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Additional file 1: Supplementary Table 1. Generalizability sample of pathology data extracted from pathology reports compared to initial cohort. A). Basic clinical characteristics of patients for each year of the sample used in this paper (n = 1502). These are the 3656 patients of which 44% of each year pathology data were extracted and CIS were removed. B). Basic clinical characteristics of the total dataset of patients for each year (n = 3380). These are the 3656 patients with reliable linkage between NKR-PALGA minus 276 CIS patients leaving 3380 patients in total. Supplementary Table 2. Histological characteristics, locoregional recurrences and death of patients treated with tumor-positive lymph nodes (n = 205). Supplementary Table 3. Histological characteristics, locoregional recurrences and death of T3/T4 N0/N+ patients treated with TLE or TLE with RT (n = 98). Supplementary Figure 1. Separate multivariable analysis of extracapsular spread, keratinization and PNI+/VI+/Growth pattern. Each separate histological characteristic was corrected for age, gender, sublocalisation and stage/treatment for locoregional recurrence and death of patients with positive lymph nodes (n = 205). Supplementary Figure 2. Univariable analysis of histological characteristics of the primary tumor for locoregional recurrence and death of T3/T4 N0/N+ patients treated with TLE or TLE with RT (n = 98). * p

Additional file 1: Supplementary Figure 1. Differences in PSMA expression between primary, recurrent and metastatic AdCC in 18 patients, in order of PSMA expression of the primary tumour.

Background: Validation of magnetic resonance imaging (MRI) and development of guidelines for the delineation of the gross tumor volume (GTV) is of utmost importance to benefit from the visibility of anatomical details on MR images and to achieve an accurate GTV delineation. In the ideal situation, the GTV delineation corresponds to the histopathologically determined ‘true tumor volume’. Consequently, we developed guidelines for GTV delineation of laryngeal and hypopharyngeal tumors on MRI and determined the accuracy of the resulting delineation of the tumor outline on histopathology as gold standard. Material and methods: Twenty-seven patients with T3 or T4 laryngeal/hypopharyngeal cancer underwent a MRI scan before laryngectomy. Hematoxylin and eosin sections were obtained from surgical specimens and tumor was delineated by one pathologist. GTV was delineated on MR images by three independent observers in two sessions. The first session (del1) was performed according to clinical practice. In the second session (del2) guidelines were used. The reconstructed specimen was registered to the MR images for comparison of the delineated GTVs to the tumor on histopathology. Volumes and overlap parameters were analyzed. A target margin needed to assure tumor coverage was determined. Results: The median GTVs (del1: 19.4 cm3, del2: 15.8 cm3) were larger than the tumor volume on pathology (10.5 cm3). Comparable target margins were needed for both delineation sessions to assure tumor coverage. By adding these margins to the GTVs, the target volumes for del1 (median: 81.3 cm3) were significantly larger than for del2 (median: 64.2 cm3) (p ≤ 0.0001) with similar tumor coverage. Conclusions: In clinical radiotherapy practice, the delineated GTV on MRI is twice as large as the tumor volume. Validated delineation guidelines lead to a significant decrease in the overestimation of the tumor volume.