Local recurrence
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Olaparib treatment significantly improved objective response rate (primary end point) and progression-free survival versus nonplatinum chemotherapy in patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer in the open-label phase III SOLO3 trial (ClinicalTrials.gov identifier: NCT02282020). We report final overall survival (OS; prespecified secondary end point), post hoc OS analysis by number of previous chemotherapy lines, and exploratory BRCA reversion mutation analysis. Two hundred sixty-six patients were randomly assigned 2:1 to olaparib tablets (300 mg twice daily; n = 178) or physician's choice of single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan; n = 88). OS was similar with olaparib versus chemotherapy (hazard ratio [HR], 1.07 [95% CI, 0.76 to 1.49]; P = .71, median 34.9 and 32.9 months, respectively, full analysis set). OS with olaparib was favorable in patients with two previous chemotherapy lines (HR, 0.83 [olaparib v chemotherapy] [95% CI, 0.51 to 1.38]; median 37.9 v 28.8 months); however, a potential detrimental effect was seen in patients with at least three previous chemotherapy lines (HR, 1.33 [95% CI, 0.84 to 2.18]; median 29.9 v 39.4 months). BRCA reversion mutations might have contributed to this finding. No patient randomly assigned to olaparib with a BRCA reversion mutation detected at baseline (6 of 170 [3.5%]) achieved an objective tumor response.
- MeSH
- deoxycytidin analogy a deriváty aplikace a dávkování MeSH
- doba přežití bez progrese choroby MeSH
- dospělí MeSH
- doxorubicin analogy a deriváty aplikace a dávkování MeSH
- ftalaziny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- gemcitabin MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * farmakoterapie MeSH
- nádory vaječníků * farmakoterapie genetika mortalita patologie MeSH
- paclitaxel aplikace a dávkování MeSH
- PARP inhibitory * terapeutické užití škodlivé účinky MeSH
- piperaziny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- polyethylenglykoly aplikace a dávkování MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- senioři MeSH
- topotekan aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: This study aimed to evaluate local control (LC) of tumors, patient overall survival (OS), and the safety of stereotactic radiosurgery (SRS) for esophageal cancer brain metastases (EBMs). METHODS: This retrospective cohort study used data from 15 International Radiosurgery Research Foundation facilities encompassing 67 patients with 185 EBMs managed using SRS between January 2000 and May 2022. The median patient age was 63 years, with a male predominance (92.5%). Most patients (64.2%) had a single brain metastasis, while 7.5% had more than 5 metastases. The median tumor volume was 0.9 cm3, and the median margin dose delivered to the tumor was 20 Gy. RESULTS: The median OS post-SRS was 15.2 months, with 1- and 2-year OS rates of 65.7% and 32.3%, respectively. A significant inverse correlation was found between the number of EBMs and OS in the univariable analysis. LC rates at 1 and 2 years were 89% and 76%, respectively. Adverse radiation effects (AREs) were observed in 17.9% of patients, with 13.4% being mild and transient and 4.5% severely symptomatic (Common Terminology Criteria for Adverse Events grade 3). New intracranial disease developed in 58.2% of patients, with 1- and 2-year rates of 58% and 73%, respectively. CONCLUSIONS: SRS for EBMs demonstrated high survival rates and effective tumor control, with a low incidence of severe AREs. These findings highlight the potential role of SRS in the multidisciplinary multimodality management paradigm of EBM.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádory jícnu * patologie mortalita MeSH
- nádory mozku * sekundární radioterapie mortalita MeSH
- radiochirurgie * metody škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Adult granulosa cell tumors (AGCTs) of the ovary are characterized by their propensity for late recurrences and are primarily managed surgically due to the limited efficacy of systemic treatment. The FOXL2 p.C134W somatic mutation has been identified in ∼95% of AGCT cases, and TERT promoter alterations have been linked to worse overall survival. This study highlights the potential prognostic significance of FOXO1 mutations, suggesting that they may be associated with poorer overall survival and shorter time to recurrence. A total of 183 primary AGCTs and 44 recurrences without corresponding primary tumors were analyzed. The primary AGCTs were categorized into 3 groups: 77 nonrecurrent tumors, 18 tumors that later recurred (including 9 cases with matched primary-recurrence pairs), and 88 tumors with unknown recurrence status. Targeted next-generation sequencing was conducted on 786 cancer-related genes to investigate their genetic profile. The study aimed to identify the molecular alterations associated with AGCT pathogenesis and recurrence rate, comparing primary versus recurrent tumors, and primary recurrent versus primary nonrecurrent cases. Our findings confirmed the high prevalence (99%) of the FOXL2 p.C134W mutation in AGCTs. Secondary truncating FOXL2 mutations were observed in 5% of cases. Two cases with typical AGCT morphology were FOXL2 wild-type, harboring mutations in KRAS or KMT2D instead, suggesting alternative genetic pathways. TERT promoter mutations were found in 43% of cases, more frequently in recurrences. Other recurrent mutations detected in the cohort included KMT2D (10%), FOXO1 (7%), CHEK2 (5%), TP53 (3.5%), PIK3CA (3.5%), and AKT1 (3%). Two recurrent, FOXL2-mutated cases also carried DICER1 mutations. One tumor exhibited MSI-high status and a tumor mutation burden of 19 mut/Mb.Our results indicate the need for further investigation into the role of FOXO1 as a potential prognostic marker in AGCTs.
