The implicated clinical factors for outcomes in 304 patients with salivary duct carcinoma: Multi-institutional retrospective analysis in Japan.
Ontology highlight
ABSTRACT: Background
Salivary duct carcinoma (SDC) is a high-grade salivary malignancy that frequently occurs as the carcinomatous component of carcinoma ex pleomorphic adenoma. We herein examined the clinical factors affecting outcomes in a large cohort of SDC.Methods
We selected 304 SDC cases and investigated clinical characteristics and the factors affecting outcomes.Results
The median age of the cases examined was 68 years, the most common primary site was the parotid gland (238 cases), and there was a male predominance (M/F = 5:1). Outcomes were significantly worse when the primary tumor site was the minor salivary glands (SG) than when it was the major SG. Outcomes were also significantly worse in pN(+) cases (161 cases) than in pN0 cases, particularly those with a metastatic lymph node number ≥11. The cumulative incidence of relapse and distant metastases was significantly higher in stage IV cases than in stage 0-III cases.Conclusions
The absolute number of lymph node metastases, higher stages, and the minor SG as the primary tumor site were identified as factors affecting the outcome of SDC.
SUBMITTER: Kusafuka K
PROVIDER: S-EPMC9311811 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional retrospective cohort study of 140 SDC patients. The survival impact of these hematological markers was evaluated using multivariate proportional hazard models.High mGPS (≥1) was significantly associated with worse survival (3-year overall survival (OS): 16.7% vs 66.1%, p-value=0.003; 3-year progression-free survival (PFS): 0.0% vs 27.9%, p-value<0.001). Additionally, high C-reactive protein (CRP) (≥0.39 mg/dl) was significantly associated with worse survival (3-year OS: 32.1% vs 68.2%, p-value=0.001; 3-year PFS: 7.1% vs 31.1%, p-value<0.001). These associations were consistent with multivariate analysis adjusted for established prognostic factors. Although we also found significant association of high NLR (≥2.5) with OS (HR 1.80; 95% confidence interval, 1.05-3.08) in multivariate analysis, this association were inconsistent with the results of PFS. In addition, we found no significant associations of PLR with survival. In conclusion, we found that mGPS, CRP and NLR were identified as prognostic factors associated with survival in SDC patients.
| S-EPMC5352036 | biostudies-literature
Project description:BackgroundThe Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a risk-stratification reporting system that was introduced in 2018. The objective of this multi-institutional study was to evaluate the utility of the MSRSGC in Japan.MethodsIn total, 1608 fine-needle aspiration samples with matching histologic diagnoses were retrieved from 12 large institutions in Japan. The diagnostic categories of the MSRSGC were assigned prospectively or retrospectively, and the results were compared with the histologic diagnoses.ResultsThe cases were classified as follows: nondiagnostic, 18.1%; non-neoplastic, 4.1%; atypia of undetermined significance, 11.5%; neoplasm-benign, 43.7%; salivary gland neoplasm of uncertain malignant potential, 9.6%; suspicious for malignancy, 3.6%; and malignant, 9.4%. The risk of neoplasm and the risk of malignancy in each MSRSGC category were as follows: nondiagnostic, 72.9% and 13.4%, respectively; non-neoplastic, 15.2% and 9.1%, respectively; atypia of undetermined significance, 77.9% and 24.9%, respectively; neoplasm-benign, 99% and 1.8%, respectively; salivary gland neoplasm of uncertain malignant potential, 94.8% and 37%, respectively; suspicious for malignancy, 100% and 89.7%, respectively; and malignant, 100% and 99.3%, respectively. The accuracy of the MSRSGC for diagnosing neoplasms was 97.8%, and its accuracy for diagnosing malignancy was 97.3%. Institutions that used Romanowsky-stained preparations had lower nondiagnostic rates and lower risks of neoplasm and malignancy in the non-neoplastic category.ConclusionsThe MSRSGC is useful for risk stratification and quality control. Widespread use of the MSRSGC would improve the accuracy of salivary gland cytology and lead to better patient care in Japan.
