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European Journal of Cancer (Oxford,... Sep 2019In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10)... (Comparative Study)
Comparative Study
BACKGROUND
In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10) or diffuse (n = 19) anaplastic Wilms' tumour (AWT) treated with vincristine and dactinomycin without flank radiation were 69.5% and 82.6%, respectively. The Children's Oncology Group AREN0321 study evaluated whether adding doxorubicin and flank radiation improves survival for these patients.
PATIENTS AND METHODS
Tumour histology and stage were confirmed by real-time central pathology, surgery and radiology review. The patients received 25 weeks of vincristine, dactinomycin and doxorubicin (cumulative dose 150 mg/m) with flank radiation (1080 cGy). We retrospectively analysed outcomes of all patients with stage I AWT enrolled in NWTSs 1-5 and AREN0321 with respect to treatment regimens.
RESULTS
Eighteen patients with stage I AWT (8 focal and 10 diffuse) were enrolled on AREN0321. With a median follow-up of 4.6 years, the 4-year EFS and OS were 100%. One patient with diffuse AWT had pulmonary relapse 4.12 years after diagnosis. In the 112 patients with stage I AWT treated in NWTSs 1-5 and AREN0321, the EFS was significantly improved with doxorubicin treatment (p = 0.01; 4-year EFS: 97.2% [95% confidence interval {CI}: 91.3-100] vs. 77.5% [95% CI: 67.6-87.4]) but not by flank radiation (p = 0.15).
CONCLUSIONS
Treatment of stage I AWT with vincristine, dactinomycin, doxorubicin and flank radiation in AREN0321 yielded excellent survival outcomes. Retrospective analysis of AREN0321 and NWTS patients suggests that doxorubicin had a greater contribution to the excellent outcomes than radiation.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Child, Preschool; Dactinomycin; Disease Progression; Doxorubicin; Female; Humans; Infant; Kidney Neoplasms; Male; Neoplasm Staging; Nephrectomy; Progression-Free Survival; Radiotherapy, Adjuvant; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; United States; Vincristine; Wilms Tumor
PubMed: 31325873
DOI: 10.1016/j.ejca.2019.05.033 -
Surgical Oncology Sep 2021Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be...
BACKGROUND AND OBJECTIVES
Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department.
PATIENTS AND METHODS
Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months.
RESULTS
The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1-219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016).
CONCLUSION
HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Extremities; Female; Follow-Up Studies; Humans; Hyperthermia, Induced; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 33992896
DOI: 10.1016/j.suronc.2021.101603 -
Efficacies of FAEV and EMA/CO regimens as primary treatment for gestational trophoblastic neoplasia.British Journal of Cancer Aug 2022Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Guidelines recommend etoposide, methotrexate, actinomycin D (EMA)/cyclophosphamide, vincristine (CO) as first-line treatment for high-risk gestational trophoblastic neoplasia (GTN). However, the floxuridine, actinomycin D, etoposide and vincristine (FAEV) regimen is commonly used to treat these patients in China. We conducted a randomised controlled trial to compare the efficacies and toxicities of FAEV and EMA/CO.
METHODS
Ninety-four patients with GTN were enrolled between May 2015 and April 2019 and randomly assigned to the FAEV or EMA/CO regimen. The rates of complete remission and relapse and the toxicities were compared in August 2021.
RESULTS
Five patients were excluded from the analysis. There were 46 patients in the FAEV group and 43 patients in the EMA/CO group. The complete remission rates following primary treatment were 89.1% and 79.1% (P = 0.193), respectively. The relapse rates were 8.7% and 9.3% (P = 0.604). The apparent incidences of grade 4 myelosuppression were 60.9% and 32.6% (P = 0.008), respectively; however, they became both 32.6% (P = 0.996) after granulocyte colony-stimulating factor support. Other adverse reactions were similar in the two groups. No patient died of disease.
CONCLUSION
FAEV has comparable efficacy and toxicity to EMA/CO as the primary treatment for high-risk GTN, and may thus be another first-line choice of chemotherapy.
CLINICAL TRIAL REGISTRATION
chictr.org.cn: ChiCTR1800017423.
Topics: Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Etoposide; Female; Floxuridine; Gestational Trophoblastic Disease; Humans; Neoplasm Recurrence, Local; Pregnancy; Vincristine
PubMed: 35459802
DOI: 10.1038/s41416-022-01809-3 -
Clinical Case Reports Oct 2023Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are...
KEY CLINICAL MESSAGE
Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.