- MeSH
- dospělí MeSH
- forkhead box protein O1 * genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * genetika MeSH
- mutace * MeSH
- nádor z folikulárních buněk * genetika patologie MeSH
- nádory vaječníků * genetika patologie MeSH
- prognóza MeSH
- progrese nemoci MeSH
- protein FOXL2 genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- telomerasa genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.
- MeSH
- brachyterapie * metody MeSH
- chemoradioterapie * MeSH
- cisplatina terapeutické užití MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * radioterapie MeSH
- magnetická rezonanční tomografie * MeSH
- nádory děložního čípku * radioterapie diagnostické zobrazování patologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS: Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS: Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.
- MeSH
- difúzní velkobuněčný B-lymfom * radioterapie patologie genetika MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * patologie MeSH
- mladý dospělý MeSH
- protoonkogenní proteiny c-bcl-2 genetika MeSH
- protoonkogenní proteiny c-myc genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- translokace genetická MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND AND OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical challenge, particularly when failing bacillus Calmette-Guérin (BCG) therapy, necessitating alternative treatments. Despite radical cystectomy being the recommended treatment, many patients are unfit or unwilling to undergo this invasive procedure, highlighting the need for effective bladder-sparing therapies. This review aims to summarize and report the evidence on the efficacy and to estimate the costs of bladder-preserving strategies used in NMIBC recurrence after failure of intravesical BCG therapy. METHODS: We systematically searched online databases for prospective studies investigating intravesical therapy, systemic therapy, or combination of both in patients treated previously with BCG. Owing to significant heterogeneity across the studies, a meta-analysis was inappropriate. A sensitivity analysis was performed in an exploratory manner. We used a decision-analytic Markov model to compare novel U.S. Food and Drug Administration-approved treatments with a 2-yr time horizon. KEY FINDINGS AND LIMITATIONS: A total of 57 studies published between 1998 and 2024, with 68 unique study arms and consisting of 2589 patients, were identified. The 3-mo overall response rate (ORR) across all studies, complete response rate (CRR) in concomitant carcinoma in situ (CIS) or CIS only disease, and recurrence-free rate (RFR) in papillary disease were estimated to be 52.4% (95% confidence interval [CI]: 45.4-59.2), 52.8% (95% CI: 42.9-62.6), and 26.4% (95% CI: 13.3-45.6), respectively. The 12-mo ORR, CRR, and RFR were estimated to be 78% (95% CI: 52.9-91.8), 27.8% (95% CI: 21.3-35.4), and 25.4% (95% CI: 18.2-34.2), respectively. The progression rate was estimated to be 13% (95% CI: 9-18.2). The mean proportion of patients treated with radical cystectomy was estimated to be 24.7 (range 0-85.7). The reported toxicity grades were overall mild, with a median of 3.4% (range 0-33.3%) participants experiencing a dose limiting toxicity. Compared with using radical cystectomy to treat patients failing BCG therapy, at a willingness-to-pay threshold of 100 000 USD, nadofaragene firadenovec was cost effective, with an incremental cost-effectiveness ratio (ICER) of 10 014 USD per quality-adjusted life year (QALY), while nogapendekin alfa inbakicept was less cost effective than nadofaragene firadenovec (ICER of 44 602 USD per QALY). Pembrolizumab, which dominated, was both less costly and more effective than the other strategies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Salvage bladder-sparing therapies show a response rate of around 50% at 3 mo in patients with NMIBC failing BCG. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life. The findings of our review highlight the need for novel, more effective therapeutic strategies. PATIENT SUMMARY: In this study, we reviewed the evidence on the efficacy of bladder-preserving strategies used in patients with bladder cancer recurrence after failing bacillus Calmette-Guérin (BCG) therapy. We found that these strategies show a response rate of around 50% at 3 mo. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life.
