scholarly journals Benefit of Postoperative Radiotherapy for Patients With Nonmetastatic Adrenocortical Carcinoma: A Population-Based Analysis

2021 ◽  
Vol 19 (12) ◽  
pp. 1425-1432
Author(s):  
Kan Wu ◽  
Xu Liu ◽  
Zhihong Liu ◽  
Yiping Lu ◽  
Xianding Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Adrenocortical Carcinoma ◽  
Survival Benefit ◽  
Cox Regression ◽  
Radical Surgery ◽  
Postoperative Radiotherapy ◽  
Disease Stage ◽  
Cox Regression Analysis ◽  
Risk Of Recurrence ◽  
Risk Of Death

Background: Adrenocortical carcinoma (ACC) is an aggressive cancer with high recurrence rates and poor prognosis, even after radical surgery. The survival benefit of adjuvant radiotherapy (RT) in patients with ACC has not been well explored. The aim of this study was to evaluate the effect of adjuvant RT on the survival outcome of patients with ACC. Patients and Methods: All patients with nonmetastatic ACC who underwent complete resection were identified from the SEER database (2004–2016). Overall survival (OS) was estimated using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to identify prognostic factors associated with survival. Results: Of 365 patients with nonmetastatic ACC, 55 (15.1%) received adjuvant RT and the remainder underwent surgery alone. Patient characteristics were similar between the 2 groups, but those with a higher disease stage were more likely to receive adjuvant RT. Overall, patients receiving RT seemed to have better survival compared with the non-RT group (3-year OS rate, 63.1% vs 52.8%; P<.062). After adjustment for confounding factors, adjuvant RT was indeed associated with a 48% decreased risk of death (hazard ratio, 0.52; 95% CI, 0.29–0.91; P=.023) for all patients. In addition, adjuvant RT may confer a survival benefit only in patients with a high risk of recurrence (3-year OS rate, 55.1% vs 40.0%; P=.048) rather than in those with low/moderate-risk ACC (P=.559). Conclusions: Our findings suggest that adjuvant RT may be associated with improved survival in patients with nonmetastatic ACC who underwent radical surgery, especially those with high risk of recurrence.

scholarly journals Adrenocortical Carcinoma Treatment in the Netherlands: An Analysis From the Netherlands Cancer Registry From 2014 to 2019

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A76-A76
Author(s):  
Rebecca Steenaard ◽  
Marieke Rutjens ◽  
Harm Reinout Haak
Keyword(s):  
The Netherlands ◽  
Cancer Registry ◽  
Adrenocortical Carcinoma ◽  
Survival Benefit ◽  
Cox Regression ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Cox Regression Analysis ◽  
Netherlands Cancer Registry ◽  
Number Of Patients

Abstract Background: Adrenocortical carcinoma (ACC) is a rare disease with often poor prognosis. Previous research has shown that surgery in a Dutch Adrenal Network (DAN) center increases the chance of survival. We aim to explore the determinants and survival of patients with ACC recently treated in the Netherlands both within and outside DAN centers. Methods: We analyzed retrospectively collected data from 172 adult patients with newly diagnosed ACC and 97 patients with recurrence or new metastases, registered between 2014 and 2019 in the Netherlands Cancer Registry. Differences in survival were analyzed with cox-regression analysis. Results: More than half of the new cases presented with advance disease (25.7% stage III, 34.6% stage IV) and the median survival was 29 months. The majority of treatments occurred within a DAN center (87.2% of surgery, compared to 56.4% between 1999 and 2009; and 94.5% of medical treatment). There were no differences in patient characteristics between the centers apart from a relatively high number of patients with stage IV disease outside DAN centers (47.2% vs. 28.7%). Adrenal resection and mitotane therapy both resulted in a significant survival benefit (resection HR 0.29, CI95%[0.17–0.49]; mitotane HR 0.61, CI95%[0.37–0.99], corrected for stage). Still, a remarkable proportion of patients with advanced disease received no mitotane treatment (39.8%). Due to the small number of patients treated outside DAN centers, survival benefits could not be tested. Conclusions: Centralization of ACC care in the Netherlands has improved since the previous report, but a further improvement in centralization of surgery can be made. Adrenal resection and mitotane treatment remain the main form of treatment, with a clear survival benefit. Further research is necessary to determine why mitotane treatment is withheld in a large proportion of patients with advance disease.