| S-EPMC9290724 | biostudies-literature
Project description:Salivary duct carcinoma is a rare and aggressive salivary gland cancer subtype with poor prognosis. Its mutational landscape has been described rather exhaustively but little is known regarding its functional genomics and tumor microenvironment. In this study, we combined transcriptomics and proteomics to obtain a first characterization of deregulated pathways, which revealed the importance of Notch, TGB-β, and interferon-γ signaling. We then associated computational biology, immunohistochemistry, multiplexed immunofluorescence, and digital imaging to start charting the cellular network within the microenvironment, identify two well-defined groups of tumors according to their immune infiltrate, find novel SDC immune checkpoints, and show the role macrophages and NK cells in immunosuppression. Furthermore, we showed a clear trend between recurrence free survival and M2 macrophage abundance, and, independently, α-SMA abundance – a measure of desmoplastic stromal reaction. Altogether, these many findings open new perspectives for SDC. Classical patient stratification according to the immune infiltrate should be applied before choosing an immunotherapy. The microenvironment offers new actionable targets such as macrophages or NK cells, or even fibroblasts or hyaluronic acid in the absence of immune infiltrate. Related therapies are developed e.g. against pancreatic tumors that could inspire equivalents for SDC. Combinations with drugs targeting SDC mutated genes might also contribute to patient-specific regimens.
2020-05-26 | PXD015885 | Pride
Project description:Salivary duct carcinoma (SDC) is one of the most aggressive subtypes of salivary gland cancers. Conventional chemotherapy and/or radiation have shown only limited clinical efficacy in the treatment of recurrent or metastatic SDC. Currently, clinically approved targeted-therapeutics are not generally applicable except in very limited cases, and there exists a strong need for the development of treatment against this unique tumor type. To further interrogate genomic features of SDC, we have conducted multi-omic profiling of the SDC to describe the genomic alterations prevalent in this disease. Whole-genome sequencing, whole exome-sequencing and transcriptome sequencing were performed on a discovery cohort of 10 SDC samples. Targeted genomic profiling was performed in additional 32 SDC samples to support the findings obtained from the original discovery cohort. The cancer cohort was characterized by an average mutation burden of 85 somatic exonic mutations per tumor sample. The cohort harbored a mutational signature of BRCA and APOBEC/AID. Several genes, including TP53, RB1, SMAD4, HRAS, APC, PIK3CA and GNAQ were recurrently somatically altered in SDC. A novel fusion gene, generated by genomic rearrangement, MYB-NHSL1, was also noted. Our findings represent a significant layer in the systematic understanding of potentially clinically useful genomic and molecular targets for a subset of recurrent/metastatic SDC.
| S-EPMC7490354 | biostudies-literature
Project description:PurposeThis series reports long-term clinical outcomes of patients with salivary duct carcinoma (SDC), which is associated with a poor prognosis.Methods and materialsEighty-nine patients with SDC were treated with curative intent from February 5, 1971, through September 15, 2018. Kaplan-Meier and competing risk analyses were used to estimate locoregional control, distant metastasis-free survival (DMFS), progression-free survival, and overall survival (OS). Cox regression analyses of disease and treatment characteristics were performed to discover predictors of locoregional control, DMFS, and OS.ResultsMedian follow-up was 44.1 months (range, 0.23-356.67). The median age at diagnosis was 66 years (interquartile range, 57-75). Curative surgery followed by adjuvant radiation therapy was performed in 73 patients (82%). Chemotherapy was delivered in 26 patients (29.2%). The 5-year local recurrence and distant metastasis rates were 27% and 44%, respectively, with death as a competing risk. Distant metastasis was associated with lymph node-positive disease (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.38-7.23; P = .006), stage IV disease (HR, 4.78; 95% CI, 1.14-20.11; P = .033), perineural invasion (HR, 4.56; 95% CI, 1.74-11.97; P = .002), and positive margins (HR, 9.06; 95% CI, 3.88-21.14; P < .001). Median OS was 4.84 years (95% CI, 3.54-7.02). The 5-year OS was 42%. Reduced OS was associated with lymphovascular space invasion (HR, 3.49; 95% CI, 1.2-10.1; P = .022), perineural invasion (HR, 2.05; 95% CI, 1.06-3.97; P = .033), positive margins (HR, 2.7; 95% CI, 1.3-5.6; P = .011), N2 disease (HR, 1.88; 95% CI, 1.03-3.43; P = .04), and N3 disease (HR, 11.76; 95% CI, 3.19-43.3; P < .001).ConclusionsIn this single-institution, multicenter retrospective study, the 5-year survival was 42% in patients with SDC. Lymphovascular space invasion, lymph node involvement, and higher staging at diagnosis were associated with lower DMFS and OS.
