Eduardo Netto

Liver metastases from soft tissue sarcoma (STS) (excluding gastrointestinal stromal tumors) are rare and more commonly arise from retroperitoneal and intra-abdominal primary sites. Chemotherapy remains the mainstay of treatment for disseminated disease, but its effectiveness is limited and patients typically have a dismal prognosis with short survival. However, when metastases are confined to the liver (without pulmonary involvement), some patients may benefit from local techniques, either surgical or nonsurgical, that can provide long periods of disease-free survival. Due to the rarity of STS, especially with liver metastases, and the heterogeneity of histologies and biological behavior, there is a lack of standardized treatment guidelines and universally accepted criteria for this specific setting. To fill this gap, a multidisciplinary working group of experts in sarcoma and liver surgery reviewed the literature and available evidence and developed a set of clinical recommendations to be voted and discussed in the I Ibero-American Consensus on the Management of Metastatic Sarcoma, held at the III Spanish-Portuguese Update Meeting on the Treatment of Sarcomas in May 2024. Herein, the voting results of this meeting and the resulting consensus recommendations are presented, and their applicability, strengths, and limitations are discussed.

Aim: Report our results of biomarker discovery in formalin-fixed paraffin-embedded (FFPE) nasopharyngeal carcinoma (NPC) via proteomic analysis. Background: Nasopharyngeal carcinoma (NPC) is a rare cancer in Western countries. Proteomic analysis have already been reported as a useful tool to provide biomarkers. Formalin-fixed paraffin-embedded (FFPE) samples, despite largely underused, can provide invaluable information for biomarker research via proteomic analysis. Methods: FFPE samples of NPC were submitted to protein extraction followed by FASP-digestion and label-free quantitative mass spectrometry (MS). Patients’ received concurrent chemoradiation with or without adjuvant chemotherapy as per Intergroup 0099 trial. IMRT was delivered following the RTOG0615 specifications. Toxicity was scored using the CTCAE 4.03 tables. Survival was estimated using Kaplan–Meier curves. Log-rank was used to detect differences. KEGG ontology graphics were generated. Results: 28 FFPE samples from NPC patients were used. Patients were: 79% male, 97% Caucasians, 86% WHO type 3, 40% T1, 10% T2, 25% T3, and 25% T4. With a median follow up of 37 months, local control was 83 (T1, 100% T2, T3 and T4), overall survival was 84%, and six patients developed distant metastases. All five patients that died were due to metastatic disease. Tumor samples contained a median of 75% of tumor material. We found Epstein–Barr (EBV) and Herpes simplex (HSV) viruses’ related proteins significantly present in early-stage primary NPC (T1 and T2, p < 0.01). A pool of 10 proteins was statistically up-regulated in the metastatic group of patients (p < 0.01). Median survival from this M1 group was p < 0.001). Conclusions: FFPE samples yielded adequate material for MS analysis. We found EBV and HSV related proteins on early-stage NPC, and proteomic profiling associated with distant metastases, potential candidates of disease biomarkers. Validation is needed.

Purpose: Report our matured outcomes of European nasopharyngeal carcinoma (NPC) treatment from a non-endemic region in the IMRT era. Methods: We reviewed 109 consecutive patients with biopsy proven NPC treated between 2009 and 2013. All received IMRT as per RTOG 0615. Toxicity was scored accordingly to CTCAE 4.03. Platinum-based chemotherapy was delivered following the Intergroup 0099. Results: Median age of 53 years; 97% Caucasian; 74% male; 72% WHO grade III; 43% Tl; 14% T2; 18% T3, 25% T4; 17% NO; 17% N1; 39% N2; 27% N3. Compliance to adjuvant chemotherapy was 88%. With a median follow up of 56 months, the 4-year local control was 90.2% (88.6% for Tl; 100% for T2; 85% for T3; and 91.7% for T4), the 4-year distant metastases-free survival was 86% and an overall survival rate was 77%. Local control and survival were better in G3 (p < 0.001 and p = 0.032, respectively). Xerostomia was the most frequent late toxicity in 55% (n = 60). Hypothyroidism requiring hormonal reposition occurred in 15.5% (n = 17). From the 36 deaths, 20 were due to distant metastases, 3 grade 5 toxicity, 2 from local progression, 5 non-cancer deaths and unknown cause in the remaining 6. On multivariable analysis, age (p = 0.017), local recurrence and distant metastases were associated with death (p <0.001, both). Conclusion: Our matured data from the IMRT era showed a major improvement from our 3D cohort series reaching excellent local and regional control, even in T4. Local recurrences, despite few, and distant metastases were correlated with the risk of death. (C) 2020 Greater Poland Cancer Centre. Published by Elsevier B.V. All rights reserved.

Background: This work aims at clinically validating a graphical tool developed for treatment plan assessment, named SPIDERplan, by comparing the plan choices based on its scoring with the radiation oncologists (RO) clinical preferences. Methods: SPIDERplan validation was performed for nasopharynx pathology in two steps. In the first step, three ROs from three Portuguese radiotherapy departments were asked to blindly evaluate and rank the dose distributions of twenty pairs of treatment plans. For plan ranking, the best plan from each pair was selected. For plan evaluation, the qualitative classification of ‘Good’, ‘Admissible with minor deviations’ and ‘Not Admissible’ were assigned to each plan. In the second step, SPIDERplan was applied to the same twenty patient cases. The tool was configured for two sets of structures groups: the local clinical set and the groups of structures suggested in international guidelines for nasopharynx cancer. Group weights, quantifying the importance of each group and incorporated in SPIDERplan, were defined according to RO clinical preferences and determined automatically by applying a mixed linear programming model for implicit elicitation of preferences. Intra- and inter-rater ROs plan selection and evaluation were assessed using Brennan-Prediger kappa coefficient. Results: Two-thirds of the plans were qualitatively evaluated by the ROs as ‘Good’. Concerning intra- and inter-rater variabilities of plan selection, fair agreements were obtained for most of the ROs. For plan evaluation, substantial agreements were verified in most cases. The choice of the best plan made by SPIDERplan was identical for all sets of groups and, in most cases, agreed with RO plan selection. Differences between RO choice and SPIDERplan analysis only occurred in cases for which the score differences between the plans was very low. A score difference threshold of 0.005 was defined as the value below which two plans are considered of equivalent quality. Conclusion: Generally, SPIDERplan response successfully reproduced the ROs plan selection. SPIDERplan assessment performance can represent clinical preferences based either on manual or automatic group weight assignment. For nasopharynx cases, SPIDERplan was robust in terms of the definitions of structure groups, being able to support different configurations without losing accuracy.

Background: ACCHN is a rare entity mainly found in the major and minor salivary glands. Localized disease is frequent and very late recurrences are common. The treatment of choice is surgery, when feasible, followed by radiotherapy (RT). RT alone is used in unresectable [RC1] patients (pts).