scholarly journals Adjuvant mitotane therapy is beneficial in non-metastatic adrenocortical carcinoma at high risk of recurrence

2019 ◽  
Vol 180 (6) ◽  
pp. 387-396 ◽  
Author(s):  
A Calabrese ◽  
V Basile ◽  
S Puglisi ◽  
P Perotti ◽  
A Pia ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adrenocortical Carcinoma ◽  
Hormone Secretion ◽  
Treated Group ◽  
Stage Iii ◽  
Ki67 Index ◽  
Risk Of Recurrence ◽  
Risk Of Death ◽  
Predictors Of Response

Objective Many patients with adrenocortical carcinoma (ACC) suffer from tumor recurrence despite radical surgery. Evidence on the post-operative use of mitotane is controversial and no predictors of response are available. We aimed to assess whether adjuvant mitotane treatment may prolong survival in patients with non-metastatic ACC following complete resection and whether ACC patients at high risk of recurrence may benefit from treatment. Design and methods We retrospectively reviewed data from 152 non-metastatic ACC patients followed at the San Luigi Gonzaga Hospital: 100 patients were treated with adjuvant mitotane and 52 patients were left untreated following surgery. We assessed a number of potential predictive factors of recurrence and death. Mitotane effect was explored stratifying patients by staging (stage I–II vs stage III), hormone secretion (yes vs no) and Ki67 index. Results The non-treated group had a higher risk of recurrence (HR: 2.79, 95%CI: 1.58–4.91; P < 0.001) than mitotane-treated group, while overall survival was not significantly different between groups. Hormone secretion, elevated Weiss score and elevated Ki67 index confer a higher risk of both recurrence and death and stage III ACC of death. Adjuvant mitotane treatment reduced significantly the risk of death in patients with elevated Ki67 index (P = 0.005) and in patients with stage III ACC (P = 0.02). Conclusions Adjuvant mitotane may prolong recurrence-free survival in radically resected ACC patients with acceptable toxicity and may also prolong overall survival in a subgroup of ACC patients at high risk of recurrence.

scholarly journals Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Surgery for Adenocarcinomas of Parotid Gland: A Population-based Longitudinal Cohort Study

2020 ◽  
Author(s):  
Wenlong Qiu ◽  
Wenhao Zhang
Keyword(s):  
Cohort Study ◽  
Risk Stratification ◽  
Survival Benefit ◽  
Risk Model ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
Prognostic Score ◽  
Population Based ◽  
Comprehensive Treatment ◽  
Cox Regression Analysis

Abstract Background: Radiotherapy (RT) after surgery is a treatment option in the management of parotid adenocarcinoma, and the role of adjuvant RT for parotid adenocarcinoma remains to be clarified. The survival benefit of postoperative radiotherapy (PORT) based on prognostic risk factors needs further determination.Materials and methods: In this retrospective cohort study using SEER data, patients were divided into surgery+RT (RT group) and surgery alone (non-RT group). A prognostic risk model was constructed to stratify patients based on the survival rate. We performed a Cox regression analysis with propensity score weighting to evaluate survival benefit between the two groups. Results: We identified 2223 eligible patients with parotid adenocarcinoma, 1449 (65.2%) in the RT group and 774 (34.8%) in the non-RT group. Overall, 674 cancer-specific deaths occurred over a median follow-up of 141 months, the overall survival (OS) of RT group was better than that of non-RT group in the weighted analysis (HR=0.656, 95% CI=0.487-0.882, P=0.005). Significant survival improvements in the RT group compared with the non-RT group were only observed in patients with high risk (HR=0.647, 95% CI=0.426-0.983, P=0.041). The survival benefit of RT was significantly correlated with prognostic risk stratification (P<.001).Conclusion: In this population-based study, the patient prognostic risk stratification for parotid adenocarcinoma is associated with the magnitude of survival improvement by RT after surgery, suggesting that this risk model could provide decision guidance on comprehensive treatment strategy.

