scholarly journals Results of the ADIUVO Study, the First Randomized Trial on Adjuvant Mitotane in Adrenocortical Carcinoma Patients

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A166-A167
Author(s):  
Massimo Terzolo ◽  
Martin Fassnacht ◽  
Paola Perotti ◽  
Rossella Libe ◽  
André Lacroix ◽  
...  
Keyword(s):  
Observational Study ◽  
Adrenocortical Carcinoma ◽  
Multivariable Analysis ◽  
Stage I ◽  
Controlled Study ◽  
Intermediate Risk ◽  
Ki 67 ◽  
Risk Of Recurrence ◽  
Randomized Controlled ◽  
Baseline Characteristics

Abstract Background: The ESE-ENSAT guidelines on the management of adrenocortical carcinoma (ACC) suggest adjuvant mitotane for patients at high risk of recurrence following radical surgery. This indication has a limited evidence base, lacking results from randomized controlled trials. No suggestion for or against adjuvant mitotane in low-risk patients was given, since studies did not stratify patients for prognosis. The randomized controlled study ADIUVO compared the efficacy of adjuvant mitotane treatment vs. observation in prolonging recurrence-free survival (RFS) in ACC patients at low-intermediate risk of recurrence. Methods: The main inclusion criteria were: stage I-III ACC, R0 surgery, and Ki-67 ≤10%. Patients were randomly assigned 1:1 to adjuvant mitotane (MIT) or observation (OBS). The primary endpoint of the study was RFS. Patients who refused randomization were offered inclusion in the ADIUVO OBSERVATIONAL study. In this prospective, observational study, patients were managed as in the ADIUVO study. A total of 91 patients were enrolled in ADIUVO, 45 in the MIT and 46 in the OBS arm. Baseline characteristics of patients were perfectly matched between the 2 arms: median age, 51 vs. 50.5 years; female, 73% vs. 67%; stage I, 20% vs. 26%; stage II, 67% vs. 63%, stage III, 13% vs. 11%; ACC secretion 44% vs. 36%; Weiss 5 vs. 5; respectively. In ADIUVO OBSERVATIONAL, 42 patients were treated with mitotane and 53 were untreated. Baseline characteristics of patients were matched between the 2 groups and with MIT and OBS groups in ADIUVO. Thus, the ADIUVO OBSERVATIONAL cohorts could be analyzed in parallel to those of ADIUVO. Results: In the ADIUVO study, recurrences were 8 in the MIT and 11 in the OBS arm, while deaths were 2 and 5, respectively. RFS and overall survival (OS) did not significantly differ between the 2 arms. Tumor size was a predictor of RFS in multivariable analysis. In the OBS arm, the HR for recurrence was 1.321 (95%CI, 0.55–3.32, p=0.54) and HR for death 2.171 (95%CI, 0.52–12.12, p=0.29). The survival analysis in the ADIUVO OBSERVATIONAL study confirmed the findings of ADIUVO. Given the outcome of both studies, the NNT is 55. Conclusions: ACC patients at low-intermediate risk of recurrence after surgery are a minority; however, they show a far better prognosis than expected (5-year RFS is about 75%) and do not benefit significantly from adjuvant mitotane. The results of the ADIUVO study do not support routine use of adjuvant mitotane in this subset of patients, who may thus avoid a potentially toxic treatment. This is an important step toward personalization of ACC care.

scholarly journals Efficacy of Once Daily versus Divided Daily Administration of Low Daily Dosage (15 mg/Day) of Methimazole in the Induction of Euthyroidism in Graves’ Hyperthyroidism: A Randomized Controlled Study

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Sutin Sriussadaporn ◽  
Wanwaroon Pumchumpol ◽  
Raweewan Lertwattanarak ◽  
Tada Kunavisarut
Keyword(s):  
Controlled Study ◽  
Once Daily ◽  
Randomized Controlled ◽  
Daily Dose ◽  
Cumulative Rate ◽  
Baseline Characteristics ◽  
Serum Thyroid Hormone ◽  
Thyroid Hormone Levels ◽  
Daily Dose Regimen ◽  
Clinical Trials Registry

