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Digestive and Liver Disease : Official... Dec 2023Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment of ICIs-associated colitis/diarrhea and outcomes.
METHODS
PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies which investigated the treatment and outcomes of colitis/diarrhea developing in patients who received ICIs. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea as well as the pooled rates of response to treatment, mortality, and ICIs permanent discontinuation and restarts in patients with ICIs-associated colitis/diarrhea were estimated using a random-effects model.
RESULTS
Among the 11,492 papers initially identified, 27 studies were included. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea were 17%, 3%, 17%, 13%, and 15%, respectively. The pooled rates of overall response, response to corticosteroid therapy, and response to biological agents were 88%, 50%, and 96%, respectively. The pooled short-term mortality in patients with ICIs-associated colitis/diarrhea was 2%. The pooled incidences of ICIs permanent discontinuation and restarts were 43% and 33%, respectively.
CONCLUSION
ICIs-associated colitis/diarrhea is common, but rarely lethal. Half of them are responsive to corticosteroid therapy. There is a fairly high rate of response to biological agents in steroid-refractory colitis/diarrhea patients.
Topics: Humans; Immune Checkpoint Inhibitors; Colitis; Diarrhea; Treatment Outcome; Adrenal Cortex Hormones
PubMed: 36894390
DOI: 10.1016/j.dld.2023.02.016 -
International Journal of Hyperthermia :... 2023To evaluate the safety and clinical efficacy of image-guided radiofrequency ablation (RFA) in patients exhibiting adrenal metastatic tumors (AMTs). (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the safety and clinical efficacy of image-guided radiofrequency ablation (RFA) in patients exhibiting adrenal metastatic tumors (AMTs).
METHODS
The PubMed, Web of Science, and Wanfang databases were searched for relevant studies published as of November 2022, and study results were pooled for subsequent analysis. The endpoints of this meta-analysis included primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year overall survival (OS) rates.
RESULTS
This analysis incorporated 11 studies enrolling 351 patients that underwent RFA treatment for 373 AMTs. The pooled primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year OS rates in these patients were 84%, 91%, 4%, 6%, 7%, 19%, 82%, and 46%, respectively. The 1-year OS ( = 75.2%, = 0.003) and 3-year OS ( = 81.4%, = 0.001) endpoints were subject to significant heterogeneity. Subgroup analyses suggested that primary technical success rates were < 80% in patients with tumors exhibiting a mean diameter ≥ 4 cm. Guidance type and tumor size had no impact on a hypertensive crisis or local recurrence rates.
CONCLUSIONS
These data indicate that image-guided RFA represents a safe and effective means of treating AMTs.
Topics: Humans; Pneumothorax; Radiofrequency Ablation; Treatment Outcome; Adrenal Gland Neoplasms; Survival Rate; Catheter Ablation; Liver Neoplasms; Carcinoma, Hepatocellular
PubMed: 36889697
DOI: 10.1080/02656736.2023.2185575 -
World Journal of Surgical Oncology Mar 2023Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative... (Meta-Analysis)
Meta-Analysis
PURPOSE
Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function.
METHODS
A systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE.
RESULTS
Sixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95% CI, 0.622-0.703; P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95% CI, 0.503-0.620; P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator's definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95% CI, 0.527-0.961; P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95% CI, 0.393-0.746; P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95% CI, 0.022-0.783; P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant.
CONCLUSIONS
In patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.
Topics: Humans; Hyperprolactinemia; Somatotrophs; Pituitary Hormones; Endoscopy; Hypopituitarism; Pituitary Neoplasms
PubMed: 36859291
DOI: 10.1186/s12957-023-02958-2 -
Blood Jun 2023The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear,... (Meta-Analysis)
Meta-Analysis
The benefit associated with the incorporation of vincristine-corticosteroid pulses in maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing the frequency of vincristine-steroid pulses during maintenance for pediatric patients newly diagnosed with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from 25 publications (12 513 patients), and assessed the risk of bias. We created historical and contemporary subgroups; the latter included trials providing both a version of Protocol III from the early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.85-1.09), which differed significantly from historical trials (HR, 0.79; 95% CI, 0.68-0.91; P = .04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however increased odds of grade 3+ nonhepatic toxicity in the high-pulse frequency group (odds ratio, 1.31; 95% CI, 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide the development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance among patients not in clinical trials, particularly those experiencing toxicity.
