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In Vivo (Athens, Greece) 2023The prognosis of metastatic and inoperable sarcomas is extremely poor, and intensive chemotherapy-based treatment is typically administered to prolong survival....
BACKGROUND/AIM
The prognosis of metastatic and inoperable sarcomas is extremely poor, and intensive chemotherapy-based treatment is typically administered to prolong survival. Currently, pazopanib, eribulin, and trabectedin are key drugs used in patients with these sarcomas. The aim of the study was to identify prognostic factors for metastatic and inoperable bone and soft tissue sarcomas.
PATIENTS AND METHODS
Clinicopathological data of 46 patients with metastatic and inoperable sarcomas treated with pazopanib, eribulin, and trabectedin between January 2013 and February 2022 at our institution were retrospectively analyzed. Age, sex, primary tumor location, adverse effects, history of doxorubicin and radiation therapy, performance status scores, maximum tumor response, and survival duration were evaluated. The significant prognostic factors were identified using Cox proportional hazards models. Moreover, the 5-year survival rate was evaluated using the Kaplan-Meier method.
RESULTS
The median survival duration after treatment was 13.3 months, where the 5-year overall survival rate was estimated to be 9.85%. Both univariate and multivariate analyses revealed significant relationships among patient prognosis, performance status, and tumor response.
CONCLUSION
Performance status scores and tumor response were significantly associated with patient prognosis. Therefore, regardless of age, sex, primary tumor location, adverse effects, and history of doxorubicin and radiation therapy, use of cutting-edge drugs, such as pazopanib, eribulin, and trabectedin, may be advantageous in patients with advanced sarcomas, if their drug response and performance status scores are good.
Topics: Humans; Trabectedin; Prognosis; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Doxorubicin
PubMed: 37905627
DOI: 10.21873/invivo.13371 -
Cancer Medicine Nov 2023Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of...
BACKGROUND
Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib.
METHODS
We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance.
RESULTS
In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%).
CONCLUSION
We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.
Topics: Humans; Imatinib Mesylate; Sunitinib; Drug Monitoring; Pharmaceutical Preparations
PubMed: 37902257
DOI: 10.1002/cam4.6663 -
BMC Medical Genomics Oct 2023The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The...
OBJECTIVE
The impact of inflammatory response on tumor development and therapeutic response is of significant importance in clear cell renal cell carcinoma (ccRCC). The customization of specialized prognostication approaches and the exploration of supplementary treatment options hold critical clinical implications in relation to the inflammatory response.
METHODS
In the present study, unsupervised clustering was implemented on TCGA-KIRC tumors using transcriptome profiles of inflammatory response genes, which was then validated in two ccRCC datasets (E-MATB-1980 and ICGC) and two immunotherapy datasets (IMvigor210 and Liu et al.) via SubMap and NTP algorithms. Combining co-expression and LASSO analyses, inflammatory response-based scoring system was defined, which was evaluated in pan-cancer.
RESULTS
Three reproducible inflammatory response subtypes (named IR1, IR2 and IR3) were determined and independently verified, each exhibiting distinct molecular, clinical, and immunological characteristics. Among these subtypes, IR2 had the best OS outcomes, followed by IR3 and IR1. In terms of anti-angiogenic agents, sunitinib may be appropriate for IR1 patients, while axitinib and pazopanib may be suitable for IR2 patients, and sorafenib for IR3 patients. Additionally, IR1 patients might benefit from anti-CTLA4 therapy. A scoring system called IRscore was defined for individual ccRCC patients. Patients with high IRscore presented a lower response rate to anti-PD-L1 therapy and worse prognostic outcomes. Pan-cancer analysis demonstrated the immunological features and prognostic relevance of the IRscore.
CONCLUSION
Altogether, characterization of inflammatory response subtypes and IRscore provides a roadmap for patient risk stratification and personalized treatment decisions, not only in ccRCC, but also in pan-cancer.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Precision Medicine; Sorafenib; Axitinib; Prognosis
PubMed: 37885006
DOI: 10.1186/s12920-023-01687-5 -
Radiology Case Reports Dec 2023Malignant solitary fibrous tumors in the retroperitoneum are rare, and their treatment strategies have not yet been established. A 61-year-old woman with dyspnea...