ABSTRACT
Choriocarcinoma is a malignant epithelial tumor of the chorionic villi that often manifests after a normal or molar pregnancy. The primary tubal choriocarcinoma associated with ectopic pregnancy is extremely rare and can be misdiagnosed as an ectopic pregnancy since symptoms including vaginal bleeding, amenorrhea, elevated beta-human chorionic gonadotropin (BHCG) levels, and pelvic pain are shared. A 34-year-old G4P3003 woman presented with a one-week history of vaginal bleeding and right lower abdominal pain, which had intensified a day before admission. Clinical and paraclinical examinations pointed to a ruptured tubal pregnancy; hence, an emergency laparotomy was performed, and a right salpingectomy was carried out on the patient. However, a nonsignificant decline in BHCG level was observed, and histological examination revealed tubal choriocarcinoma; hence, a metastasis workup was carried out, yet no metastasis was detected. Six sessions of chemotherapy consisting of Etoposide, Methotrexate, Dactinomycin, Cyclophosphamide, and Vincristine (EMA-CO) were administered without complication, in such a way that the BHCG level normalized after three sessions of chemotherapy. Evaluations after 1 year from the completion of chemotherapy revealed that the patient had no subsequent problems. Choriocarcinoma of the fallopian tube is extremely rare and highly susceptible to early metastasis. Clinical manifestations of ectopic pregnancy and choriocarcinoma are the same, and all patients with ectopic pregnancy should be evaluated for choriocarcinoma based on histopathological findings. Metastasis workup should be considered for all individuals with choriocarcinoma. Adjuvant chemotherapy (after surgery) is the proposed treatment for tubal choriocarcinoma.
PubMed: 37780932
DOI: 10.1002/ccr3.7977 -
The Journal of Gene Medicine Jan 2024Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered...
INTRODUCTION
Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered programmed cell death process, is linked to the actin cytoskeleton, which plays a vital role in maintaining cell shape and survival. The role of disulfidptosis is poorly depicted in the clear cell histologic variant of RCC (ccRCC).
METHODS
Three sets of ccRCC cohorts, ICGC_RECA-EU (n = 91), GSE76207 (n = 32) and TCGA-KIRC (n = 607), were included in our study, the batch effect of which was removed using the "combat" function. Correlation was calculated using the "rcorr" function of the "Hmisc" package for Pearson analysis, which was visualized using the "pheatmap" package. Principal component analysis was performed by the "vegan" package, visualized using the "scatterplot3d" package. Long non-coding RNAs (lncRNAs) associated with disulfidptosis were screened out using least absolute shrinkage and selection operator (LASSO) and COX analysis. Tumor mutation, immune landscaping and immunotherapy prediction were performed for further characterization of two risk groups.
RESULTS
A total of 1822 disulfidptosis-related lncRNAs was selected, among which 308 lncRNAs were found to be significantly associated with the clinical outcome of ccRCC patients. We retained 11 disulfidptosis-related lncRNAs, namely, AP000439.3, RP11-417E7.1, RP11-119D9.1, LINC01510, SNHG3, AC156455.1, RP11-291B21.2, EMX2OS, AC093850.2, HAGLR and RP11-389C8.2, through LASSO and COX analysis for prognosis model construction, which displayed satisfactory accuracy (area under the curve, AUC, values all above 0.6 in multiple cohorts) in stratification of ccRCC prognosis. A nomogram model was constructed by integrating clinical factors with risk score, which further enhanced the prediction efficacy (AUC values all above 0.7 in multiple cohorts). We found that patients of male gender, higher clinical stages and advanced pathological T stage were inclined to have higher risk score values. Dactinomycin_1911, Vinblastine_1004, Daporinad_1248 and Vinorelbine_2048 were identified as promising candidate drugs for treating ccRCC patients of higher risk score value. Moreover, patients of higher risk value were prone to be resistant to immunotherapy.
CONCLUSION
We developed a prognosis predicting model based on 11 selected disulfidptosis-related lncRNAs, the efficacy of which was verified in different cohorts. Furthermore, we delineated an intricate portrait of tumor mutation, immune topography and pharmacosensitivity evaluations within disparate risk stratifications.
Topics: Humans; Male; Carcinoma, Renal Cell; RNA, Long Noncoding; Prognosis; Apoptosis; Kidney Neoplasms
PubMed: 37897262
DOI: 10.1002/jgm.3608 -
Archives of Gynecology and Obstetrics Apr 2022The aim of this study was to investigate the diagnosis, treatment, and prognosis of patients with brain metastases from gestational trophoblastic neoplasia (GTN) in the... (Review)
Review
OBJECTIVE
The aim of this study was to investigate the diagnosis, treatment, and prognosis of patients with brain metastases from gestational trophoblastic neoplasia (GTN) in the real world.