Topics: Humans; Child; Vincristine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Adrenal Cortex Hormones; Steroids; Progression-Free Survival; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 36821772
DOI: 10.1182/blood.2022018899 -
Endocrine-related Cancer Apr 2023Histopathological differentiation in pediatric adrenocortical carcinoma (pACC) is difficult and clinical prediction and stratification scores are not evaluated yet.... (Review)
Review
Histopathological differentiation in pediatric adrenocortical carcinoma (pACC) is difficult and clinical prediction and stratification scores are not evaluated yet. Therefore, this review aims to summarize current evidence on the value and accuracy of the two commonly used scoring systems (Weiss/Armed Forces Institute of Pathology (AFIP)) pACC. On this base, one might be able to evaluate if patients may benefit from a unique scoring system. For this, we performed a systematic review of the published literature and included 128 patients in our analysis. The majority (72%) of the pACCs had a good clinical course. The follow-up time ranged from 0 to 420 months with a mean age of 5.6 years at diagnosis. Patients with a good clinical course were younger (mean 4.8 years) than patients with a poor outcome (mean 7.6 years). Comparing the two scoring systems, the specificity of the Weiss score was very low (25%), whereas the sensitivity was 100%. According to the AFIP score, specificity (77%) was higher than the Weiss score, whereas the sensitivity of the AFIP score was minimal lower with 92%. Age differences were recognizable as the specificity was lower in infants <4 years (20%) than in older children (32%). In contrast, the specificity of the AFIP score was higher in infants <4 years (82%) than in older age groups (76%). Summarizing our results, we could show that the Weiss score is not a suitable tool for the prediction of malignancy in pACC in comparison with the AFIP score, but further efforts may seek to ensure early and accurate stratification through augmented scoring.
Topics: Infant; Child; Humans; Aged; Child, Preschool; Prognosis; Adrenocortical Carcinoma; Disease Progression; Adrenal Cortex Neoplasms
PubMed: 36753311
DOI: 10.1530/ERC-22-0259 -
The Journal of Clinical Endocrinology... Jun 2023Adrenal hyperfunction is associated with an increased risk of cardiometabolic complications in subjects with adrenal incidentaloma (AI). Reliable prevalence estimates of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Adrenal hyperfunction is associated with an increased risk of cardiometabolic complications in subjects with adrenal incidentaloma (AI). Reliable prevalence estimates of functioning AIs are important to direct resources allocations.
OBJECTIVE
To assess the prevalence of autonomous/possible autonomous cortisol secretion (ACS), primary aldosteronism (PA), pheochromocytoma (PHEO), and Cushing syndrome (CS) in patients with AI.
METHODS
We performed a comprehensive search of multiple databases (PubMed, Ovid MEDLINE, Web of Science) for potentially relevant studies without language restriction, up to February 2022. Of the 1661 publications evaluated at title and abstract levels, 161 were examined as full text and 36 were included. Study level clinical data were extracted by 3 independent reviewers.
RESULTS
The overall prevalence of functioning AIs was 27.5% (95% CI 23.0, 32.5). ACS/possible ACS, with a prevalence of 11.7% (95% CI 8.6, 15.7), was the most frequent hormonal alteration, while PA occurred in 4.4% of the patients (95% CI 3.1, 6.2). Subgroup analysis showed that PA was more prevalent in patients from Asia than in patients from Europe/America; in contrast, ACS/possible ACS had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of ACS/possible ACS was influenced by the proportion of female patients, while the prevalence of PA was positively associated with the proportion of patients with hypertension and the publication year. Finally, PHEO and CS prevalence were 3.8% (95% CI 2.8, 5.0) and 3.1% (95% CI 2.3, 4.3) respectively.
CONCLUSION
This meta-analysis provides extensive data on the prevalence of functioning AIs and the factors affecting heterogeneity in prevalence estimates.
Topics: Humans; Female; Adrenal Gland Neoplasms; Prevalence; Cushing Syndrome; Hypertension; Pheochromocytoma; Hydrocortisone
PubMed: 36718682
DOI: 10.1210/clinem/dgad044 -
The Cochrane Database of Systematic... Jan 2023Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality... (Review)
Review
BACKGROUND
Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.
OBJECTIVES
To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022. SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence). Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence). Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence).
AUTHORS' CONCLUSIONS
There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.
