Mucosal melanoma (MucM) is a rare cancer with a poor prognosis and low response rate to immune checkpoint inhibition (ICI) compared with cutaneous melanoma (CM). To explore the immune microenvironment and potential drivers of MucM’s relative resistance to ICI drugs, we characterized 101 MucM tumors (43 head and neck [H&N], 31 female urogenital, 13 male urogenital, 11 anorectal, and 3 other gastrointestinal) using bulk RNA-Seq and immunofluorescence. RNA-Seq data show that MucM has a significantly lower IFN-γ signature levels than CM. MucM tumors of the H&N region show a significantly greater abundance of CD8 ⁺ T cells, cytotoxic cells, and higher IFN-γ signature levels than MucM from lower body sites. In the subcohort of 35 patients with MucM treated with ICI, hierarchical clustering reveals clusters with a high and low degree of immune infiltration, with a differential ICI response rate. Immune-associated gene sets were enriched in responders. Signatures associated with cancer-associated fibroblasts, macrophages, and TGF-β signaling may be higher in immune-infiltrated, but ICI-unresponsive tumors, suggesting a role for these resistance mechanisms in MucM. Our data show organ region–specific differences in immune infiltration and IFN-γ signature levels in MucM, with H&N MucM displaying the most favorable immune profile. Our study might offer a starting point for developing more personalized treatment strategies for this disease.

During a course of radiotherapy for head-and-neck-cancer (HNC), non-rigid anatomical changes can be observed on daily Cone Beam CT (CBCT). To objectify responses to these changes, we use a decision support system (traffic light protocol). Action levels orange and red may lead to re-planning. The purpose of this study was to evaluate how often re-planning was done for non-rigid anatomical changes, which anatomical changes led to re-planning and in which subgroups of patients treatment adaptation was deemed necessary. A consecutive series of 388 HNC patients were retrospectively selected using the digital log of CBCT scans. The logs were analyzed for the number of new plans on an original planning CT scan (O-pCT) or a new pCT scan (N-pCT). Reasons for re-planning were categorized into: target volume increase/decrease, body contour decrease/increase and local shift of target volume. Subgroup analysis was performed to investigate relative differences of re-planning between treatment modalities. For 33 patients the treatment plan was adapted due to anatomical changes, resulting in 37 new plans in total. Re-planning on a N-pCT with complete re-delineation was done 22 times. In fifteen cases a new plan was created after adjustment of contours on the O-pCT. Main reasons for re-planning were target volume increase, body contour decrease and local shifts of target volume. Most re-planning (23%) was seen in patients treated with chemoradiotherapy. Visual detection of anatomical changes on CBCT during treatment of HNC, results in re-planning in 1 out of 10 patients.

Background: To assess the prevalence of chronic lymphedema and trismus in patients > 6 months after head and neck cancer (HNC) treatment, and to explore how the severity of these conditions correlates with body image and quality of life. Methods: The cross-sectional sample included 59 patients, treated for HNC between six months to three years ago. Physical measurements were performed to assess the presence of external lymphedema and trismus (<36 mm). Furthermore, participants completed two questionnaires regarding body image (BIS) and quality of life (UW-QoL V4). Results: Lymphedema prevalence was 94.1% (95% CI 0.86–0.98), with a median severity score of 9 (range 0–24). Trismus prevalence in this sample was 1.2%. The median BIS score was 2, indicating a positive body image. The UW-QoL score showed a good QOL with a median of 100. Only the domain of saliva and overall related health had a lower median of 70 and 60, respectively. There was no correlation between lymphedema and body image (r = 0.08, p = 0.544). Patients with higher lymphedema scores reported poorer speech with a moderate correlation (r = −0.39, p = 0.003). Conclusion: Lymphedema is a highly prevalent, but moderately severe late side-effect of HNC with a limited impact on quality of life domains except for speech, in our cohort.