- MeSH
- adjuvancia imunologická * terapeutické užití ekonomika MeSH
- analýza nákladů a výnosů * MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití ekonomika MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie terapie ekonomika MeSH
- neúspěšná terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer. We hypothesised that nivolumab/ipilimumab would be more effective than adjuvant chemotherapy in high-risk (ypN+ and/or R1) patients with gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and resection. PATIENTS AND METHODS: VESTIGE was an academic international, multicentre, open-label, randomised phase II trial evaluating the efficacy of adjuvant nivolumab/ipilimumab versus chemotherapy in gastro-oesophageal adenocarcinoma at high risk of recurrence. Patients were randomised 1 : 1 to receive standard adjuvant chemotherapy (same regimen as neoadjuvant) or nivolumab 3 mg/kg intravenously (i.v.) every 2 weeks plus ipilimumab 1 mg/kg i.v. every 6 weeks for 1 year. Key inclusion criteria included ypN+ and/or R1 status after neoadjuvant chemotherapy plus surgery. The primary endpoint was disease-free survival in the intent-to-treat population. Secondary endpoints included overall survival, locoregional and distant failure rates, and safety according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. RESULTS: The independent Data Monitoring Committee reviewed data from 189 of the planned 240 patients in June 2022 and recommended stopping recruitment due to futility. At the time of final analysis, median follow-up was 25.3 months for 195 patients (98 nivolumab/ipilimumab and 97 chemotherapy). Median disease-free survival for the nivolumab/ipilimumab group was 11.4 months [95% confidence interval (CI) 8.4-16.8 months] versus 20.8 months (95% CI 15.0-29.9 months) for the chemotherapy group, hazard ratio 1.55 (95% CI 1.07-2.25, one-sided P = 0.99). The 12-month disease-free survival rates were 47.1% and 64.0%, respectively. There were no toxicity concerns or excess early discontinuations. CONCLUSION: Nivolumab/ipilimumab did not improve disease-free survival compared with chemotherapy in patients with ypN+ and/or R1 gastro-oesophageal adenocarcinoma following neoadjuvant chemotherapy and surgery.
- MeSH
- adenokarcinom * patologie farmakoterapie terapie MeSH
- adjuvantní chemoterapie metody MeSH
- dospělí MeSH
- gastrektomie MeSH
- gastroezofageální junkce * patologie MeSH
- imunoterapie metody MeSH
- ipilimumab aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * patologie prevence a kontrola farmakoterapie epidemiologie MeSH
- nádory jícnu * patologie farmakoterapie terapie MeSH
- nádory žaludku * patologie farmakoterapie terapie chirurgie MeSH
- neoadjuvantní terapie * metody škodlivé účinky MeSH
- nivolumab aplikace a dávkování terapeutické užití MeSH
- přežití bez známek nemoci MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUNDS: SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. METHODS: Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. RESULTS: SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. CONCLUSIONS: In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.
- MeSH
- chromozomální proteiny, nehistonové * genetika metabolismus MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru patologie metabolismus genetika MeSH
- lymfatické metastázy MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prostaty rezistentní na kastraci patologie genetika metabolismus MeSH
- nádory prostaty * patologie metabolismus genetika MeSH
- prognóza MeSH
- senioři MeSH
- stupeň nádoru MeSH
- transkripční faktory genetika metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
The FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion-positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9-21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.
- MeSH
- dlaždicobuněčné karcinomy hlavy a krku virologie patologie genetika MeSH
- dospělí MeSH
- fenotyp MeSH
- fúzní onkogenní proteiny genetika MeSH
- infekce papilomavirem * patologie komplikace genetika virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory hlavy a krku * patologie virologie genetika MeSH
- proteiny asociované s mikrotubuly genetika MeSH
- receptor fibroblastových růstových faktorů, typ 3 * genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom patologie genetika virologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.
- MeSH
- adjuvantní chemoterapie MeSH
- adjuvantní radioterapie metody MeSH
- adrenalektomie * metody MeSH
- adrenokortikální karcinom * terapie farmakoterapie radioterapie MeSH
- adrenokortikální nádory * terapie farmakoterapie chirurgie radioterapie MeSH
- hormonální protinádorové látky * terapeutické užití MeSH
- lidé MeSH
- mitotan * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH