycle, apoptosis, ferroptosis, and histone deacetylase (HDAC). Flow cytometry was used to analyze apoptosis and cell cycle.
RESULTS
The IC value of CHI of MCF7-CHI-R cells was increased in comparison with MCF7 cells. And CHI led to cell cycle arrest and ferroptosis, which were not exhibited in MCF7-CHI-R cells. Moreover, HDAC activity decreased in MCF7-CHI-R cells in comparison with MCF7 cells, and HDAC1 and HDAC10 might be involved in the resistance to CHI. In addition, MCF7-CHI-R cells were resistant to gemcitabine (GEM), doxorubicin (ADM), docetaxel (DXT), albumin-bound paclitaxel (nab-PTX) and paclitaxel (PTX).
CONCLUSIONS
The MCF7-CHI-R was established and the anti-ferroptosis pathway activation was involved in the resistance of MCF-CHI-R cells. Also, MCF7-CHI-R cells were resistant to GEM, ADM, DXT, nab-PTX and PTX.
PubMed: 38881946
DOI: 10.21037/tcr-23-2169 -
Translational Cancer Research May 2024Lactylation has been found to regulate several types of biological processes in cancer. However, there is limited research on lactylation-related genes in predicting the...
BACKGROUND
Lactylation has been found to regulate several types of biological processes in cancer. However, there is limited research on lactylation-related genes in predicting the prognosis of ovarian cancer (OC). This study aimed to explore the functional roles of lactylation-related genes in OC.
METHODS
Based on TCGA database, we obtained RNA sequencing data and clinical characteristics of patients with OC. Fourteen lactylation-related genes were screened for bioinformatic analysis in OC. Tumor classification of OC was constructed via a consistency cluster analysis. We examined the prognosis, immune-cell infiltration, and immunotherapy in relation to a lactylation-related model for OC.
RESULTS
A total of 707 prognostic genes and 14 key lactylation-related genes (, , , , , , , , , , , , , and ) were identified in TCGA-OC patients. Based on 14 genes involved in lactylation, TCGA-OC patients were split into low-risk (G1) and high-risk (G2) groups. Downregulated differentially expressed genes (DEGs) in the low-risk G1 group were associated with thermogenesis, oxidative phosphorylation, neutrophil extracellular trap formation, and interleukin 17 (IL-17) signaling pathway, whereas upregulated DEGs were associated with proteoglycans in cancer, focal adhesion, Wnt signaling pathway, extracellular matrix (ECM)-receptor interaction, and the adherens junction. The immune activity of the low-risk G1 group was lower than that of the high-risk G2 group. Gemcitabine, bleomycin, and doxorubicin had lower half-maximal inhibitory concentration (IC) values in the high-risk G2 patients with OC, while cisplatin and paclitaxel had higher IC values compared to the low-risk G1 patients. The prognosis of patients with OC was also predicted with the help of an eight-lactylation-related gene prognostic model, comprising , , , , , , , and
CONCLUSIONS
The lactylation-related genes are closely related to tumor classification and immunity in patients with OC. There was good prognostic predictive performance for OC based on a lactylation-related signature. Our findings may offer new insights into the diagnosis and treatment of OC.
PubMed: 38881917
DOI: 10.21037/tcr-24-319 -
Oncology Letters Aug 2024Small bowel adenocarcinoma (SBA) is a rare tumor with a poor prognosis. Due to its rarity, the research infrastructure for SBA, including cell lines, is inadequate. The...
Small bowel adenocarcinoma (SBA) is a rare tumor with a poor prognosis. Due to its rarity, the research infrastructure for SBA, including cell lines, is inadequate. The present study established a novel SBA cell line, SiCry-15X, using patient-derived xenografts of SBA. The following criteria were defined for establishment: Long-term culturability, tumorigenicity and similarity with the original tumor. The biological characteristics of the cell line, its sensitivity to anticancer drugs and its ability to produce tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were evaluated. SiCry-15X cells adhered and grew as a monolayer, with a population doubling time of 37 h. Polymerase chain reaction results confirmed the human origin of the cell line, and short tandem repeat analysis revealed that the cells were genetically identical to the original tumor. The 50% inhibitory concentrations of 5-fluorouracil, paclitaxel, irinotecan, oxaliplatin and cisplatin for SiCry-15X were 104.05, 0.24, 63.3, 146.55 and 49.29 µM, respectively. CEA and CA19-9 concentrations in the culture media were markedly elevated. In addition, CEA and CA19-9 levels in the serum of cell-derived xenograft model mice were elevated. Moreover, CEA and CA19-9 were produced by SiCry-15X cells and distributed throughout the blood. Furthermore, increases in serum CEA and CA19-9 of cell-derived xenograft model mice were consistent with the clinical course of the disease. The newly established SBA cell line, SiCry-15X, could be an effective tool for conducting further studies on SBA.
PubMed: 38881709
DOI: 10.3892/ol.2024.14493 -
Experimental and Therapeutic Medicine Aug 2024[This retracts the article DOI: 10.3892/etm.2017.5588.].
[This retracts the article DOI: 10.3892/etm.2017.5588.].
PubMed: 38873044
DOI: 10.3892/etm.2024.12598 -
Oncology Letters Aug 2024Gastric-type endocervical adenocarcinoma (GEA) is an uncommon and highly aggressive malignancy, characterized by non-specific clinical manifestations. The limited number...
