Desmoid tumors display a strong immune infiltration at the tumor margins and no PD-L1-driven immune suppression

Characterization of the tumor immune microenvironment (TME) and immune checkpoints can possibly help identify new immunotherapeutic targets for Desmoid tumors (DTs). We performed immunohistochemistry (IHC) on 33 formalin-fixed paraffin-embedded (FFPE) tissue sections from DT samples to characterize the TME and the immune checkpoint expression profile. We stained for CD3, CD4, CD8, CD20, FoxP3, CD45RO, CD56, CD68, NKp46, granzyme B, CD27, CD70, PD1 and PD-L1. We found that most of the tumors showed organization of lymphocytes into lymphoid aggregates at the periphery of the tumor, strongly resembling tertiary lymphoid organs (TLOs). The tumor expressed a significant number of memory T cells, both at the periphery and in the tumoral stroma. In the lymphoid aggregates, we also recognized a significant proportion of regulatory T cells. The immune checkpoint ligand PD-L1 was negative on the tumor cells in almost all samples. On the other hand, PD1 was partially expressed in lymphocytes at the periphery of the tumor. To conclude, we are the first to show that DTs display a strong immune infiltration at the tumor margins, with formation of lymphoid aggregates. Moreover, we demonstrated that there is no PD-L1-driven immune suppression present in the tumor cells.

Our aim was to examine the outcome of radiotherapy (RT) in the treatment of primary or recurrent unresectable desmoid tumors of the neck. A retrospective analysis was performed on 30 patients between 1/2008 and 12/2017, with 3 primary and 27 recurrent unresectable desmoid tumors of the neck. All cases were reviewed by pathologists. The median follow-up time was 50.5?months (range 2-126?months). Radiotherapy doses varied from 50 to 66?Gy (median 60?Gy, 23/30 patients) with all fraction size of 2?Gy. The objective response rate (ORR: CR or PR) to definitive RT was 56.7% (17/30 patients). On Chi-square statistic, ORR was significantly influenced by tumor size (?5?cm versus >5?cm) (p?=?.046). The most common acute side effects of the radiation-related complication were grade 1-2 skin toxicities. Radiotherapy is a valuable option in the management of primary or recurrent unresectable DTs of the neck with good local control. Multi-institutional and prospective studies are warranted to further validate our findings.

Sarcoma is a broad term for mesenchymal malignancies that arise from soft tissue or bone. Despite classification by histologic subtype, clinical behavior and response to therapy have great variability. Modern genetic sequencing techniques have been able to identify additional genetic variability and subsequently new targeted therapies. In this review, we discuss the current state of STS diagnostics and treatment and explore some of the more promising areas in which progress is being made. We discuss therapies targeting PDGFRalpha/KIT, beta-Catenin/APC/NOTCH, IDH-1/2 mutations, MDM2 amplifications, EZH2/INI1 expression loss, ALK fusion, and ASPSCR1-TFE3 fusion. We also discuss the progress that has been made within immunotherapies. While soft tissue sarcomas still portend a poor prognosis, these targeted therapies and immunotherapies provide treatment with less toxic side effects.

We report our experience of cryoablation as a local and analgesic treatment for inoperable or recurring desmoid tumors. This study includes 34 patients who underwent percutaneous cryoablation of 41 desmoid tumors between July 2012 and September 2016. All patients underwent pain assessment using a visual analog scale (VAS) and preoperative imaging. All cryoablation procedures were performed using the same cryoablation system. Patients received clinical and radiological follow-up at 6 months post-procedure, with pain-rating and adverse events being recorded. A long-term follow-up was achieved until 31 December 2018. Radiological tumor response was determined by tumor measurements using RECIST 1.1. Twelve patients benefitted from curative treatment on 100% of the tumor volume, but 22 patients received debulking treatment because of the risk of neighboring structures. Two patients had a postoperative hematoma grade 2 of the CIRSE classification system for complications, and two patients had grade 4 complications involving palsy of the common fibular nerve. Disease-free survival at 3 years was 42.2%. The mean VAS pain scores were 5.7 and 2.4 at pretreatment and 6 months, respectively, showing a mean reduction of 3.3 (p?<?0.001). At 6 months, all measured tumor dimensions were significantly lower than pretreatment. Cryoablation is an effective therapeutic option for the local treatment and for the analgesic management of desmoid tumors.

We retrospectively reviewed 296 MRI studies of 34 patients with histologically proven desmoid-type fibromatosis (DF). In each study, tumor volume and T2 signal relatively normal striated muscle were assessed. Volume variation and monthly growth rates were analyzed to determine lesion growth behavior (progressing vs stable/regressing lesions). Growth behavior was correlated with T2 signal, tumor location, beta-catenin status, treatment strategy, and follow-up duration. There were 25 women and 9 men with a mean age of 39.9?±?19 (4-73) years. Mean follow-up time in the patients included was 55?±?41 (12-148) months. In progressing lesions, the mean average monthly growth ratio was 10.9?±?9.2 (1.1-42.5) %. Interobserver variability of volume measurements was excellent (ICC?=?0.96). Mean interobserver measurement variation ratio was 20.4?±?23.6%. The only factor correlated with tumor growth behavior was T2 signal ratio (p <?0.0001). Seventeen out of 34 (50%) patients presented a signal change over the threshold of 1 during follow-up. There were five occurrences of secondary growth after a period of stability with a mean delay until growth of 38.2?±?44.2 (17-116) months. DF growth rate was quantitatively assessed. A threshold for volume variation detection was established. DF growth behavior was significantly related to T2 signal. An evidence-based follow-up strategy is proposed.

This study aimed to determine the clinical significance of MRI characteristics as a possible predictor of responsiveness to meloxicam treatment in patients with desmoid-type fibromatosis (DF). Additionally, it analysed the correlation between CTNNB1 mutation status and signal intensity of MRI. Forty-six patients consecutively treated with meloxicam composed this study. The low-intensity area (LIA) on T2-weighted MRI was determined. We divided patients into two groups based on the efficacy of meloxicam: a clinical benefit group (CB group, including CR: complete response; PR: partial response; and SD: stable disease) and non-clinical benefit group (NB group, including PD: progressive disease). In total, 11, 17 and 18 patients showed PR, SD and PD, respectively. The mean LIA ratio before treatment was significantly higher (P < 0.001) in the CB group than in the NB group. For predicting the efficacy, sensitivity was 68%, and specificity was 89% when setting the cut-off value as 20% for LIA. Mean changes in the LIA ratio before and after treatment were significantly higher (P = 0.01) in the CB group than in the NB group. Mean LIA ratio before treatment was significantly lower (P < 0.001) in the S45F mutation group than in the other mutation group. In multivariate analysis, the LIA ratio before treatment was a significant predictor of responsiveness (P = 0.02). MRI characteristics were a useful predictor of the efficacy of meloxicam in DF patients. It may be possible to predict the clinical outcome more accurately when combined with other factors, such as CTNNB1 mutantion status.