Trimodality approach, using modern radiation techniques, for management of locally advanced adrenocortical carcinoma – case report

2021 ◽  
pp. 1-4
Author(s):  
André Laranja ◽  
Carolina Ferreira
Keyword(s):  
Case Report ◽  
High Risk ◽  
Local Recurrence ◽  
Adrenocortical Carcinoma ◽  
Postoperative Radiotherapy ◽  
Locally Advanced ◽  
Volumetric Modulated Arc Therapy ◽  
Case Presentation ◽  
Risk Of Recurrence ◽  
Arc Therapy

Abstract Background: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Surgery is the mainstay of treatment, still even after a R0 surgical margins, there is a high risk of recurrence. Case Presentation: A 26-year-old female diagnosed with a large functioning ACC treated with a trimodality approach (surgery, radiotherapy and chemotherapy). Postoperative radiotherapy was proposed regarding the high risk of recurrence. A dose of 50.4 Gy in 28 fractions was delivered to the patient using a volumetric-modulated arc therapy plan. Radiotherapy was safe and well tolerated, and no local recurrence was observed so far (13 months after radiotherapy). Conclusions: Due to the rarity of ACC and the lack of evidence regarding this entity, therapeutic approach can be challenging. Recent evidence suggests that radiotherapy could have an important role in the therapeutic arsenal.

scholarly journals Liver-Metastasis-Related Genes are Potential Biomarkers for Predicting the Clinical Outcomes of Patients with Pancreatic Adenocarcinoma

2021 ◽  
Vol 27 ◽  
Author(s):  
Yinlei Dong ◽  
Junjie Tian ◽  
Bingqian Yan ◽  
Kun Lv ◽  
Ji Li ◽  
...  
Keyword(s):  
High Risk ◽  
Liver Metastasis ◽  
Clinical Outcomes ◽  
Pancreatic Adenocarcinoma ◽  
Primary Tumor ◽  
Cox Regression ◽  
Risk Scores ◽  
R0 Resection ◽  
Cox Regression Analysis ◽  
Risk Of Death

It is widely acknowledged that metastasis determines the prognosis of pancreatic adenocarcinoma (PAAD), and the liver is the most primary distant metastatic location of PAAD. It is worth exploring the value of liver-metastasis-related genetic prognostic signature (LM-PS) in predicting the clinical outcomes of PAAD patients post R0 resection. We collected 65 tumors and 165 normal pancreatic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression project (GTEx), respectively. Differentially expressed genes (DEGs) between primary tumor and normal pancreatic samples were intersected with DEGs between primary tumor samples with liver metastasis and those without new tumor events. The intersected 45 genes were input into univariate Cox regression analysis to identify the prognostic genes. Thirty-three prognostic liver-metastasis-related genes were identified and included in least absolute shrinkage and selection operator (LASSO) analysis to develop a seven-gene LM-PS, which included six risk genes (ANO1, FAM83A, GPR87, ITGB6, KLK10, and SERPINE1) and one protective gene (SMIM32). The PAAD patients were grouped into low- and high-risk groups based on the median value of risk scores. The LM-PS harbored an independent predictive ability to distinguish patients with a high-risk of death and liver metastasis after R0 resection. Moreover, a robust prognostic nomogram based on LM-PS, the number of positive lymph nodes, and histologic grade were established to predict the overall survival of PAAD patients. Besides, a transcription factor‐microRNA coregulatory network was constructed for the seven LM-PS genes, and the immune infiltration and genomic alterations were systematically explored in the TGCA-PAAD cohort.

