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ObjectivesTo assess the incidence and to review experience with the treatment of mucosal melanoma of the head and neck (MMHN) in Slovenia between 1985 and 2013.MethodsThe National Cancer Registry database and clinical records with outcome data of identified patients treated during the period 1985–2013 in Slovenia were reviewed.ResultsIn a 29-year period, 61 patients with MMHN were identified, representing 0.5 % of all head and neck malignant tumors and 42 % of all mucosal melanomas in Slovenia. 72 % originated in the sinonasal tract and were predominantly (78 %) diagnosed as a local disease. Regional metastases at diagnosis were more frequent in patients with oral/oropharyngeal primary (44 %; sinonasal MMHN 11 %, p = 0.006). Curative intent treatment was given to 48 (79 %) patients. The overall survival (OS) rates at 2 and 5 years for the whole cohort were 43 % and 18 %, respectively, and for the curative intent group 53 % and 24 %, respectively. In the latter group, multivariate analyses showed postoperative radiotherapy (PORT) to be predictive for locoregional control (LRC) (hazard ratios [HR] for surgery with PORT vs. surgery alone: 1.0 vs. 3.9, p = 0.037), whereas only the World Health Organization performance status (HR for grade 0 vs. grade 1 vs. grade >1: 1.0 (p = 0.022) vs. 1.2 (p = 0.640) vs. 7.7 (p = 0.008)) significantly influenced OS.ConclusionsMMHN is a rare tumor with a poor prognosis. Combination of surgery and PORT offers the best prospects for LRC but without improvement of OS. Due to potential toxicity of high-dose RT such treatment is indicated in patients in whom LRC outweighs the risks of serious adverse effects.

Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC.

BackgroundHead and neck squamous cell carcinoma (HNSCC) presents as locally advanced disease in a majority of patients and is prone to relapse despite aggressive treatment. Since immune checkpoint inhibitors (ICI) have shown clinically significant efficacy in patients with recurrent/metastatic HNSCC (R/M HNSCC), a plethora of trials are investigating their role in earlier stages of disease. At the same time, preclinical data showed the synergistic role of concurrently administered radiotherapy and ICIs (immunoradiotherapy) and explained several mechanisms behind it. Therefore, this approach is prospectively tested in a neoadjuvant, definitive, or adjuvant setting in non-R/M HNSCC patients. Due to the intricate relationship between host, immunotherapy, chemotherapy, and radiotherapy, each of these approaches has its advantages and disadvantages. In this narrative review we present the biological background of immunoradiotherapy, as well as a rationale for, and possible flaws of, each treatment approach, and provide readers with a critical summary of completed and ongoing trials.ConclusionsWhile immunotherapy with ICIs has already become a standard part of treatment in patients with R/M HNSCC, its efficacy in a non-R/M HNSCC setting is still the subject of extensive clinical testing. Irradiation can overcome some of the cancer’s immune evasive manoeuvres and can lead to a synergistic effect with ICIs, with possible additional benefits of concurrent platinum-based chemotherapy. However, the efficacy of this combination is not robust and details in trial design and treatment delivery seem to be of unprecedented importance.

In patients with squamous cell carcinoma (SCC) metastases to neck lymph nodes and unknown primary tumor, the role of elective irradiation of uninvolved neck and potential mucosal primary sites is yet to be determined. The aim of this study was to review the experience treating SCC of unknown primary metastatic to neck nodes with surgery and postoperative radiotherapy (PORT) in Slovenia between 1995 and 2010 and to determine the importance of the extent of irradiated volume. For this purpose, the nationwide Cancer Registry of Slovenia database was used for identifying patients. 126 patients were identified. Involved-field PORT and extended-field PORT was used in 50 and 76 patients, respectively. At 5 years, locoregional control was 86 %, disease-specific survival 77 %, and overall survival 57 %. In multivariate analysis, the extent of irradiated volume has not been predictive for any outcome under study. Grade ≥3 acute and late radiotherapy-induced toxicities were more frequent in the extended-field PORT group. In conclusion, although not superior, involved-field PORT seems to be a preferred treatment option in SCC of unknown primary metastatic to neck nodes due to significantly reduced toxicity and better prospects for successful salvage.

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In the current study, we sought to compare survival outcomes after breast-conserving therapy (BCT) or mastectomy alone in patients with stage I-IIA breast cancer, whose tumors are typically suitable for both locoregional treatments. The study cohort consisted of 1360 patients with stage I-IIA (T1–2N0 or T0–1N1) breast cancer diagnosed between 2001 and 2013 and treated with either BCT (n = 1021, 75.1%) or mastectomy alone (n = 339, 24.9%). Median follow-ups for disease-free survival (DFS) and overall survival (OS) were 6.9 years (range, 0.3–15.9) and 7.5 years (range, 0.2–25.9), respectively. Fifteen (1.1%), 14 (1.0%) and 48 (3.5%) patients experienced local, regional, and distant relapse, respectively. For the whole cohort of patients, the estimated 5-year DFS and OS were 96% and 97%, respectively. After stratification based on the type of local treatment, the estimated 5-year DFS for BCT was 97%, while it was 91% (p < 0.001) for mastectomy-only treatment. Inverse probability of treatment weighting matching based on confounding confirmed that mastectomy was associated with worse DFS (HR 2.839, 95% CI 1.760–4.579, p < 0.0001), but not with OS (HR 1.455, 95% CI 0.844–2.511, p = 0.177). In our study, BCT was shown to have improved disease-specific outcomes compared to mastectomy alone, emphasizing the important role of adjuvant treatments, including postoperative radiation therapy, in patients with early-stage breast cancer at diagnosis.

Purpose To determine whether muscle mass, defined by fat-free mass index (FFMI) measured with bioelectrical impedance analysis (BIA), is predictive of survival of head and neck squamous cell carcinoma (HNSCC) patients. Methods HNSCC patients treated between 2014 and 2018 at the Department for Nutrition of the Institute of Oncology Ljubljana were reviewed. The FFMI values from the pretreatment BIA measurements and pretreatment body mass index (BMI) were used to categorize patients into groups with low and normal muscle mass and BMI using the Global Leadership Initiative on malnutrition (GLIM) recommended cutoff values. The impact of FFMI on disease-free survival (DFS) and overall survival (OS) was determined. Results Of the 71 included patients, 31 (43.7%) had normal FFMI, and 40 (56.3%) had low FFMI, whereas 44 (62%) and 27 (38%) of the patients had normal and low BMI, respectively. Between FFMI and BMI values, a significant correlation was found (RP = 0.75, p < 0.001). Univariate regression analysis showed that FFMI (as a continuous variable) was of prognostic significance for OS (p = 0.039), which was confirmed by multivariate regression analysis (p = 0.029). The model where BMI replaced FFMI negated the prognostic value of BMI (as a continuous variable). Neither FFMI nor BMI was found to be a predictor of DFS on univariate or multivariate analysis. Conclusions In the present group of HNSCC patients, low FFMI adversely influenced OS, emphasizing the importance of using body composition measurement over BMI alone for pretreatment nutritional evaluation of these patients.