Malignant solitary fibrous tumors in the retroperitoneum are rare, and their treatment strategies have not yet been established. A 61-year-old woman with dyspnea underwent laparotomy under a presumptive diagnosis of Meigs' syndrome. She underwent both adnexectomy and retroperitoneal tumor excision. The histologic diagnosis was of a fibrothecoma of both ovaries and a retroperitoneal solitary fibrous tumor that was considered malignant based on its mitotic activity. Local recurrence was observed 9 months postoperatively; re-excision was performed, and radiation therapy was administered. Four months later, metastasis to the left lung was detected, and a thoracoscopic resection was performed. Although pazopanib was administered subsequently, it was discontinued after 11 months because of proteinuria. She complained of dysphagia 3 weeks after the withdrawal of the drug, and a metastatic tumor was observed at the cranial base. Radiotherapy was initiated; however, she died of the disease 35 months after the primary surgery. Medical guidelines should be established for malignant solitary fibrous tumors to improve patient prognosis.
PubMed: 37868006
DOI: 10.1016/j.radcr.2023.09.073 -
Frontiers in Oncology 2023Soft tissue sarcomas harboring fusion are rare and challenging to treat. Pazopanib, a multi-tyrosine kinase inhibitor, is FDA-approved for advanced soft tissue...
Case report: The activity of multi-kinase VEGF inhibitor, Pazopanib, in metastatic undifferentiated round cell sarcomas harboring fusion: clinicopathological series of two cases and literature review.
Soft tissue sarcomas harboring fusion are rare and challenging to treat. Pazopanib, a multi-tyrosine kinase inhibitor, is FDA-approved for advanced soft tissue sarcomas, but predictive biomarkers for its efficacy remain unidentified. We conducted a study on > 240,000 neoplasms submitted to Caris Life Sciences (Phoenix, AZ) to detect rearrangements using whole transcriptome sequencing. Two sarcoma-experienced, board-certified pathologists performed histological reviews, and treatment/outcome information was collected. Among the identified cases ( = 18), we observed a diverse range of sarcoma and other cancers, including an intracranial myxoid mesenchymal tumor, mesothelioma, hyalinizing clear cell carcinomas of the head and neck, clear cell sarcomas, and undifferentiated round cell sarcomas, as well as histologically malignant tumors with epithelioid morphology. Notably, two undifferentiated, metastatic, abdominal round cell sarcoma cases treated with pazopanib demonstrated significant sustained partial response and clinical benefit. To explore the genetic factors associated with the efficacy of pazopanib in these cases, next-generation sequencing and fluorescence hybridization were analyzed for alterations in the tumors. The genomic analysis provided compelling evidence confirming the presence of fusion in both cases, with no other pathogenic gene variants or copy number alterations detected. These cases demonstrate the potential of Pazopanib as a promising therapeutic option for patients with fusion-positive soft tissue sarcomas, including metastatic undifferentiated round cell sarcomas. The sustained clinical benefit and partial responses observed in these cases warrant further research to validate these findings and explore the wider utility of Pazopanib in this rare and challenging subset of soft tissue sarcomas. Case studies: Case 1: A 49-year-old man presented with abdominal pain, weight loss, and chronic cough. A computed tomography (CT) of the chest, abdomen, and pelvis showed multiple lung nodules and masses and a right rectus mass that was biopsied and revealed an undifferentiated round cell sarcoma with a rare fusion . No additional pathogenic gene variants or copy number alterations were detected. He received neoadjuvant chemotherapy with three cycles of Vincristine, Adriamycin, and Ifosfamide (VAI) and seven cycles of Vincristine/Irinotecan and Temodar (VIT). After cycle 7 of VIT, he had surgical resection of the abdominal mass and received radiation for lung metastasis. He completed 13 cycles of VIT after which he presented with progression of disease and switched to monotherapy with Pazopanib. At the time of this analysis he had stable disease for 28 months. Case 2: A 75-year-old woman presented with pelvic pain and new onset constipation. CT abdomen showed a large pelvic mass and intraperitoneal tumor spread. Exploratory laparotomy revealed a ruptured pelvic mass and a small bowel tumor. Both tumors were proved to be high-grade, poorly differentiated sarcoma. Genomic analysis demonstrated an fusion but no other pathogenic gene variants or copy number alterations. She was treated initially for a primitive neuroectodermal tumor (PNET) with four cycles of Vincristine/Adriamycin/Cytoxan/Olaratumab but declined additional chemotherapy after progression. Two years later, she presented with recurrent abdominal mass and received one cycle of Temodar/Irinotecan, then she began Pozapanib and underwent palliative radiation to the entire pelvis. She has been on Pazopanib for 23 months with stable disease.