Background. Previous studies used unequal or high daily dosages of methimazole (MMI) to compare the efficacy of once daily dose regimen (OD-MMI) with that of divided daily doses regimen (DD-MMI) in inducing euthyroidism. Objectives. To compare the efficacy of OD-MMI to that of DD-MMI using low daily dosage of MMI in inducing euthyroidism. Methods. Fifty patients with clinically nonsevere Graves’ hyperthyroidism were randomized to be treated with 15 mg/day OD-MMI or 15 mg/day DD-MMI. Results. 21 cases (84%) in OD-MMI and 23 cases (92%) in DD-MMI were eligible for analyses. During the treatment, there was no difference in baseline characteristics, serum FT3 and FT4 reductions, and cumulative rate of achieving euthyroidism (4.8% versus 4.3%, 28.6% versus 34.8%, 71.4% versus 82.6%, and 85.7% versus 87.0% at 2, 4, 8, and 12 weeks, resp.) between both regimens. Hypothyroidism developed in DD-MMI significantly more than in OD-MMI (17.4% versus 0%, p<0.05). Conclusions. Treatment with MMI at a low daily dosage of 15 mg/day OD-MMI is as effective as DD-MMI in the reduction of serum thyroid hormone levels and induction of euthyroidism. The OD-MMI regimen is preferable to the DD-MMI regimen in the treatment of clinically nonsevere Graves’ hyperthyroidism. This trial is registered with Thai Clinical Trials Registry: TCTR20170529001.

scholarly journals Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Stefan Hatzl ◽  
Alexander C. Reisinger ◽  
Florian Posch ◽  
Juergen Prattes ◽  
Martin Stradner ◽  
...  
Keyword(s):  
Observational Study ◽  
Primary Outcome ◽  
Antifungal Prophylaxis ◽  
Secondary Outcome ◽  
Medical Mycology ◽  
Pulmonary Aspergillosis ◽  
Randomized Controlled ◽  
Prophylaxis Group ◽  
Baseline Characteristics ◽  
Propensity Score Adjustment

Abstract Background Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. Methods In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. Results We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2–9.7) in the MAFP group and 17.5% (95% CI 9.6–31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01–0.63; p = 0.017). Conclusion In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Circulating tumor DNA to detect minimal residual disease, response to adjuvant therapy, and identify patients at high risk of recurrence in patients with stage I-III CRC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4009-4009
Author(s):  
Noelia Tarazona ◽  
Tenna V Henriksen ◽  
Juan Antonio Carbonell-Asins ◽  
Thomas Reinert ◽  
Shruti Sharma ◽  
...  
Keyword(s):  
High Risk ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Multivariable Analysis ◽  
Circulating Tumor Dna ◽  
Stage I ◽  
Plasma Samples ◽  
Risk Of Recurrence ◽  
Tumor Dna ◽  
Minimal Residual

4009 Background: The clinical utility of tracking circulating tumor DNA (ctDNA) as a non-invasive biomarker for detecting minimal residual disease (MRD) and stratifying patients based on their risk of developing relapse has been well established in colorectal cancer (CRC). This study evaluates the detection and longitudinal monitoring of ctDNA in CRC patients pre- and post-operatively, during and after adjuvant chemotherapy (ACT). Methods: The prospective, multicenter cohort study recruited patients (n = 193) diagnosed with resected stage I-III CRC. Plasma samples (n = 1052) were collected at various timepoints with a median follow up of 21.6 months (4.6-38.5 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic mutations identified. Multiplex PCR assays were designed to 16 tumor-specific single-nucleotide variants to track ctDNA in plasma samples. The study evaluated the relationship between ctDNA status and clinical outcomes including radiologic imaging. Cox regression was used to calculate recurrence-free survival (RFS) in patients stratified by ctDNA status postoperatively and post-ACT. Multivariable analysis was performed with all clinical variables. Best model was selected according to Akaike Information Criterion. Results: Pre-operatively ctDNA was detected in 90% (n = 166/185) of the patients. Post-operative ctDNA status prior to ACT was assessed in 152 patients, of which 9.2% (14/152) were identified to be MRD-positive and 78.5% (11/14) eventually relapsed. In contrast, 10.1% (14/138) of MRD-negative cases relapsed (HR: 16.53; 95% CI: 7.19-38.02; p < 0.001). Longitudinal ctDNA-positive status, post-ACT (n = 84) and post definitive therapy (n = 139) was associated with a 27.92 HR (95% CI: 9.16-85.11; p < 0.001) and a 47.52 HR (95% CI: 17.34-130.3.; p < 0.001), respectively. In the multivariable analysis, longitudinal ctDNA status was the only significant prognostic factor associated with RFS (HR: 53.19, 95% CI: 18.87-149.90; p < 0.001). Serial ctDNA analysis detected MRD up to a median of 9.08 months (0.56-16.5 months) ahead of radiologic relapse with a sensitivity of 79.1% and specificity of 99%. Conclusions: Postoperative ctDNA analyses detect patients with high-risk of recurrence, with near 100% specificity. Early detection of MRD and longitudinal monitoring of ctDNA could guide treatment decisions. Intervention trials to assess the clinical benefit of ctDNA use are underway.

