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Radiotherapeutic management of cervical lymph node metastases from an unknown primary site - experiences from a large cohort treated with modern radiation techniques.

ABSTRACT: PURPOSE:To analyze management and outcomes following (chemo)radiation therapy in patients with cervical lymph node metastases from an unknown primary site (CCUP) in a large single-center cohort. METHODS:Between 2008 and 2019, 58 patients with CCUP were treated with (chemo)radiation therapy at the University of Freiburg Medical Center and were included in this analysis. Overall survival (OS), locoregional progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The use of diagnostic procedures and their impact on oncological outcomes was analyzed by Cox regression, and treatment-related toxicities were quantified. RESULTS:Median follow-up was 29.9?months (range 4.6-121.9). Twenty-one patients (36.2%) received definitive RT, 35 (60.3%) underwent adjuvant RT, and 2 (3.4%) were treated for oligometastatic disease. Concurrent chemotherapy was prescribed in 40 patients (69.0%). 89.6% of patients completed the prescribed RT, and 65.0% completed the prescribed simultaneous chemotherapy. Locoregional recurrence was observed in 7 patients (12.1%) and distant metastases in 13 cases (22.4%). OS was 81,1, 64.9% and 56,6% after 1, 3 and 5?years, respectively. Univariate analysis of age, gender, extracapsular spread, tumor grading, neck dissection, diagnostic utilization of 18F-fluorodeoxyglucose positron-emission tomography and concomitant chemotherapy showed no effect on OS (p?>?0.05 for all), while smoking was significantly associated with decreased survival (p?

SUBMITTER: Sprave T

PROVIDER: S-EPMC7158130 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Radiotherapeutic management of cervical lymph node metastases from an unknown primary site - experiences from a large cohort treated with modern radiation techniques.

Sprave Tanja T Rühle Alexander A Hees Katharina K Kalckreuth Tobias T Verma Vivek V Stoian Raluca R Zamboglou Constantinos C Pfeiffer Jens J Laszig Roland R Knopf Andreas A Grosu Anca-Ligia AL Nicolay Nils H NH

Radiation oncology (London, England) 20200415 1

<h4>Purpose</h4>To analyze management and outcomes following (chemo)radiation therapy in patients with cervical lymph node metastases from an unknown primary site (CCUP) in a large single-center cohort.<h4>Methods</h4>Between 2008 and 2019, 58 patients with CCUP were treated with (chemo)radiation therapy at the University of Freiburg Medical Center and were included in this analysis. Overall survival (OS), locoregional progression-free survival (PFS) and distant metastasis-free survival (DMFS) w ...[more]

PMID: 32293497

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Project description:BackgroundPatients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).MethodsGenomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.FindingsThe downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.InterpretationSingle lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.FundingThis work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).

Project description:BackgroundUnlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection.MethodsWe selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma.ResultsOne hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56).ConclusionPediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.

Dataset Information

Radiotherapeutic management of cervical lymph node metastases from an unknown primary site - experiences from a large cohort treated with modern radiation techniques.

Publications

Radiotherapeutic management of cervical lymph node metastases from an unknown primary site - experiences from a large cohort treated with modern radiation techniques.

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