66 Complex markers of survival from pembrolizumab: the potential predictive role of tumor mutational burden (TMB) and KRAS

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A71-A71
Author(s):  
Yong Hee Lee ◽  
Carrie Hoefer ◽  
Paul DePietro ◽  
Mary Nesline
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Cox Regression ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
High Status ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Mutational Status ◽  
Increased Risk

BackgroundPembrolizumab, with or without chemotherapy, is NCCN guideline-recommended treatment for NSCLC cancer patients depending on tumor PD-L1 status by IHC. PD-L1 IHC provides guidance for treatment selection for response, but does not accurately predict survival benefit from pembrolizumab. Emerging evidence suggests TMB and other genomic markers (KRAS, STK11, TP53 mutations), may have clinical utility for predicting survival benefit.MethodsWe identified a cohort of metastatic EGFR/ALK wild type NSCLC patients (n=116) whose tumors underwent comprehensive profiling (June 2017-March 2019) for genomic variants, TMB and PD-L1 IHC 22C3 prior to selection of pembrolizumab (n=43), pembrolizumab + chemotherapy (n=41), or chemotherapy only (excluding subsequent targeted therapy or immunotherapy) (n=32) at Roswell Park Comprehensive Cancer Center, with at least one year of follow up. TMB was assessed using a 1.75 Mb capture of 409 oncogenes with full exon coverage (DNA-Seq), with ‘high’ TMB interpreted as ≥10 mutations/Mb. Electronic pharmacy records were curated to create pre and post-test treatment histories for each patient. Cox regression analysis evaluated OS with pembrolizumab monotherapy or pembrolizumab + chemotherapy vs chemotherapy only, adjusting for covariates including oncogenic driver mutations, TMB, PD-L1 IHC demographics, clinicopathologic characteristics, prior treatment, and performance status. Using the same model, we then assessed overall survival for each treatment group by TMB, KRAS, STK11, and TP53 mutant status.ResultsOverall, 47% of tumors were PD-L1 high, 47% TMB high, 34% KRAS mutant (codons 12, 13, 60, 61), 52% TP53 mutant and 16% STK11 mutant. As expected, pembrolizumab with or without chemotherapy significantly improved overall survival (OS) compared to chemotherapy alone; with TMB, smoking, and ECOG status identified as significant covariates. PD-L1 IHC status was not associated with OS for any treatment. TMB high status was significant for OS benefit with pembrolizumab either as monotherapy [HR=0.02; CI=0.01–0.40; p=0.01] or in combination with chemotherapy [HR=0.20; CI=0.04–0.95; p=0.04]. KRAS mutant status was independently significant for OS benefit from pembrolizumab + chemotherapy [HR=0.01; CI=0.01–0.79; p=0.04] but not for pembrolizumab monotherapy or chemotherapy alone. Among patients who received pembrolizumab monotherapy, there was a trend toward increased risk of death in those with STK11 mutations [HR=17.54; CI=0.35–1,000; p=0.15], whereas TP53 mutant status trended toward survival benefit [HR=0.18; CI=0.02–1.53; p=0.11].ConclusionsData comparing pembrolizumab treatments with chemotherapy and independent marker associations suggest TMB has predictive power for determining overall survival benefit from pembrolizumab, while KRAS, STK11, and TP53 mutational status demonstrated potential prognostic relevance for NSCLC.

scholarly journals Atorvastatin is unlikely to prevent rheumatoid arthritis in high risk individuals: results from the prematurely stopped STAtins to Prevent Rheumatoid Arthritis (STAPRA) trial

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001591
Author(s):  
Laurette van Boheemen ◽  
Samina Turk ◽  
Marian van Beers-Tas ◽  
Wouter Bos ◽  
Diane Marsman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Cox Regression ◽  
Controlled Trial ◽  
Pharmacological Intervention ◽  
Trial Participation ◽  
Double Blind ◽  
Cox Regression Analysis ◽  
Atorvastatin Group ◽  
Clinical Arthritis