METHODS
Analyzing the clinicopathological characteristics, treatment process, and prognosis of 14 GTN patients with brain metastases admitted to the West China Second University Hospital between January 2006 and December 2020.
RESULTS
The median FIGO prognostic score was 15 points (range 11-21 points), with 12 cases having 13 points or more (extremely high risk). All patients received combination chemotherapy. The first-line regimen included 5-Fluorouracil, dactinomycin, and intrathecal methotrexate (5-FU + KSM + intrathecal MTX), and etoposide + methotrexate + actinomycin D/cyclophosphamide and vincristine (EMA-CO). Two patients died during the early period after diagnosis of brain metastases. A further patient with GTN Stage III failed to achieve a negative serum β human chorionic gonadotropin (hCG) after receiving chemotherapy in another hospital. Ten months after self-discontinuation of treatment, the disease progressed and she was admitted to our hospital with suspected liver and brain metastases, after which she abandoned treatment and was lost to follow-up. Among the remaining 11 patients, one relapsed once and two relapsed three times. Aside from the two patients who died and the one who was lost to follow-up, the remaining 11 patients had a median follow-up time of 89 months (range 35-148 months) and all achieved complete remission.
CONCLUSION
The overall survival rate of the patients in the present study was 78.57% through combination chemotherapy, symptomatic treatment, and co-treatment with brain radiotherapy for some patients. Enhancing the understanding of this disease and standardizing treatment are key to improving the overall survival rate of GTN patients with brain metastases.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chorionic Gonadotropin, beta Subunit, Human; Cyclophosphamide; Dactinomycin; Female; Gestational Trophoblastic Disease; Humans; Methotrexate; Pregnancy; Retrospective Studies
PubMed: 34542678
DOI: 10.1007/s00404-021-06238-w -
Frontiers in Oncology 2024Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or unfolded proteins within the cell and is intricately linked to the initiation and...
BACKGROUND
Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or unfolded proteins within the cell and is intricately linked to the initiation and progression of various tumors and their therapeutic strategies. However, the precise role of ER stress in uterine corpus endometrial cancer (UCEC) remains unclear.
METHODS
Data on patients with UCEC and control subjects were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA), we identified pivotal differentially expressed ER stress-related genes (DEERGs). Further validation of the significance of these genes in UCEC was achieved through consensus clustering and bioinformatic analyses. Using Cox regression analysis and several machine learning algorithms (least absolute shrinkage and selection operator [LASSO], eXtreme Gradient Boosting [XGBoost], support vector machine recursive feature elimination [SVM-RFE], and Random Forest), hub DEERGs associated with patient prognosis were effectively identified. Based on the four identified hub genes, a prognostic model and nomogram were constructed. Additionally, a drug sensitivity analysis and validation experiments were performed.
RESULTS
A total of 94 DEERGs were identified in patients with UCEC and healthy controls. Consensus clustering analysis revealed significant differences in prognosis, typical immune checkpoints, and tumor microenvironments between the subtypes. Using Cox regression analysis and machine learning, four hub DEERGs, MYBL2, RADX, RUSC2, and CYP46A1, were identified to construct a prognostic model. The reliability of the model was validated using receiver operating characteristic (ROC) curves. Decision curve analysis (DCA) demonstrated the superior predictive ability of the nomogram in terms of 3- and 5-year survival, compared with that of other clinical indicators. Drug sensitivity analysis revealed increased sensitivity to dactinomycin, docetaxel, selumetinib, and trametinib in the low-risk group. The expressions of RADX, RUSC2, and CYP46A1 were downregulated, whereas that of MYBL2 was upregulated in UCEC tissues, as demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence assays.
CONCLUSION
This study developed a stable and accurate prognostic model based on multiple bioinformatics analyses, which can be used to assess the prognosis of UCEC. This model may contribute to future research on the risk stratification of patients with UCEC and the formulation of novel treatment strategies.
PubMed: 38725627
DOI: 10.3389/fonc.2024.1362891 -
European Journal of Cancer (Oxford,... Sep 2022Regional lymph node disease (N1) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the...
Therapy and prognostic significance of regional lymph node involvement in embryonal rhabdomyosarcoma: a report from the European paediatric Soft tissue sarcoma Study Group.
PURPOSE
Regional lymph node disease (N1) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of nodal disease to the prognosis of patients with non-metastatic embryonal RMS (ERMS) and analyse their outcome by treatment received.