Gastric-type endocervical adenocarcinoma (GEA) is an uncommon and highly aggressive malignancy, characterized by non-specific clinical manifestations. The limited number of documented cases poses significant challenges in achieving an early preoperative diagnosis. In the present study, two cases of GEA in female patients, aged 46 and 39 years, who presented with the chief complaint of profuse vaginal discharge are described. Both patients underwent a total hysterectomy and bilateral adnexectomy, leading to the definitive diagnosis of GEA through routine pathological and immunohistochemical examination. Following surgery, case one received conventional chemotherapy with paclitaxel and carboplatin, demonstrating no evidence of recurrence during a follow-up period of >2 years. At present, patient B has been followed up for >1 year without any signs of disease recurrence. Given the rarity and diagnostic challenges associated with GEA, further investigations into its pathogenesis and diagnostic modalities are warranted. Additionally, due to its poor prognosis, close surveillance is essential for monitoring potential recurrences. Reporting such cases is crucial in aiding clinicians to make accurate diagnoses and treatment decisions.
PubMed: 38872865
DOI: 10.3892/ol.2024.14477 -
Oncology Letters Aug 2024Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment...
Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment methods shrink the tumor and relieve symptoms. The present study reports a rare case of advanced ovarian cancer with skin metastases and intestinal wall thickening, along with a BRCA1 DNA repair associated (BRCA1) mutation. After standard first-line treatment and non-standard second-line treatment, the patient developed skin metastases. The patient's skin itching, pain and lesions were completely relieved after administering bevacizumab in combination with paclitaxel and carboplatin. After 4 months, skin metastases recurred along with anal distension during maintenance treatment with oral poly(ADP ribose) polymerase (PARP) inhibitors. The patient was treated again with bevacizumab combined with docetaxel, and the anal distension was significantly relieved. Angiogenesis therapy combined with chemotherapy is effective, but that the disease-free survival time is short, and PARP inhibitor maintenance effect is limited even in cases with a BRCA1 gene mutation.
PubMed: 38872856
DOI: 10.3892/ol.2024.14481 -
International Journal of Cardiology.... Sep 2024Acute cardiac complications post-chemotherapy is rare. Stress cardiomyopathy, one of these complications, should be considered in differential diagnoses as its symptoms...
BACKGROUND
Acute cardiac complications post-chemotherapy is rare. Stress cardiomyopathy, one of these complications, should be considered in differential diagnoses as its symptoms closely resemble those of acute myocardial infarction and can lead to mortality.
OBJECTIVE
The objective of this paper is to describe Takotsubo syndrome (TTS) as an acute complication following combined chemotherapy in a patient with significant thromboembolic burden and metastatic cervical cancer.
CASE
A 61-year-old female patient with a diagnosis of metastatic cervical cancer experienced acute chest pain. Elevated troponin levels and abnormalities in the electrocardiogram initially suggested an acute myocardial infarction, occurring after a chemotherapy session involving Carboplatin and Paclitaxel infusion. Although initial treatment targeted myocardial infarction, further diagnostic evaluations including coronary angiography and cardiac magnetic resonance imaging revealed no coronary artery disease but identified features consistent with stress cardiomyopathy, indicative of Takotsubo syndrome (TTS). This diagnosis led to an improvement in symptoms and a resolution of the acute changes observed.
CONCLUSION
Stress cardiomyopathy, particularly TTS, is being increasingly recognized as an acute complication associated with combined chemotherapy regimens. The potential cardiotoxic effects of these chemotherapy agents demand careful monitoring and evaluation in patients undergoing oncological treatment, underscoring the importance of integrating cardioprotective strategies into the management of these patients.
PubMed: 38872732
DOI: 10.1016/j.ijcrp.2024.200292 -
Journal of Gynecologic Oncology Apr 2024First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global...
First-line bevacizumab plus chemotherapy in Chinese patients with stage III/IV epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer: a phase III randomized controlled trial.
OBJECTIVE
First-line bevacizumab plus carboplatin and paclitaxel (CP) is approved for stage III/IV ovarian cancer treatment following initial surgical resection, based on global phase III GOG-0218 and ICON7 trials. This study evaluated the efficacy and safety of bevacizumab + CP as first-line ovarian cancer therapy in Chinese patients.
METHODS
Patients with newly diagnosed, International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian, fallopian tube, or primary peritoneal cancer post-primary surgery were randomized 1:1 to receive 6 cycles of CP with bevacizumab/placebo, followed by bevacizumab/placebo maintenance until unacceptable toxicity or disease progression. Primary endpoint was investigator-assessed progression-free survival (PFS). Stratification factors were FIGO stage and debulking status (stage III optimally debulked vs stage III suboptimally debulked vs stage IV) and Eastern Cooperative Oncology Group performance status (0 vs 1 or 2).
RESULTS
Of randomized patients, 51 received bevacizumab + CP and 49 received placebo + CP. Median PFS was 22.6 months with bevacizumab + CP (95% confidence interval [CI]=18.6, not estimable) and 12.3 months (95% CI=9.5, 15.0) with placebo + CP (stratified hazard ratio=0.30; 95% CI=0.17, 0.53). Treatment-related grade 3/4 adverse events occurred in 46 of 49 (94%) patients receiving bevacizumab + CP, and 34 of 50 (68%) receiving placebo + CP.
CONCLUSION
Bevacizumab + CP showed clinically meaningful improvement in PFS vs placebo + CP, consistent with GOG-0218 results. Safety data were aligned with the known bevacizumab safety profile. These results support first-line bevacizumab + CP therapy in Chinese patients with ovarian cancer.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03635489.
PubMed: 38872480
DOI: 10.3802/jgo.2024.35.e99