scholarly journals Cardio-Respiratory Events and Food Autonomy Responses to Early Uni-Modal Orofacial Stimulation in Very Premature Babies: A Randomized, Controlled Study

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1188
Author(s):  
Sahra Méziane ◽  
Véronique Brévaut-Malaty ◽  
Aurélie Garbi ◽  
Muriel Busuttil ◽  
Gaelle Sorin ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Controlled Study ◽  
Control Group ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Randomized Controlled ◽  
Respiratory Events ◽  
Experimental Group

Uni-modal orofacial stimulation (OFS) for preventing very preterm infants’ oral disorders is highly controversial. Our study sought to demonstrate that OFS reduced cardio-respiratory events and improved food autonomy in a population of very preterm infants. Our study was randomized, controlled, prospective, and unicentric. The preterm included were born between 26–29 weeks gestational age (GA) with a corrected postnatal age <33 weeks GA. They were randomized into two groups: the experimental group underwent OFS, according to a protocol established, over 10 consecutive days, and the control group underwent no OFS. The primary outcome was the number of cardiorespiratory events: apnea–bradycardia (with or without desaturations) or number of isolated desaturations, which were evaluated at four separate times. Measurements occurred during the first, fourth and eighth independent feedings. Seventeen patients were included in the experimental group and 18 in the control group. The number of cardiorespiratory events for all independent feeding times was significantly reduced in the OFS group (p = 0.003) with univariate analysis, but not with multivariable analysis. The quantity of milk ingested during the first autonomous feeding was higher in the experimental group. The acquisition of food autonomy and the duration of hospitalization were similar in the two groups. While our study does not affirm that an early unimodal OFS improves premature infants’ cardiorespiratory evolution and/or the acquisition of food autonomy, it does indicate an improved food efficiency during their first autonomous feedings.

scholarly journals Adrenocortical Cancer: A 20-Year Experience of a Single Referral Center in Prognosis and Outcomes

2021 ◽  
Vol 53 (11) ◽  
pp. 709-716
Author(s):  
George Zografos ◽  
Eva Kassi ◽  
Christos Parianos ◽  
Georgios Kyriakopoulos ◽  
Ioannis D. Kostakis ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Multivariable Analysis ◽  
Morphological Characteristics ◽  
Gene Profiling ◽  
Disease Stage ◽  
Adrenocortical Cancer ◽  
Ki 67 ◽  
Female Ratio ◽  
Immunohistochemical Markers ◽  
Staging Systems

AbstractAdrenocortical carcinoma (ACC) is a rare but very aggressive endocrine malignancy with poor survival. Histopathology is important for diagnosis, while in some cases immunohistochemical markers and gene profiling of the resected tumor may be superior to current staging systems to determine prognosis. We aimed to present the 20-year experience at a tertiary hospital in patients with ACCs and correlate the immunohistochemical characteristics of ACCs with the clinical and morphological characteristics of the tumors and the survival of the patients. Forty-five patients with ACC were included in the study. All the resections were R0. The tumor size and weight, the disease stage (ENSAT classification), Weiss score and Helsinki score were examined along with immunohistochemical expression of inhibin-A, melan A, calretinin, Ki67, synaptophysin, p53, vimentin, CKAE1/AE3. The male to female ratio was 1:1.37. The median age at diagnosis was 55.5 years (IQR 19–77). The median size of ACCs was 9 cm (IQR 3.5–22 cm) and the median weight 127 g (IQR 18–1400 g). The median follow up period was 18 months (IQR 1–96). Ki67 varied from<1% to 75% (median: 16.4%). The expression of melan-A and lower expression of Ki-67 (≤4) were independently associated with longer OS time (p=0.01 and p=0.04, respectively). In multivariable analysis, tumor volume>400 cm3 (p=0.046), Weiss score>5 (p=0.007) and overexpression of p53 (p=0.036) were independent risk factors for shorter survival. Adrenocortical carcinoma is a rare and very aggressive endocrine malignancy. The most important factors that determine long-term prognosis of ACC are the disease stage at diagnosis, the Weiss score, and the Ki67 index. Immunohistochemical markers such as melan A could also serve as prognostic factors.

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