J. Friborg

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study

BACKGROUNDnHuman papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer.nnnMETHODSnThe ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification.nnnFINDINGSnOf 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages.nnnINTERPRETATIONnOur proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification.nnnFUNDINGnNone.

Primary transoral robotic surgery with concurrent neck dissection for early stage oropharyngeal squamous cell carcinoma implemented at a Danish head and neck cancer center: a phase II trial on feasibility and tumour margin status

There is an increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the western world due to human papillomavirus (HPV). According to the Danish Head and Neck Cancer Group guidelines, the current recommended treatment of patients with OPSCC in Denmark is primary radiation therapy (RT) with or without concomitant chemotherapy. This is the first study in Scandinavia from a head and neck cancer centre that aims to demonstrate the feasibility of performing primary transoral robotic surgery (TORS) and concurrent neck dissection for patients with early stage OPSCC. Between September 2014 and January 2016, 30 consecutive patients with clinical T1–T2, N0–N1 OPSCC underwent primary TORS and concurrent neck dissection. The patients were offered postoperative adjuvant therapy according to pathological risk parameters: pT >2, T-site margin <2xa0mm, pN >1 or extracapsular extension (ECE). Concomitant chemotherapy was offered to patients with the presence of ECE or involved margins. Twenty-nine patients had negative margins on T-site after primary resection. Only one patient had a close margin of 1xa0mm. Unilateral neck dissection was performed in 21 patients while nine patients underwent bilateral neck dissection. Due to an upstaging following surgery, 13 patients were referred to adjuvant therapy. Four of these patients received RT and two patients received concomitant chemo-radiation (CCR) therapy. Seven patients declined the recommended adjuvant therapy one of whom later developed an N-site recurrence and received salvage surgery with postoperative RT. In summary, 43% of the patients were referred to adjuvant therapy following primary surgery which was mainly due to N-site stage migration and ECE. Primary TORS and concurrent neck dissection is a safe and feasible procedure that may be an alternative to primary RT and CCR in a selected group of patients with early stage OPSCC.

Metal artefact reduction for accurate tumour delineation in radiotherapy

Background and purpose Two techniques for metal artefact reduction for computed tomography were studied in order to identify their impact on tumour delineation in radiotherapy. Materials and methods Using specially designed phantoms containing metal implants (dental, spine and hip) as well as patient images, we investigated the impact of two methods for metal artefact reduction on (A) the size and severity of metal artefacts and the accuracy of Hounsfield Unit (HU) representation, (B) the visual impact of metal artefacts on image quality and (C) delineation accuracy. A metal artefact reduction algorithm (MAR) and two types of dual energy virtual monochromatic (DECT VM) reconstructions were used separately and in combination to identify the optimal technique for each implant site. Results The artefact area and severity was reduced (by 48–76% and 58–79%, MAR and DECT VM respectively) and accurate Hounsfield-value representation was increased by 22–82%. For each energy, the observers preferred MAR over non-MAR reconstructions (pu202f<u202f0.01 for dental and hip cases, pu202f<u202f0.05 for the spine case). In addition, DECT VM was preferred for spine implants (pu202f<u202f0.01). In all cases, techniques that improved target delineation significantly (pu202f<u202f0.05) were identified. Conclusions DECT VM and MAR techniques improve delineation accuracy and the optimal of reconstruction technique depends on the type of metal implant.

OC-0153: Dual energy CT and iterative metal artefact reduction for accurate tumour delineation

Material and Methods: A set of teeth containing an amalgamfilled removable tooth and an artificial polycaprolactone tumour was placed in water and CT scanned (Siemens Somatom Definition AS) at 120 kVp, 80 kVp, and 140 kVp. The two latter scans were used to reconstruct virtual monochromatic (VM) images. All image sets were additionally reconstructed with metal artefact reduction (MAR) software (iMAR, Siemens Healthcare). The following 4 MAR reconstructions were studied: 1) 130 keV VM 2) 70 keV VM with MAR, 3) 120 kVp with MAR, 4) 130 keV VM with MAR. A conventional 120 kVp CT was also taken and a 120 kVp image where the metal tooth was removed was used as control. 3 oncologists and 2 radiologists contoured the tumour volume on all 6 image sets while blinded to the image reconstruction type. A 7th high-quality image of only the artificial tumour was contoured to obtain the true shape of the tumour. Maximal Hausdorff distances and DICE coefficients of the 5 delineated contours compared to the true contour was were used to quantify delineation accuracy in all 6 image sets. Statistically, a Friedman-test was used for primary comparisons and a Nemenyi-test is performed for pairwise post hoc analysis.