Despite the tremendous gains achieved with the introduction of highly-conformal radiation techniques such as IMRT, considerable proportion of HNSCC patients still experience troublesome acute and late side-effects like dysphagia and xerostomia. As a consequence of improved prognosis and the increased incidence of oropharyngeal cancer among young (HPV+) patients, these patients will live longer with the burden of permanent radiation sequelae and the consequential deterioration of quality of life (QOL). Therefore, improving toxicity profiles and QOL after treatment become increasingly important. Different ongoing studies are now investigating different strategies to de-escalate the (radiation)treatment in these patients in order to reduce the radiation-related acute and late toxicities and improve QOL in these patients.
In my presentation, I will try to summarize the almost countless strategies targeting acute and late radiation-related toxicity in HNSCC, broadly dividing them into 3 categories; reducing the intensity of (chemo)radiation, reducing the irradiated volume, and by directly targeting the devil (the tumor). Subsequently, I will focus the rest of my presentation on the work we are doing at the Netherlands Cancer Institute regarding the elective nodal irradiation and the reduced radiation margins resulting in significant reduction of the irradiated volumes.
Because of the rich lymphatic network in the head and neck region the great majority of HNSCC received bilateral elective nodal irradiation (ENI). This might mean an overtreatment in the majority of these patients. This is the reason why we initiated two studies where the ENI is tailored by the presence or absence of the lymphatic drainage to the contralateral neck using SPECT, and when there is contralateral uptake of Tc99m, sentinel node procedure will be performed to exclude contralateral metastasis. In this case, unilateral ENI will be given. Compared to the matched bilateral ENI group, patients treated with SPECT/CT-guided ENI had significantly lower incidences of grade ≥2 dysphagia (54% vs. 82%; p <0.001), feeding tube (10% vs. 50%; p <0.001) and late grade ≥2 xerostomia (9% vs. 54%; p <0.001). Significant and clinically relevant HRQOL benefits of SPECT/CT-guided ENI were observed on the EORTC QLQ-C30 summary score, and QLQ-HN35 swallowing and dry mouth subscales. In conclusion, SPECT/CT-guided ENI is associated with a low risk of contralateral regional failure (2%) and has resulted in significant reduction in the incidence of dysphagia, feeding tube placement, and late xerostomia and improves HRQOL.
Another reason for high rates of radiation-related toxicity is the considerable treatment margin which are empirically determined long time ago. Since then, significant improvements of tumor visualization and demarcation of the border of macroscopic disease extension have been made as a result of integrating co-registered high-quality contrast-enhanced MRI and/or FDG-PET-CT in the delineation process. This has significantly increased the accuracy of identifying the borders of macroscopic disease extension, the GTV. Furthermore, advanced image-guidance during the radiation delivery (daily cone-beam CT) is increasingly used in the daily practice. These recent developments increased the need to re-evaluate the currently used GTV-CTV-PTV margins. Therefore, different radiation centers using these new imaging and image-guided techniques has decided to reduce the radiation margin in order to reduced treatment toxicity. In our institute, the radiation margins were reduced in 2 steps. From April 2015 onwards, the CTV-PTV margin was reduced from 5 to 3 mm and since February 2017, the GTV to high-risk CTV margin was reduced from 10 to 6 mm. We compared the toxicity and outcome of patients treated with the old (largest) margin recipe of GTV-CTV-PTV of 15mm to those treated with the smallest margin recipe of 9mm.
Reducing the total margin by 6mm resulted in significant reduction of the irradiated volumes, the Dmean of different organs at risk with subsequent significant reduction of different acute
and late toxicity end points such as painful mucositis, the need for feeding tube, and late grade ≥2 xerostomia and dysphagia while maintaining loco-regional control. These results are in line with those reported by the Danish group and group of university of California increasing the bulk of evidence that reducing the radiation margins would be associated with reduced toxicity with comparable LRC. These encouraging results might encourage the head and neck radiation oncology community to consider reduction of the radiation margins in order to reduce radiation toxicity, especially in radiation departments where the daily CBCT is used for the image-guidance and integrating co-registered MRI and/or FDG-PET in the delineation process is a routine daily practice.