PubMed: 37829338
DOI: 10.3389/fonc.2023.1215003 -
Cureus Sep 2023Anticancer agents are responsible for a majority of adverse drug reactions (ADRs) in cancer patients. ADR reporting with anticancer drugs is very rare in India due to...
INTRODUCTION
Anticancer agents are responsible for a majority of adverse drug reactions (ADRs) in cancer patients. ADR reporting with anticancer drugs is very rare in India due to the lack of awareness and knowledge about the Pharmacovigilance Programme of India. Hence, this study was done to assess the pattern of ADRs with anticancer agents in cancer patients and to increase awareness about ADR monitoring among healthcare professionals.
MATERIALS AND METHODS
This is an observational, retrospective and non-interventional study conducted in an ADR monitoring centre (AMC) in Govt. Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, North India. Voluntarily reported ADR forms with anticancer drugs as suspected drugs over a period of seven years from January 2016 to December 2022 were analyzed. Various parameters were analyzed, which include demographic details of the patients, type of ADR, department reporting ADR and suspected drug. Causality assessment, severity assessment and preventability assessment were done according to the World Health Organization Uppsala Monitoring Centre (WHO-UMC) scale, modified Hartwig and Siegel scale and modified Schumock and Thornton scale, respectively.
RESULTS
The maximum numbers of ADRs were reported in the age group of 41-60 years (68.29%) and in females (59.75%). The maximum number of ADRs was reported with the use of taxanes (docetaxel and paclitaxel) (24.39%), targeted drugs (geftinib, imatinib, bortezomib, bevacizumab, rituximab and pazopanib) (24.39%) and platinum co-ordination complexes (cisplatin, oxaliplatin and carboplatin) (17.07%). Majority of the ADRs reported were shivering and ADRs on the skin. Majority of the ADRs were probable (64.70%), mild in nature (85.29%), definitely preventable (45.58%) and probably preventable (45.58%).
CONCLUSION
ADR monitoring is needed to increase the outcome of anticancer drug treatment in cancer patients. The quality of treatment in cancer patients can be improved through the timely management of these ADRs. It is a need of the present era to inform healthcare professionals about the Pharmacovigilance Programme to increase the reporting of ADRs due to anticancer drugs.
PubMed: 37822427
DOI: 10.7759/cureus.44984 -
The American Journal of Case Reports Oct 2023BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the...
Unusual Presentation of an Uncommon Malignancy: A 74-Year-Old Woman with Aggressive Fibromatosis of the Large Intestine Presenting as a Liver Mass and the Therapeutic Management.
BACKGROUND Desmoid tumors are a fibroblastic proliferation of soft tissues, with an extreme inclination for local dissemination and recurrence. Surgical excision is the usual treatment choice, with data regarding pharmaceutical treatment being scarce. CASE REPORT A 74-year-old female patient was admitted to "Laikon" General Hospital of Athens, Greece presenting with acute kidney injury secondary to diarrhea. The ultrasound, CT, and abdominal MRI performed showed a 12×6×10 cm tumorous liver lesion. Biopsy of the lesion revealed loosely organized, mesenchymal tissue with spindle cells, and myxoid stroma. Immunochemistry was positive for SMA and b-catenin. Right hemicolectomy was performed with tumor-free surgical margins (R0 resection) and tamoxifen was initiated. Six months after the last MRI (3 months after the use of tamoxifen), a follow-up MRI was performed. The tumor had increased to 14.2×11×12.3 cm, and at the next follow-up it had grown to 20.3×19 cm maximal dimensions; no new metastases were found. The patient received sorafenib and pazopanib. Our patient had PFS with sorafenib for more than 2 years and remained in a good performance status (ECOG 1). For Pazopanid, the median PFS for this treatment option was 6.5 months. CONCLUSIONS The results were good and show a promising method for the treatment of this rare but severe malignancy.
Topics: Female; Humans; Aged; Fibromatosis, Aggressive; Sorafenib; Tamoxifen; Liver Neoplasms
PubMed: 37812585
DOI: 10.12659/AJCR.939862 -
Scientific Reports Sep 2023Renal cell cancer is associated with the coagulation system. Long non-coding RNA (lncRNA) expression is closely associated with the development of clear cell renal cell...
