Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study
Authors: Leonardi Maria Cristina , Pepa Matteo , Gugliandolo Simone Giovanni , Luraschi Rosa , Vigorito Sabrina , Rojas Damaris Patricia , La Porta Maria Rosa , Cante Domenico , Petrucci Edoardo , Marino Lorenza , Borzì Giuseppina , Ippolito Edy , Marrocco Maristella , Huscher Alessandra , Chieregato Matteo , Argenone Angela , Iadanza Luciano , De Rose Fiorenza , Lobefalo Francesca , Cucciarelli Francesca , Valenti Marco , De Santis Maria Carmen , Cavallo Anna , Rossi Francesca , Russo Serenella , Prisco Agnese , Guernieri Marika , Guarnaccia Roberta , Malatesta Tiziana , Meaglia Ilaria , Liotta Marco , Tabarelli de Fatis Paola , Palumbo Isabella , Marcantonini Marta , Colangione Sarah Pia , Mezzenga Emilio , Falivene Sara , Mormile Maria , Ravo Vincenzo , Arrichiello Cecilia , Fozza Alessandra , Barbero Maria Paola , Ivaldi Giovanni Battista , Catalano Gianpiero , Vidali Cristiana , Aristei Cynthia , Giannitto Caterina , Miglietta Eleonora , Ciabattoni Antonella , Meattini Icro , Orecchia Roberto , Cattani Federica , Jereczek-Fossa Barbara Alicja 
Published: April 2021

Objectives:
To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV).

Methods:
The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them.

Results:
Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements.

Conclusions:
Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address.

Advances in knowledge
The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.