Dataset Information

Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis.

ABSTRACT: This meta-analysis was designed to evaluate radiotherapy (RT) options preferable for neck cancer metastases from unknown primary sites (NCUP). Relevant articles published up through September 2015 were selected from EMBASE, Cochrane, PubMed and Web of Science. Thirty-three articles were identified, and relative risks (RRs) and 95% CIs for all pre-specified endpoints were calculated. Surgery plus RT showed an advantage for 5-year overall survival (OS) (RR 0.66, 95% CI 0.52-0.83, p = 0.0004) and neck recurrence (NR) (RR = 0.74, 95% CI 0.59-0.92, p = 0.008) compared to RT alone. The RRs for NR, primary tumor emergence (PTE), and 5-year disease free survival (DFS) for bilateral neck compared to ipsilateral neck irradiation were 0.61 (95% CI 0.41-0.91, p = 0.01), 0.44(95% CI 0.26-0.77, p = 0.004), and 0.81 (95% CI 0.64-1.03, p = 0.09), respectively. Irradiation of the neck plus potential primary tumor sites (PPTS) showed a benefit for 5-year DFS (RR 0.75, 95% CI 0.61-0.92, p = 0.005), NR (RR = 0.72, 95% CI 0.56-0.92, p = 0.009), and PTE (RR = 0.23, 95% CI 0.12-0.45, p < 0.0001) compared to neck-only irradiation. Adverse events occurred more frequently with bilateral neck plus PPTS irradiation. For NCUP, surgery plus RT of the bilateral neck and PPTS was associated with greater improvement of clinical outcomes.

SUBMITTER: Liu X

PROVIDER: S-EPMC5346673 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis.

Liu Xiaomei X Li Dianhe D Li Na N Zhu Xiaoxia X

Oncotarget 20161101 48

This meta-analysis was designed to evaluate radiotherapy (RT) options preferable for neck cancer metastases from unknown primary sites (NCUP). Relevant articles published up through September 2015 were selected from EMBASE, Cochrane, PubMed and Web of Science. Thirty-three articles were identified, and relative risks (RRs) and 95% CIs for all pre-specified endpoints were calculated. Surgery plus RT showed an advantage for 5-year overall survival (OS) (RR 0.66, 95% CI 0.52-0.83, p = 0.0004) and n ...[more]

PMID: 27791201

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Project description:Carcinoma of unknown primary (CUP) is a difficult-to-manage malignancy. Multi-omic profiles and treatment outcome vs. degree of precision matching were assessed. Tumours underwent next-generation sequencing (NGS) [tissue and/or blood-derived cell-free DNA (cfDNA)]. Selected patients had transcriptome-based immune profiling and/or programmed cell death 1 ligand 1 (PD-L1) immunohistochemistry analysis. Patients could be reviewed by a Molecular Tumor Board, but physicians chose the therapy. Of 6497 patients in the precision database, 97 had CUP. The median number of pathogenic tissue genomic alterations was 4 (range, 0-25), and for cfDNA, was 2 (range, 0-9). Each patient had a distinct molecular landscape. Food and Drug Administration (FDA)-approved biomarkers included the following: PD-L1+ ≥ 1%, 30.9% of CUPs tested; microsatellite instability, 3.6%; tumour mutational burden ≥ 10 mutations·Mb-1, 23%; and neurotrophic receptor tyrosine kinase (NTRK) fusions, 0%. RNA-based immunograms showed theoretically druggable targets: lymphocyte activation gene 3 protein (LAG-3), macrophage colony-stimulating factor 1 receptor (CSF1R), adenosine receptor A2 (ADORA2) and indoleamine 2,3-dioxygenase 1 (IDO1). Overall, 56% of patients had ≥ 1 actionable biomarker (OncoKB database). To quantify the degree of matching (tumours to drugs), a Matching Score (MS; roughly equivalent to number of alterations targeted/total number of deleterious alterations) was calculated post hoc. Comparing evaluable treated patients [MS high, > 50% (N = 15) vs. low ≤ 50% (N = 47)], median progression-free survival was 10.4 vs. 2.8 months (95% CI 0.11-0.64; HR 0.27; P = 0.002); survival, 15.8 vs. 6.9 months (95% CI 0.17-1.16; HR 0.45; P = 0.09); and clinical benefit rate (stable disease ≥ 6 months/partial/complete response), 71% vs. 24% (P = 0.003). Higher MS was the only factor that predicted improvement in outcome variables after multivariate analysis. In conclusion, CUPs are molecularly complex. Treatments with high degrees of matching to molecular alterations (generally achieved by individualized combinations) correlated with improved outcomes.

Project description:IntroductionStereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT.MethodsA systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the I2 statistic and Cochran Qtest. Forest plots were generated for each endpoint.ResultsFifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported.ConclusionsSBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.

Dataset Information

Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis.

Publications

Optimization of radiotherapy for neck carcinoma metastasis from unknown primary sites: a meta-analysis.

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