Clinical features and treatment outcomes of dedifferentiated and grade 3 chondrosarcoma: A multi-institutional study.
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ABSTRACT:
SUBMITTER: Kozawa E
PROVIDER: S-EPMC9277248 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Dedifferentiated chondrosarcoma (DC) is an extremely uncommon malignant bone tumor with dismal survival outcomes. The purpose of this study was to investigate whether the preoperative neutrophil/lymphocyte ratio (NLR) has the ability to predict overall survival (OS) in DC patients. Materials and Methods:Twenty-three DC patients with surgical resection were retrospectively reviewed between 2008 and 2015. The clinical pathological information and survival data were collected for analysis. The cut-off point for NLR was defined by receiver operating curve (ROC). The impact of NLR level on OS between two groups was compared using Kaplan-Meier curves with the Log-rank test. The association between NLR and OS was calculated by univariate and multivariate Cox proportional models. Results:From the ROC analysis, the optimal NLR cut-off point was 3.11. Patients with high NLR had a worse OS than low NLR (p = 0.003, Log-rank test). In univariate analysis, a significant association was observed between high NLR and poor OS (Hazard ratio (HR) 4.62, 95% confidence interval (CI) 1.48-14.34, p = 0.008). After adjustment of co-variables, high NLR had more than 4 times the risk of mortality (HR 4.01, 95% CI 1.12-14.26, p = 0.032). Conclusion:Preoperative NLR in peripheral blood is an easily accessible and cost-effective prognostic biomarker in DC patients. A prospective study with large sample size is warranted.
| S-EPMC7425651 | biostudies-literature
Project description:BackgroundDedifferentiated chondrosarcoma is a rare, highly malignant tumor with a poor survival. There are many confusing issues concerning the imaging feature that can facilitate early diagnosis and the factors that might be related to outcomes.MethodsTwenty-three patients with dedifferentiated chondrosarcoma confirmed by pathology were retrospectively reviewed from 2008 to 2015. The patients' clinical information, images from radiographs (n = 17), CT (n = 19), and MRI (n = 17), histological features, treatment and prognosis were analyzed.ResultsThere were 12 males and 11 females, and the mean age was 50.39 years old. Fourteen cases affected the axial bone (pelvis, spine), and 9 cases involved the appendicular bone. Seven (41.17%), 9 (47.36), and 12 (66.66%) lesions showed a biphasic nature on radiograph, CT and MRI, respectively. Of the lesions, 17.39% (4/23) were accompanied by pathological fractures. Histologically, the cartilage component was considered histological Grade1 in 12 patients and Grade 2 in 11 patients. The dedifferentiated component showed features of osteosarcoma in 8 cases, malignant fibrous histiocytoma in3 cases, myofibroblastic sarcoma in 1 case and spindle cell sarcoma in 11cases. Twenty-two cases were treated with surgical resection, and 17 cases achieved adequate (wide or radical) surgical margin. In 8 cases, surgery was combined with adjuvant chemotherapy. The overall median survival time was nine months; 17.4% of patients survived to five years.ConclusionAxial bone location, lung metastasis at diagnosis, inadequate surgical margin, incorrect diagnosis before surgery and pathological fractures was related to poorer outcome. Pre- or postoperative chemotherapy had no definitively effect on improved survival.
| S-EPMC5354284 | biostudies-literature
Project description:BACKGROUND:Chondrosarcoma is a heterogeneous group of primary bone sarcoma with an excellent overall survival after local therapy. However, the small percentage of patients who have no surgical treatment options have a very poor prognosis. We retrospectively collected data from these patients in four sarcoma centers and compared the progression-free survival (PFS) for the different treatment regimens used for the four chondrosarcoma subtypes. MATERIALS AND METHODS:Patients diagnosed with unresectable chondrosarcoma in all four major sarcoma centers were included, and data on first-line systemic therapy were retrospectively collected for analysis. RESULTS:A total of 112 patients were enrolled in this retrospective analysis: 50 conventional, 25 mesenchymal, 34 dedifferentiated, and 3 clear cell chondrosarcoma patients. In conventional chondrosarcoma patients, the longest mean PFS (6.7 months) was found in the group treated with antihormonal therapy. Patients diagnosed with mesenchymal chondrosarcoma were all treated with multidrug chemotherapy, and the mean PFS was 6.7 months. Doxorubicin monotherapy seems to have an unexplained better PFS than doxorubicin-based combination therapy in patients with dedifferentiated chondrosarcoma (5.5 vs. 2.8 months, respectively; p = .275). CONCLUSION:Prospective studies need to be conducted based on preclinical work to develop a uniform regimen to treat advanced chondrosarcoma patients according to the diagnosed subtype and improve survival. IMPLICATIONS FOR PRACTICE:Currently, there are no uniform treatment lines for advanced chondrosarcoma patients, which results in a very diverse group of treatment regimens being used. In this study, the data of 112 patients was collected. It was concluded that some treatment regimens seem to have a better progression-free survival compared with others, and that these results also differ between the chondrosarcoma subtypes. Prospective studies need to be conducted based on preclinical work to develop a uniform regimen to treat advanced chondrosarcoma patients according to the diagnosed histological subtype to improve their survival.
| S-EPMC6324625 | biostudies-literature
Project description:BackgroundPre-clinical studies have shown that metformin reduces intratumoral hypoxia, improves T-cell function, and increases sensitivity to PD-1 blockade, and metformin exposure has been associated with improved clinical outcomes in various types of cancer. However, the impact of this drug in diabetic melanoma patients has not yet been fully elucidated.MethodsWe reviewed 4,790 diabetic patients with stage I-IV cutaneous melanoma treated at the UPMC-Hillman Cancer Center and Memorial Sloan Kettering Cancer Center between 1996-2020. The primary endpoints included recurrence rates, progression free survival (PFS), and overall survival (OS) with and without metformin exposure. Tabulated variables included BRAF mutational status, immunotherapy (IMT) by type, and incidence of brain metastases.ResultsThe five-year incidence of recurrence in stage I/II patients was significantly reduced with metformin exposure (32.3% vs 47.7%, p=0.012). The five-year recurrence rate for stage III patients was also significantly reduced (58.3% vs 77.3%, p=0.013) in the metformin cohort. OS was numerically increased in nearly all stages exposed to metformin, though this did not reach statistical significance. The incidence of brain metastases was significantly lower in the metformin cohort (8.9% vs 14.6%, p=0.039).ConclusionThis is the first study to demonstrate significantly improved clinical outcomes in diabetic melanoma patients exposed to metformin. Overall, these results provide further rationale for ongoing clinical trials studying the potential augmentation of checkpoint blockade with metformin in advanced melanoma.
| S-EPMC10312386 | biostudies-literature
Project description:Chondrosarcomas are among the most malignant skeletal tumors. Dedifferentiated chondrosarcoma is a highly aggressive subtype of chondrosarcoma, with lung metastases developing within a few months of diagnosis in 90% of patients. In this paper we performed comparative analyses of the transcriptomes of five individual metastatic lung lesions that were surgically resected from a patient with dedifferentiated chondrosarcoma. We document for the first time a high heterogeneity of gene expression profiles among the individual lung metastases. Moreover, we reveal a signature of "multifunctional" genes that are expressed in all metastatic lung lesions. Also, for the first time, we document the occurrence of massive macrophage infiltration in dedifferentiated chondrosarcoma lung metastases.
| S-EPMC3289931 | biostudies-literature
Project description:Large patient cohorts are necessary to validate the efficacy of transoral robotic surgery (TORS) in the management of head and neck cancer.To review oncologic outcomes of TORS from a large multi-institutional collaboration and to identify predictors of disease recurrence and disease-specific mortality.A retrospective review of records from 410 patients undergoing TORS for laryngeal and pharyngeal cancers from January 1, 2007, through December 31, 2012, was performed. Pertinent data were obtained from 11 participating medical institutions.Select patients received radiation therapy and/or chemotherapy before or after TORS.Locoregional control, disease-specific survival, and overall survival were calculated. We used Kaplan-Meier survival analysis with log-rank testing to evaluate individual variable association with these outcomes, followed by multivariate analysis with Cox proportional hazards regression modeling to identify independent predictors.Of the 410 patients treated with TORS in this study, 364 (88.8%) had oropharyngeal cancer. Of these 364 patients, information about post-operative adjuvant therapy was known about 338: 106 (31.3) received radiation therapy alone, and 72 (21.3%) received radiation therapy with concurrent chemotherapy. Neck dissection was performed in 323 patients (78.8%). Mean follow-up time was 20 months. Local, regional, and distant recurrence occurred in 18 (4.4%), 15 (3.7%), and 10 (2.4%) of 410 patients, respectively. Seventeen (4.1%) died of disease, and 13 (3.2%) died of other causes. The 2-year locoregional control rate was 91.8% (95% CI, 87.6%-94.7%), disease-specific survival 94.5% (95% CI, 90.6%-96.8%), and overall survival 91% (95% CI, 86.5%-94.0%). Multivariate analysis identified improved survival among women (P = .05) and for patients with tumors arising in tonsil (P = .01). Smoking was associated with worse overall all-cause mortality (P = .01). Although advanced age and tobacco use were associated with locoregional recurrence and disease-specific survival, they, as well as tumor stage and other adverse histopathologic features, did not remain significant on multivariate analysis.This large, multi-institutional study supports the role of TORS within the multidisciplinary treatment paradigm for the treatment of head and neck cancer, especially for patients with oropharyngeal cancer. Favorable oncologic outcomes have been found across institutions. Ongoing comparative clinical trials funded by the National Cancer Institute will further evaluate the role of robotic surgery for patients with head and neck cancers.
| S-EPMC5019351 | biostudies-literature
Project description:BackgroundThe mitogen-activated protein kinases/extracelluar signal-regulated kinases pathway is involved in cell growth and proliferation, and mutations in BRAF have made it an oncogene of interest in pediatric cancer. Previous studies found that BRAF mutations as well as KIAA1549-BRAF fusions are common in intracranial low-grade gliomas (LGGs). Fewer studies have tested for the presence of these genetic changes in spinal LGGs. The aim of this study was to better understand the prevalence of BRAF and other genetic aberrations in spinal LGG.MethodsWe retrospectively analyzed 46 spinal gliomas from patients aged 1-25 years from Children's Hospital Colorado (CHCO) and The Hospital for Sick Children (SickKids). CHCO utilized a 67-gene panel that assessed BRAF and additionally screened for other possible genetic abnormalities of interest. At SickKids, BRAF V600E was assessed by droplet digital polymerase chain reaction and immunohistochemistry. BRAF fusions were detected by fluorescence in situ hybridization, reverse transcription polymerase chain reaction, or NanoString platform. Data were correlated with clinical information.ResultsOf 31 samples with complete fusion analysis, 13 (42%) harbored KIAA1549-BRAF. All 13 (100%) patients with confirmed KIAA1549-BRAF survived the entirety of the study period (median [interquartile range] follow-up time: 47 months [27-85 months]) and 15 (83.3%) fusion-negative patients survived (follow-up time: 37.5 months [19.8-69.5 months]). Other mutations of interest were also identified in this patient cohort including BRAF V600E , PTPN11, H3F3A, TP53, FGFR1, and CDKN2A deletion.ConclusionKIAA1549-BRAF was seen in higher frequency than BRAF V600E or other genetic aberrations in pediatric spinal LGGs and experienced lower death rates compared to KIAA1549-BRAF negative patients, although this was not statistically significant.
| S-EPMC7542983 | biostudies-literature
Project description:Objectives The purposes of this study are to assess the effectiveness of CyberKnife® stereotactic radiosurgery (SRS) in providing both initial and sustained pain relief for patients with both forms of trigeminal neuralgia (TN), assess potential prognostic factors, and examine treatment-related toxicities. Methods The RSSearch(®) Patient Registry was screened for TN cases from July 2007 to June 2015. We evaluated initial pain relief achieved by examining changes in the Visual Analog Scale (VAS) scores following SRS. Prognostic factors relating to initial pain relief and the relationship between maximum dose (Dmax) and toxicity incidence were analyzed via univariate logistic regressions. We evaluated prognostic factors relating to sustained pain relief using the Kaplan-Meier method and log-rank analysis. Results Our analysis included 125 TN1 patients and 38 TN2 patients with initial VAS scores ? 3 treated at 16 community radiotherapy centers. Median Dmax for both cohorts was 75 Gy with a larger range for TN1 cases (67.42 Gy - 110.29 Gy) as compared to TN2 cases (70.00 Gy - 78.48 Gy). At initial follow-up, mean VAS scores after SRS were significantly lower for TN1 and TN2 patients (p < 0.0001). The vast majority of TN1 (87.2%) and TN2 (86.8%) patients experienced initial pain relief. Higher initial VAS scores (p = 0.015) were correlated with a greater likelihood of initial treatment success for TN1 patients. We did not identify any treatment or patient characteristics that had significant effects on initial pain relief for TN2 patients. Of the TN1 cohort, 28 of 125 patients reported follow-ups one year or greater after SRS. Twenty-three of 28 TN1 patients (82%) reported VAS scores of 1 or less at one-year follow-up, and eight of 11 patients (72%) had VAS scores of 1 or less at the two-year follow-up. No potential prognostic factors for long-term pain relief were significant. Roughly 18% and 11% of TN1 and TN2 patients, respectively, experienced acute toxicities (all RTOG Grade 1 or 2), with the most common being sensory neuropathy, generalized pain, and nausea. Dmax > 75 Gy was not a predictor of toxicity incidence in TN1 cases (p = 0.597) but was significant for TN2 patients (p = 0.0009 following Fisher's exact test). Conclusions SRS is an effective treatment option for TN patients in community settings. Initial pain relief following SRS was achieved in a vast majority of TN patients with associated minor toxicities observed in less than 20% of all patients.
| S-EPMC4858443 | biostudies-literature
Project description:Purpose The prevalence and features of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) are not well characterized in the era of modern androgen receptor (AR)-targeting therapy. We sought to characterize the clinical and genomic features of t-SCNC in a multi-institutional prospective study. Methods Patients with progressive, metastatic castration-resistant prostate cancer (mCRPC) underwent metastatic tumor biopsy and were followed for survival. Metastatic biopsy specimens underwent independent, blinded pathology review along with RNA/DNA sequencing. Results A total of 202 consecutive patients were enrolled. One hundred forty-eight (73%) had prior disease progression on abiraterone and/or enzalutamide. The biopsy evaluable rate was 79%. The overall incidence of t-SCNC detection was 17%. AR amplification and protein expression were present in 67% and 75%, respectively, of t-SCNC biopsy specimens. t-SCNC was detected at similar proportions in bone, node, and visceral organ biopsy specimens. Genomic alterations in the DNA repair pathway were nearly mutually exclusive with t-SCNC differentiation ( P = .035). Detection of t-SCNC was associated with shortened overall survival among patients with prior AR-targeting therapy for mCRPC (hazard ratio, 2.02; 95% CI, 1.07 to 3.82). Unsupervised hierarchical clustering of the transcriptome identified a small-cell-like cluster that further enriched for adverse survival outcomes (hazard ratio, 3.00; 95% CI, 1.25 to 7.19). A t-SCNC transcriptional signature was developed and validated in multiple external data sets with > 90% accuracy. Multiple transcriptional regulators of t-SCNC were identified, including the pancreatic neuroendocrine marker PDX1. Conclusion t-SCNC is present in nearly one fifth of patients with mCRPC and is associated with shortened survival. The near-mutual exclusivity with DNA repair alterations suggests t-SCNC may be a distinct subset of mCRPC. Transcriptional profiling facilitates the identification of t-SCNC and novel therapeutic targets.
| S-EPMC6366813 | biostudies-literature
Project description:1) To measure the proportion of patients with chronic rhinosinusitis (CRS) who experience clinically significant improvement after endoscopic sinus surgery (ESS) in a prospective, multi-institutional fashion. 2) To identify preoperative characteristics that predict clinically significant improvement in quality of life (QOL) after ESS.Prospective, multi-institutional cohort study.Academic tertiary care centers.A total of 302 patients with CRS from three centers were enrolled between July 2004 and December 2008 and followed for an average of 17.4 months postoperatively. Preoperative patient characteristics, CT scan, endoscopy score, and pre- and postoperative quality of life (QOL) data were collected. Univariate and multivariate analyses were performed.Patients improved an average of 15.8 percent (18.9 points) on the Rhinosinusitis Disability Index and 21.2 percent (21.2 points) on the Chronic Sinusitis Survey (both P < 0.001). Patients significantly improved on all eight Medical Outcomes Study Short Form-36 (SF-36) subscales (all P < 0.001). Among patients with poor baseline QOL, 71.7 percent of patients experienced clinically significant improvement on the RSDI and 76.1 percent on the CSS. Patients undergoing primary surgery were 2.1 times more likely to improve on the RSDI (95% confidence interval [CI], 1.2, 3.4; P = 0.006) and 1.8 times more likely to improve on the CSS (95% CI, 1.1, 3.1; P = 0.020) compared with patients undergoing revision surgery.In this prospective, multi-institutional study, most patients experienced clinically significant improvement across multiple QOL outcomes after ESS. Specific patient characteristics provided prognostic value with regard to outcomes.
| S-EPMC2815335 | biostudies-literature