| S-EPMC10157113 | biostudies-literature
Project description:To determine the characteristics of 90-day morbidity and mortality after radical cystectomy in Japanese octogenarians.A retrospective multi-institutional study. We reviewed the records of 834 patients treated by open radical cystectomy between 1997 and 2010. All complications within 90 days after surgery were sorted into the 11 categories proposed by the Memorial Sloan-Kettering Cancer Center and graded according to the modified Clavien-Dindo system. We compared the characteristics of complications between ?80-year (n = 86) and <80-year (n = 748) groups. Multivariate regression models were used to determine the predictors of complications.American Society of Anesthesiologists score III-IV was more frequent (14% vs. 6%, respectively, P < 0.0001), and ureterocutaneostomy was more frequently performed (30% vs. 21%, respectively, P = 0.0148) in the ?80-year group compared with <80-year group. There were no significant differences in the rates of any complication, major (Grade 3-5) complication, or 90-day mortality between the two groups (?80-year group: 70%, 21%, 3.5%, respectively, <80-year group: 68%, 22%, 2%, respectively). The ?80-year group had fewer genitourinary complications (7% vs. 16%, respectively, P = 0.0131). Multivariate regression analyses revealed that bowel-using urinary diversion (P = 0.0031) and the operative time (P = 0.0269) were significant predictors of any grade of complications, and a male sex (P = 0.0167), annual cystectomy volume (P = 0.0284) and prior cardiovascular comorbidity (P = 0.0034) were significant predictors of major complications.In our experience, radical cystectomy in Japanese octogenarians caused similar perioperative comorbidities. Old age as a single criterion should not be used to abandon radical cystectomy; careful preoperative assessment is mandatory.
| S-EPMC5896694 | biostudies-other
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:Background: No studies evaluating the clinical outcomes of radiotherapy (RT) for hepatocellular carcinoma (HCC) in the caudate lobe have been available to date. The purpose of this study was to evaluate the effectiveness and safety of RT for HCC in the caudate lobe. Material and Methods: Seventy patients with HCC in the caudate lobe treated with RT from a multi-institutional database were included in this study. The median equivalent dose in 2 Gy (EQD2) was 80.0 Gy10 (range, 31.3-99.3), and freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were evaluated. Results: The median time of follow-up was 47.9 months (range, 3.4-127), and the 5-year FFLP, PFS, and OS rates were 80.6% [95% confidence interval (CI), 70.8-91.8], 13.8% (95% CI, 7.5-25.4), and 51.3% (95% CI, 39.9-66.1), respectively. In the multivariate analysis, the radiation dose was significantly associated with the FFLP rate [hazard ratio (HR), 0.57 per 10 Gy10 increase, p = 0.001], and the status of FFLP was significantly associated with OS (HR, 2.694, p = 0.014). The overall rate of ≥grade 3 adverse events was 5.7% (4 of 70), and RT-related mortality was not observed. Conclusion: RT for HCC in the caudate lobe showed promising FFLP and OS rates with safe toxicity profiles. These findings suggest that RT may be a promising treatment option for HCC in the caudate lobe.
| S-EPMC7952981 | biostudies-literature
Project description:Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.
| S-EPMC5662845 | biostudies-other
Project description:Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: "HER2-positive" (HER2+/any AR), "Luminal-AR" (HER2-/AR+), and "Basal-like" (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher's test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.
| S-EPMC7937931 | biostudies-literature