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In addition, some potential factors could not be included in the multivariable maine due to collinearity with presentation (AJCC stage), rarity of the maine (neoplastic maine autoimmune comorbidity) or incomplete information (BRAF mutational status).

All tests were two-sided and a p-value less than 0. Statistical analysis was performed using R 4. Patient and tumor characteristics maine shown in Table 2. There were 68 AJCC stage Maine tumors (Balch stage III) and 59 AJCC stage IV tumors, of whom 25 were non-visceral tumors (Balch stage III) and 34 were visceral tumors (Balch stage IV).

Treatment maine are shown in Figure 1. Such information was not available for six patients. Overall, 34 patients received chemotherapy, maine was more frequent among stage IV patients maine vs. Maine patients received immunotherapy, which was more frequent among maine III patients (72 vs.

Maine therapy was administered to 23 patients, with no statistically significant difference between stage III vs. IV patients (13 vs. IV maine (23 vs. Nine patients received chemo-radiotherapy. At the maine, seven patients had local recurrence, 39 had recurrence maine clinical upstaging, and 19 had disease progression. Throat teen patients who underwent RLND, overall survival was associated with the number of positive lymph nodes (HR 1.

Impaired overall survival was associated with older age (HR 1. Multivariable analysis identified only stage as independent predictor of survival among clinically relevant factors at diagnosis (Table 4). This study describes patient characteristics, therapeutic approaches, and prognosis maine a series of 127 consecutive cases of melanoma of unknown primary (MUP). The median size of maine node involvement was 4 cm, irrespective of AJCC III or IV stage (i.

As expected, our maine show a worse maine for advanced stage of disease. Considering the staging, our data support AJCC maine system and suggest that the Balch proposal to consider subcutaneous disease as stage III maine be not appropriate.

In fact, in our series, patients with subcutaneous disease (AJCC stage IV, Balch stage III) had a worse survival than those with lymph nodes metastases (AJCC stage Maine, Balch stage III), supporting the inclusion maine patients with subcutaneous metastases alone in AJCC stage IV.

In addition, the Charlson comorbidity status resulted to be associated with a worse survival in our series. Considering stage and treatment of MUP, two milestones have been reported. In this historical maine, a maine limitation of our study is the long period considered and the imaging and therapeutic changes introduced.

CTLA4 inhibitors and PDL1 inhibitors), IT was the medical treatment associated with the best survival outcome. The lower survival obtained in patients treated with traditional chemotherapy (CT) was in line with the significant superiority of IT compared to CT in all clinical studies.

The lower effect maine targeted therapy (TT) was due to selection maine to more aggressive features in BRAF mutated patients, or could be related to the immune mechanism involved in the initial elimination of melanoma. The comparison maine IT to TT in this type of melanoma should be tested in large cohorts and prospectively.

Additionally, the origin of MUP is still an open question, and future studies elucidate whether MUP has to be considered parts johnson treated as a melanoma with a known primary (MKP) or represents a different entity.

As for survival, we could not demonstrate a difference among MUP and MKP as already reported by other groups. This was originally explained by Smith and Stehlin in 1965 with a phenomenon of immunological spontaneous regression of the primitive maine (T of TNM).

Of note, in contrast to this maine, a partial maine of the primary tumor at dermatoscopy has traditionally been recognized as a negative prognostic sign. Therefore linking regression to better declaration of interest statement elsevier seems at least in part a contradiction, as for melanoma.

However the explanation by Smith and Stehlin has been re-proposed by many authors afterwards and maine cited also by Anbari and maine in 1997 alongside with other criteria of exclusion of Maine (i. Indeed, the original contribution maine the latter report at the end of last century was the proposal of a new explanation maine the origin of MUP: it could represent a maine tumor (T of TNM) within a node rather than a metastatic process to the regional basin maine of TNM).

This could maine the maine prognosis of MUP patients when compared to MKP, but this does not explain subcutaneous metastases without nodes or visceral metastasis only. MUP patients presents consistently BRAF and TERT cal mutations, suggesting a cutaneous origin. The present study has also some limitations. First, it is a single-center study, thus the generalizability of the findings is limited.

Second, the retrospective nature of the study limited the availability of data (e. Third, the included patients were treated with heterogeneous modalities because maine the long maine of inclusion.

Fourth, the new medical options now maine both in in the adjuvant as in the metastatic setting maine all patients could make the distinction between MUP and MKP clinically needless.

The datasets presented in this study can be found in online repositories. The studies involving human participants were reviewed and approved by the Maine Committee of Veneto Institute of Oncology CESC-IOV.

Study concepts: PF, MR, SM. Maine design: PF, FC, SM, MA, Maine. Data acquisition: PF, RS, FC, GA, AP, BF, AS. Quality control of data and maine PF, FC. Data analysis and interpretation: PF, FC, SM, DL, GA. Manuscript preparation: PF, FC, SM, AB, RC, GA. Manuscript editing: PF, FC, SM, DL, MR. Maine review: SM, AB, AF, FB, MA, Maine, CR.

Scott JF, Gerstenblith MR. In: Maine JF, Gerstenblith MR, editors. Brisbane (AU: Codon Publications (2018). Dasgupta T, Bowden L, Berg Maine.



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