Topics: Humans; Adult; Adolescent; Quality of Life; Modafinil; Adrenal Cortex Hormones; Neoplasms; Dexamethasone; Fatigue
PubMed: 36688471
DOI: 10.1002/14651858.CD013782.pub2 -
Life (Basel, Switzerland) Nov 2022(1) Background: This study aimed to develop a comprehensive understanding of the treatment-related adverse events when using PD-1 or PD-L1 inhibitors in triple-negative... (Review)
Review
(1) Background: This study aimed to develop a comprehensive understanding of the treatment-related adverse events when using PD-1 or PD-L1 inhibitors in triple-negative breast cancer (TNBC). (2) Methods: We conducted a meta-analysis of Phase II/III randomized clinical trials. Studies were searched for using PubMed, Embase, and Cochrane Library from 1 March 1980 till 30 June 2022. Data on adverse events were mainly extracted from ClinicalTrials.gov and published articles. A generalized linear mixed model with the logit transformation was employed to obtain the overall incidence of adverse events across all studies. For serious adverse events with low incidences, the Peto method was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) in the PD-1 or PD-L1 inhibitors groups compared to the control groups. (3) Results: Nine studies were included in the meta-analysis, including a total of 2941 TNBC patients treated with PD-1 or PD-L1 inhibitors (including atezolizumab, pembrolizumab and durvalumab) and 2339 patients in the control groups. Chemotherapy alone was the control group in all studies. The average incidences of all serious immune-related adverse events of interest (hypothyroidism, hyperthyroidism, pneumonitis, pruritus, rash) were less than 1%, except for adrenal insufficiency (1.70%, 95%CI: 0.50-5.61%) in the PD-1 or PD-L1 groups. PD-1 or PD-L1 inhibitors significantly increased the risk of serious pneumonitis (OR = 2.52, 95%CI: 1.02-6.26), hypothyroidism (OR = 5.92, 95%CI: 1.22-28.86), alanine aminotransferase (ALT) elevation (OR = 1.66, 95%CI: 1.12-2.45), and adrenal insufficiency (OR = 18.81, 95%CI: 3.42-103.40). For non-serious adverse events, the patients treated with PD-1 or PD-L1 inhibitors had higher risk of aspartate aminotransferase (AST) elevation (OR =1.26, 95%CI: 1.02-1.57), hypothyroidism (OR = 3.63, 95%CI: 2.92-4.51), pruritus (OR = 1.84, 95%CI: 1.30-2.59), rash (OR = 1.29, 95%CI: 1.08-1.55), and fever (OR = 1.77, 95%CI: 1.13-2.77), compared with chemotherapy alone. (4) Conclusions: The incidence of serious immune-related adverse events in PD-1 or PD-L1 inhibitors groups is low but significantly higher than in chemotherapy groups. When using PD-1 or PD-L1 inhibitors for the treatment of TNBC, serious pneumonitis, hypothyroidism, ALT elevation, and adrenal insufficiency should be considered. Non-serious adverse events, such as AST elevation, rash, and fever, should also be taken into consideration.
PubMed: 36556355
DOI: 10.3390/life12121990 -
Clinical Genitourinary Cancer Feb 2023Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare... (Review)
Review
A Systematic Review of Published Clinical Trials in the Systemic Treatment of Adrenocortical Carcinoma: An Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors.
Adrenocortical carcinoma (ACC) is a very rare endocrine cancer and is associated with a poor prognosis. There is a paucity of randomized clinical trials for this rare disease. We aimed to perform a systematic review of the literature on systemic therapy options in different stages of ACC. A systematic review was performed using Pubmed and Embase databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 24 trials of systemic therapy in the treatment of ACC were identified and included in this review. Only one clinical trial in the adjuvant setting was identified, the negative phase III trial ADIUVO, which tested mitotane in low to intermediate-risk ACC patients. In the treatment of advanced ACC, cisplatin-based chemotherapy was evaluated in small and non-randomized phase II trials, and response rates ranged from 21% to 53.5%. The phase III trial FIRM-ACT compared etoposide, doxorubicin, cisplatin, and mitotane versus treatment with streptozotocin and mitotane and showed no difference in OS, but higher RR and PFS were reported with the multi-drug regimen. Six clinical trials of immunotherapy and seven studies of targeted therapy in advanced ACC were included, with modest activity and no phase 3 trials were identified. Treatment recommendations of ACC are based on retrospective and small studies with limited systemic therapy options. International and multi-center collaboration is essential to expand clinical research and improve outcomes.
Topics: Humans; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Cisplatin; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36376169
DOI: 10.1016/j.clgc.2022.10.011 -
Annals of Surgical Oncology Feb 2023Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for adrenocortical carcinomas. This study aims to evaluate the safety and efficacy of laparoscopic surgery and open surgery in the management of adrenocortical carcinoma.
METHODS
The Cochrane, Embase, PubMed, Scopus, and Web of Science databases were searched for articles from inception to May 2022, by two independent reviewers using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The review was registered prospectively on the PROSPERO database (CRD42022316050).
RESULTS
From 183 studies screened, 11 studies met the eligibility criteria, with a total of 1617 patients with adrenocortical carcinoma undergoing either laparoscopic surgery (n = 472) or open surgery (n = 1145). Open surgery demonstrated a lower rate of positive resection margin compared with laparoscopic surgery (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.10-2.10; I = 0%). Additionally, open surgery had more favorable overall survival (OR 0.56, 95% CI 0.44-0.72; I = 0%) and recurrence-free rates (OR 0.60, 95% CI 0.42-0.85; I = 38%) than laparoscopic surgery at 3 years. Hospital stay was shorter for laparoscopic surgery than open surgery (mean difference - 2.49 days, 95% CI - 2.95 to - 2.04; I = 45%).
CONCLUSIONS
Open surgery should still be considered the standard operative approach; however, laparoscopic surgery could be regarded as an effective and safe operation for selected adrenocortical carcinoma cases with appropriate laparoscopic expertise. Further randomized controlled studies with tumor stage- and resection margin-dependent survival analysis are necessary to ascertain the safety and efficacy of the treatment.
Topics: Humans; Adrenocortical Carcinoma; Margins of Excision; Laparoscopy; Adrenal Cortex Neoplasms; Treatment Outcome
PubMed: 36344710
DOI: 10.1245/s10434-022-12711-w