PATIENTS AND METHODS
Between 2005 and 2016, 1294 children with ERMS were enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol, 143 patients with N1. Treatment comprised 9 cycles of ifosfamide, vincristine and dactinomycin. Some patients also received doxorubicin and/or maintenance if enrolled in the randomised studies. Local treatment was planned after 4 cycles of chemotherapy and included surgery to remove macroscopic residual tumour and/or radiotherapy (primary tumour and involved nodes).
RESULTS
N1 patients were older and presented with tumours of unfavourable size, invasiveness, site and resectability. Unlike alveolar RMS, nodal involvement was more frequent in the head and neck area and rare in extremity sites. The 5-year event-free and overall survival were 75.5% and 86.3% for patients with N0, and 65.2% and 70.7% for patients with N1, respectively. The nodal involvement and the result of surgery at diagnosis (Intergroup Rhabdomyosarcoma Study group) were independent prognostic factors on multivariate analysis. Considering only patients with N1 ERMS, we were not able to identify any treatment variables which correlated with the outcome.
CONCLUSION
In the case of nodal involvement, patients with ERMS present different characteristics and a better outcome than alveolar RMS. Regional nodal involvement is an independent prognostic factor in ERMS, therefore it is appropriate to include this population in the high-risk category.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Disease-Free Survival; Humans; Infant; Lymph Nodes; Prognosis; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal
PubMed: 35763871
DOI: 10.1016/j.ejca.2022.05.033 -
European Journal of Haematology Sep 2020Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of...
OBJECTIVES
Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML.
METHODS
From September 2015 to February 2019, 26 adult patients with NPM1-mutated AML received dactinomycin in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n = 16, 62%), molecular relapses (n = 4, 16%), refractory disease (n = 1, 13%), or postremission therapy in second complete response (n = 1, 13%).
RESULTS
Median age was 62.5 years. Median number of dactinomycin cycle was 1 (1-8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. Grade 3-4 adverse events were thrombocytopenia (n = 11, 42%), neutropenia (n = 11, 42%), GI toxicity (n = 6, 23%), mucositis (n = 5, 19%), lung infection (n = 5, 19%), and skin rash (n = 2, 7.6%).
CONCLUSIONS
Dactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.
Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Biomarkers, Tumor; Dactinomycin; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Nuclear Proteins; Nucleophosmin; Prognosis; Recurrence; Remission Induction; Retreatment; Retrospective Studies; Treatment Outcome; Young Adult
PubMed: 32452083
DOI: 10.1111/ejh.13438 -
Transfusion Aug 2022Ewing sarcoma is one of the most frequent soft-tissue tumors in pediatric patients. The current treatment protocols recommend stem cell apheresis (SCA) after completion...
BACKGROUND
Ewing sarcoma is one of the most frequent soft-tissue tumors in pediatric patients. The current treatment protocols recommend stem cell apheresis (SCA) after completion of the second course of induction therapy with vincristine, ifosfamide, doxorubicine, and etoposide (VIDE). The feasibility of SCA and graft compositions in adult patients with Ewing sarcoma have not been previously analyzed.
METHODS AND MATERIALS
The authors analyzed 29 stem cell collections of 19 adult patients (9 male, 10 female) at a median age of 27 (range 19-53) years mobilized after VIDE (n = 17), cyclophosphamide/topotecan (n = 1) or vincristine, dactinomycin and ifosfamide (n = 1) chemotherapy. All patients were mobilized with filgrastim 5 μg/kg twice daily from day +7 of chemotherapy. The collections were performed if CD34+ cell count in peripheral blood was >10/μL. The target yields were ≥4×10 CD34+ cells/kg body weight.
RESULTS
Median CD34+ cells/μL in peripheral blood before SCA were 45.8 (range 6.7-614.4)/μL. The median cumulative yields were 10.6 (range 1.5-38.8) CD34+ cells/kg body weight and ≥2×10 in all but two patients (89%). CD34, CD3, and CD56 yields in collections after the third VIDE and after later courses did not differ. Four patients underwent high-dose therapy with autologous transplantation, and all were engrafted.
DISCUSSION
Stem cell mobilization is feasible in most Ewing sarcoma patients. Additionally, the present study's data suggest that it is safe to postpone stem cell collection to a later VIDE chemotherapy cycle if medically indicated.
Topics: Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Child; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Male; Middle Aged; Sarcoma, Ewing; Stem Cells; Vincristine; Young Adult
PubMed: 35801531
DOI: 10.1111/trf.17013