Current therapeutic approach to PGT includes surgery (as radical as possible) and radiotherapy [10, 11]. As already mentioned, PGT are a group of rare and extremely heterogeneous diseases. Prognosis of patients in terms of LC and survival outcomes depends on several clinical and pathological features and can be very different. It is then mandatory to identify features possibly simplifying the choice of the best treatment option for every patient.
In an historic paper by Theriault (1986) , 10 year recurrence-free survival rates were 62% and 22% respectively, in patients treated with surgery and in those treated with surgery + PORT. Cause-specific survival was independently related with these prognostic factors: histology, tumor stage, lymph node metastases, age and damage to the facial nerve. More recently, Chen et al. (2007)  reported that loco-regional recurrence rate for patients with high risk PGT receiving exclusive surgery could be as high as 63% in the subgroups of patients that presented at least one of the following characteristics: lymph-nodal metastases, high grade disease, stage T3-T4 disease, positive margins . The authors concluded that PORT should be carefully considered for patients with high risk PGT. Another paper by Mendenhall et al. (2005) reported that surgery + PORT induced better LC at multivariate analysis when compared with RT alone  in patients with high risk disease (defined as the presence of close or positive resection margins, high grade disease, lymph-nodal metastases, perineural or endothelial-lined space invasion).
Our data are consistent with those present in literature and confirm the importance of the prognostic factors mentioned before. In our series, 10-year LC was 67% for patients treated with surgery + PORT: pathological stage and DG were confirmed as independent predictors of loco-regional recurrence. Results in terms of survival outcomes were also comparable. Worst survival rates are in fact related with high grade and locally advanced disease. Both advanced T stage and nodal involvement impact negatively on survival. Multivariate analyses did not confirm HS as predictors of survival most likely due to the small numbers of patients in each subgroup. Nevertheless, survival outcomes of subgroups are consistent with current literature data .
In our series, 10-year MFS was 80%. Univariate analysis confirmed the worst MFS rates linked to the aggressive HS (SDC and NOS AC), to HG and to locally advanced disease. Furthermore, in our cases the presence of nodal disease resulted as the only predictor of MFS at multivariate analysis. Treatment strategies for patients diagnosed with distant metastases were also variable: chemotherapy (especially doxorubicin based), surgery, RT or a combination of treatments was preferred at clinician’s discretion. A wait-and-see strategy was chosen in two cases.
As expected, the time lapse from the first diagnosis to the time of appearance of metastases was extremely wide ranging from 1 month to almost 15 years (median time 17 months) and it well represents the different biological behaviors of different PGT. Similarly, CSS after the diagnosis of distant metastases was equally various and ranged from 0 to 73 months. Pattern of distant failures are presented in Fig. 3.
Given the recent extraordinary increase in the use of stereotactic ablative radiotherapy (SABR) in many different clinical settings, we reviewed the medical records of these patients to determine if, retrospectively, some of them could have benefitted from this approach. In fact, PGT are known for their relatively slow growing distant metastases and lungs, liver and bones are the most frequent sites of secondary spread (and this is confirmed in our series) . At least theoretically, this represents an optimal biological rationale for treating these patients with SABR because slow growing diseases are more sensitive to high doses per fraction  and contemporarily lungs, liver and bones are common sites of SABR for other primary or secondary tumors [20, 21, 22] in many radiation oncology departments. Moreover, recent data from the SABR-COMET [23, 24] by Palma and colleagues, although not including PGT in their trial, demonstrated a survival benefit in patients treated with SABR to oligometastases compared to palliative standard of care. In our series, only a few patients could have benefitted from SABR because in most cases the secondary spread was diagnosed at a relative late stage and therefore polimetastatic and the patients underwent chemotherapy (upfront or at further progression) with unsatisfying results.
Unfortunately, to date there are not enough data to sustain the hypothesis that some selected patients, if subjected to a more intensive follow up, could have had a survival benefit with SABR but in our opinion this approach should be further examined in the next future due to his strong biological rationale. Current international guidelines recommend life-long FU for all the patients treated for PGT and, maybe, for patients at high risk a more intensive radiological FU could determine a survival benefit.
No statistically significant correlation was found among PORT techniques, volumes or total dose and survival outcomes. To the best of our knowledge, also this is consistent with present literature data.
The most serious adverse event of PGT treatment is probably facial nerve paralysis which is often temporary but can sometimes be permanent (to our knowledge it is still unclear whether PORT could worsen the post-surgical recovery or not) . Other more or less common side effects of treatment included Frey’s syndrome (i.e. sweating and flushing in the preauricular area), xerostomia, trismus, dermatitis/fibrosis, dysgeusia, dysphagia, radiation-induced hearing impairment, bone necrosis [26, 27, 28]. In our series, radiation treatment courses were generally well tolerated. In fact, the only severe (≥ G3) toxicities reported were acute mucositis and dermatitis (20% and 9% respectively). PORT total dose only affected acute mucositis and acute/late xerostomia whereas no statistically significant correlation was found between PORT volumes or techniques and toxicities.
Of course, we are well aware of the main limitations of this study: first of all, the lack of a comparison group treated with surgery only; secondly, several surgical data, especially those belonging to patients treated in the early 90’s, were not available: more details regarding the surgical handling of the neck would be extremely interesting in a paper like this, as also concomitant chemotherapy indications and administration would. Yet, we think that this paper can still add some important information to the current literature about radiation therapy in parotid gland cancer, since it is, to our knowledge, one of the largest single Institution experience.