Interobserver variability in organ at risk delineation in head and neck cancer.

BACKGROUND: In radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines. METHODS: HNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison. RESULTS: Fourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8-0.9); median MSD 1.1 mm, range (0.8-8.3), median HD95 3.4 mm, range (1.5-38.7)], brainstem [median DSC 0.9 (0.6-0.9); median MSD 1.5 mm (1.1-4.0), median HD95 4.0 mm (2.3-15.0)], submandibular glands [median DSC 0.8 (0.5-0.9); median MSD 1.2 mm (0.9-2.5), median HD95 3.1 mm (1.8-12.2)] and parotids [median DSC 0.9 (0.6-0.9); median MSD 1.9 mm (1.2-4.2), median HD95 5.1 mm (3.1-19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008). CONCLUSIONS: Although ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.

Randomized Clinical Trial on Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma: Results on the Quality of Life.

PURPOSE: A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites would result in less toxicity and improvement in Quality of Life (QoL) without compromising tumor control. This paper aimed to compare QoL in both treatment arms. METHODS: Two-hundred head and neck cancer patients treated with radiotherapy (RT) or chemo-RT were randomized (all stages, mean age: 60 years, M/F: 82%/18%). The elective nodal volumes of patients randomized in the experimental arm were treated up to a 40 Gy equivalent dose. In the standard arm, the elective nodal volumes were treated up to a 50 Gy equivalent dose. The QoL data were collected using The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and the EORTC Head and Neck Cancer module (H&N35). RESULTS: A trend toward less decline in QoL during treatment was observed in the 40 Gy arm compared to the 50 Gy arm. Statistically significant differences for global health status, physical functioning, emotional functioning, speech problems, and trouble with social eating in favor of the 40 Gy arm were observed. A clinically relevant better outcome in the 40 Gy arm was found for physical functioning at the end of therapy. CONCLUSION: QoL during RT for head and neck cancer tends to be less impaired in the 40 Gy arm. However, reducing the dose only on the elective neck does not result in clinically relevant improvement of QoL. Therefore, additional treatment strategies must be examined to further improve the QoL of HNSCC patients.

Deep learning for elective neck delineation: More consistent and time efficient.

BACKGROUND/PURPOSE: Delineation of the lymph node levels of the neck for irradiation of the elective clinical target volume in head and neck cancer (HNC) patients is time consuming and prone to interobserver variability (IOV), although international consensus guidelines exist. The aim of this study was to develop and validate a 3D convolutional neural network (CNN) for semi-automated delineation of all nodal neck levels, focussing on delineation accuracy, efficiency and consistency compared to manual delineation. MATERIAL/METHODS: The CNN was trained on a clinical dataset of 69 HNC patients. For validation, 17 lymph node levels were manually delineated in 16 new patients by two observers, independently, using international consensus guidelines. Automated delineations were generated by applying the CNN and were subsequently corrected by both observers separately as needed for clinical acceptance. Both delineations were performed two weeks apart and blinded to each other. IOV was quantified using Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). To assess automated delineation accuracy, agreement between automated and corrected delineations were evaluated using the same measures. To assess efficiency, the time taken for manual and corrected delineations were compared. In a second step, only the clinically relevant neck levels were selected and delineated, once again manually and by applying and correcting the network. RESULTS: When all lymph node levels were delineated, time taken for correcting automated delineations compared to manual delineations was significantly shorter for both observers (mean: 35 vs 52 min, p < 10-5). Based on DSC, automated delineation agreed best with corrected delineation for lymph node levels Ib, II-IVa, VIa, VIb, VIIa, VIIb (DSC >85%). Manual corrections necessary for clinical acceptance were 1.4 mm MSD on average and were especially low (<1mm) for levels II-IVa, VIa, VIIa and VIIb. IOV was significantly smaller with automated compared to manual delineations (MSD: 1.4 mm vs 2.5 mm, p < 10-11). When delineating only the clinically relevant neck levels, the correction time was also significantly shorter (mean: 8 vs 15 min, p < 10-5). Based on DSC, automated delineation agreed very well with corrected delineation (DSC > 87%). Manual corrections necessary for clinical acceptance were 1.3 mm MSD on average. IOV was significantly smaller with automated compared to manual delineations (MSD: 0.8 mm vs 2.3 mm, p < 10-3). CONCLUSION: The CNN developed for automated delineation of the elective lymph node levels in the neck in HNC was shown to be more efficient and consistent compared to manual delineation, which justifies its implementation in clinical practice.

Does intensity-modulated radiation therapy lower the risk of osteoradionecrosis of the jaw? A long-term comparative analysis.