ObjectivesPersons at high risk of rheumatoid arthritis (RA) might benefit from a low-risk pharmacological intervention aimed at primary prevention. Previous studies demonstrated disease-modifying effects of statins in patients with RA as well as an association between statin use and a decreased risk of RA development. A randomised, double-blind, placebo-controlled trial investigated whether atorvastatin could prevent arthritis development in high-risk individuals.MethodsArthralgia patients with anticitrullinated protein antibody (ACPA) >3 xULN or ACPA and rheumatoid factor, without (a history of) arthritis, were randomised to receive atorvastatin 40 mg daily or placebo for 3 years. The calculated sample size was 220 participants. The primary endpoint was clinical arthritis. Cox regression analysis was used to determine the effect of atorvastatin on arthritis development.ResultsDue to a low inclusion rate, mainly because of an unwillingness to participate, the trial was prematurely stopped. Data of the 62 randomised individuals were analysed. Median follow-up was 14 (inner quartiles 6–35) months. Fifteen individuals (24%) developed arthritis: 9/31 (29%) in the atorvastatin group; 6/31 (19%) in the placebo group: HR 1.40, 95% CI 0.50 to 3.95.ConclusionsIn this small set of randomised high-risk individuals, we did not demonstrate a protective effect of atorvastatin on arthritis development. The main reason for the low inclusion was unwillingness to participate; this may also impede other RA prevention trials. Further research to investigate and solve barriers for prevention trial participation is needed.

scholarly journals Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

2021 ◽  
Vol 14 ◽  
pp. 175628482110234
Author(s):  
Mario Romero-Cristóbal ◽  
Ana Clemente-Sánchez ◽  
Patricia Piñeiro ◽  
Jamil Cedeño ◽  
Laura Rayón ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Critically Ill ◽  
Cox Regression ◽  
Chronic Liver ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

scholarly journals Fast-Track Programs in Total Hip and Knee Replacement at Swedish Hospitals—Influence on 2-Year Risk of Revision and Mortality

2021 ◽  
Vol 10 (8) ◽  
pp. 1680
Author(s):  
Urban Berg ◽  
Annette W-Dahl ◽  
Anna Nilsdotter ◽  
Emma Nauclér ◽  
Martin Sundberg ◽  
...  
Keyword(s):  
Fast Track ◽  
Cox Regression ◽  
Cox Regression Analysis ◽  
Total Hip ◽  
Total Knee Replacements ◽  
Risk Of Death ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Hip And Knee Arthroplasty ◽  
Total Knee

Purpose: We aimed to study the influence of fast-track care programs in total hip and total knee replacements (THR and TKR) at Swedish hospitals on the risk of revision and mortality within 2 years after the operation. Methods: Data were collected from the Swedish Hip and Knee Arthroplasty Registers (SHAR and SKAR), including 67,913 THR and 59,268 TKR operations from 2011 to 2015 on patients with osteoarthritis. Operations from 2011 to 2015 Revision and mortality in the fast-track group were compared with non-fast-track using Kaplan–Meier survival analysis and Cox regression analysis with adjustments. Results: The hazard ratio (HR) for revision within 2 years after THR with fast-track was 1.19 (CI: 1.03–1.39), indicating increased risk, whereas no increased risk was found in TKR (HR 0.91; CI: 0.79–1.06). The risk of death within 2 years was estimated with a HR of 0.85 (CI: 0.74–0.97) for TKR and 0.96 (CI: 0.85–1.09) for THR in fast-track hospitals compared to non-fast-track. Conclusions: Fast-track programs at Swedish hospitals were associated with an increased risk of revision in THR but not in TKR, while we found the mortality to be lower (TKR) or similar (THR) as compared to non-fast track.

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