Renal cell cancer is associated with the coagulation system. Long non-coding RNA (lncRNA) expression is closely associated with the development of clear cell renal cell carcinoma (ccRCC). The aim of this study was to build a novel lncRNA model to predict the prognosis and immunological state of ccRCC. The transcriptomic data and clinical data of ccRCC were retrieved from TCGA database, subsequently, the lasso regression and lambda spectra were used to filter prognostic lncRNAs. ROC curves and the C-index were used to confirm the predictive effectiveness of this model. We also explored the difference in immune infiltration, immune checkpoints, tumor mutation burden (TMB) and drug sensitivity between the high- and low-risk groups. We created an 8 lncRNA model for predicting the outcome of ccRCC. Multivariate Cox regression analysis showed that age, tumor grade, and risk score are independent prognostic factors for ccRCC patients. ROC curve and C-index revealed the model had a good performance in predicting prognosis of ccRCC. GO and KEGG analysis showed that coagulation related genes were related to immune response. In addition, high risk group had greater TMB level and higher immune checkpoints expression. Sorafenib, Imatinib, Pazopanib, and etoposide had higher half maximal inhibitory concentration (IC in the high risk group whereas Sunitinib and Bosutinib had lower IC. This novel coagulation-related long noncoding RNAs model could predict the prognosis of patients with ccRCC, and coagulation-related lncRNA may be connected to the tumor microenvironment and gene mutation of ccRCC.
Topics: Humans; Carcinoma, Renal Cell; RNA, Long Noncoding; Carcinoma; Kidney Neoplasms; Prognosis; Tumor Microenvironment
PubMed: 37770494
DOI: 10.1038/s41598-023-43065-2 -
Radiology Case Reports Nov 2023We present the case of a 75-year-old female in which a pulmonary tumor embolism was detected incidentally on a prostate-specific membrane antigen positron emission...
We present the case of a 75-year-old female in which a pulmonary tumor embolism was detected incidentally on a prostate-specific membrane antigen positron emission tomography-computed tomography restaging scan. This occurred on the background of renal cell carcinoma in remission with pazopanib systemic therapy and a right nephrectomy 4 years prior. An avidity to prostate-specific membrane antigen in the superior lingula of the left upper lobe of the lung coupled with contrast-enhanced computed tomography findings found the lesion to be a tumor thrombus. This case serves to highlight the effectiveness of incorporating contrast-enhanced computed tomography with prostate-specific membrane antigen positron emission tomography and to consider the rare diagnosis of a pulmonary tumor embolism.
PubMed: 37745764
DOI: 10.1016/j.radcr.2023.08.090 -
Frontiers in Pharmacology 2023Lung adenocarcinoma is a common cause of mortality in patients with cancer. Recent studies have indicated that copper-related cell death may not occur in the same way...
Lung adenocarcinoma is a common cause of mortality in patients with cancer. Recent studies have indicated that copper-related cell death may not occur in the same way as previously described. Long non-coding RNAs (lncRNAs) play a key role in the occurrence and development of tumors; however, the relationship between cuproptosis and lncRNAs in tumorigenesis and lung adenocarcinoma (LUAD) treatment has not been well established. Our study aimed to construct a model to analyze the prognosis of lung adenocarcinoma in patients using a carcinogenesis-related lncRNA (CR) signature. The transcriptional profiles of 507 samples from The Cancer Genome Atlas were assessed. Cox regression and co-expression analyses, and the least absolute shrinkage and selection operator (LASSO) were used to filter the CR and develop the model. The expression status of the six prognostic CRs was used to classify all samples into high- and low-risk groups. The overall disease-free survival rate was compared between the two groups. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to identify the pathways and mechanisms involved in this model. Subsequently, immunotherapy response, sensitivity, and correlation analyses for several anti-tumor medications were performed. experiments, including qPCR, were conducted in nine lung adenocarcinoma cell lines and 16 pairs of lung adenocarcinoma and para-carcinoma tissues. After confirmation using the ROC curve, patients in the low-risk category benefited from both overall and disease-free survival. Gene Ontology analysis highlighted cell movement in the model. In the experiments, qPCR results showed the expression levels of six CRs in 16 pairs of carcinoma and para-carcinoma tissues, which were in accordance with the results of the model. AL138778.1 is a protective factor that can weaken the invasion and migration of A549 cells, and AL360270.1 is a hazardous factor that promotes the invasion and migration of A549 cells. According to this model, targeted treatments such as axitinib, gefitinib, linsitinib, pazopanib, and sorafenib may be more appropriate for low-risk patients. Six CR profiles (AL360270.1, AL138778.1, CDKN2A-DT, AP003778.1, LINC02718, and AC034102.8) with predictive values may be used to evaluate the prognosis of patients with lung adenocarcinoma undergoing therapy.
PubMed: 37745054
DOI: 10.3389/fphar.2023.1236655