The aim of this study was to analyze the impact of different radiation techniques on the long-term incidence of osteoradionecrosis in head and neck cancer. Risk factors and the occurrence of osteoradionecrosis were analyzed in a retrospective, comparative, observational study. Medical files and radiological images of 109 patients treated with primary intensity-modulated radiation therapy (IMRT) and 129 patients treated with primary three-dimensional conformal radiotherapy (3D-CRT) were evaluated. Proportional hazards models were used to analyse the effects of the radiation modality and patient characteristics on the necrosis risk. Twenty-two patients developed osteoradionecrosis (9.2%) during a mean follow-up of 4.3 years. A numerical difference was observed, with more osteoradionecrosis after 3D-CRT (n=18) than after IMRT (n=4). After correction for group differences and confounders, no statistical difference in risk was observed between the two treatment groups (P=0.37). Multivariate analysis showed evidence of a higher osteoradionecrosis risk for patients with a tumour of the oropharynx and for patients with tooth extraction after radiation therapy. Although the incidence of osteoradionecrosis tended to be lower after IMRT, due to the multifactorial aetiology it remains a severe problem and cannot be prevented by new radiotherapy techniques. Continuous efforts are necessary to control additional risk factors and avoid osteoradionecrosis.

Benefits of deep learning for delineation of organs at risk in head and neck cancer.

PURPOSE/OBJECTIVE: Precise delineation of organs at risk (OARs) in head and neck cancer (HNC) is necessary for accurate radiotherapy. Although guidelines exist, significant interobserver variability (IOV) remains. The aim was to validate a 3D convolutional neural network (CNN) for semi-automated delineation of OARs with respect to delineation accuracy, efficiency and consistency compared to manual delineation. MATERIAL/METHODS: 16 OARs were manually delineated in 15 new HNC patients by two trained radiation oncologists (RO) independently, using international consensus guidelines. OARs were also automatically delineated by applying the CNN and corrected as needed by both ROs separately. Both delineations were performed two weeks apart and blinded to each other. IOV between both ROs was quantified using Dice similarity coefficient (DSC) and average symmetric surface distance (ASSD). To objectify network accuracy, differences between automated and corrected delineations were calculated using the same similarity measures. RESULTS: Average correction time of the automated delineation was 33% shorter than manual delineation (23 vs 34 minutes) (p < 10-6). IOV improved significantly with network initialisation for nearly all OARs (p < 0.05), resulting in decreased ASSD averaged over all OARs from 1.9 to 1.2 mm. The network achieved an accuracy of 90% and 84% DSC averaged over all OARs for RO1 and RO2 respectively, with an ASSD of 0.7 and 1.5 mm, which was in 93% and 73% of the cases lower than the IOV. CONCLUSION: The CNN developed for automated OAR delineation in HNC was shown to be more efficient and consistent compared to manual delineation, which justify its implementation in clinical practice.

Correlation of Patient- and Physician-Scored Dysphagia with Videofluoroscopies in Patients Treated with Radiotherapy for Head and Neck Cancer.

The aim of this study was to investigate the correlation between patient-scored dysphagia and physician-scored dysphagia in head and neck cancer patients treated with radiotherapy. Furthermore, we wanted to compare both patient- and physician-scored dysphagia with dysphagia evaluated on swallowing videofluoroscopies. Sixty-three patients from two different centers treated with radiotherapy for head and neck cancer were evaluated in the current study. Swallowing videofluoroscopies at baseline, 6, and 12 months following radiotherapy were evaluated by 2 observers using the Penetration Aspiration Scale (PAS) and Swallowing Performance Status Scale (SPS) and correlated with patient and physician scored dysphagia. We observed a significant association between physician and patient scored dysphagia (p < 0.01), pre-treatment and post-treatment. Furthermore, the risk of observing dysphagia on videofluoroscopies increased significantly with increasing scores of both physician as well as patient scored dysphagia, and this at all assessed time-points. Patient-scored dysphagia correlates better with dysphagia evaluated by the PAS. Physician-scored dysphagia, however, correlates better with dysphagia as evaluated using the SPS. Both physician- and patient-scored dysphagia correlate well with dysphagia evaluated on videofluoroscopies. Since patient-scored dysphagia correlates better with PAS and changes in the PAS score, and physician-scored dysphagia correlates better with SPS, we advocate to use both patient- and physician-scored dysphagia in future trials.

Salvage Transoral Laser Microsurgery for Radiorecurrent Laryngeal Cancer: Indications, Limits, and Outcomes.

PURPOSE OF REVIEW: The aim of this report is to identify relevant literature reports on salvage transoral laser microsurgery (TLM); to consider its oncologic and functional outcomes, as well as reported complications; and to address indications and limitations of salvage TLM. FINDINGS: The weighted average of local control after first salvage TLM was 57%. Repeated TLM procedures for second or third recurrences were required in up to 41% of cases, resulting in a weighted average of local control with TLM alone of 67%. The rate of definite laryngeal preservation was 73%. The ultimate local control rate, including cases that required total laryngectomy, was 90%. The overall complication rate after salvage TLM was 14%. SUMMARY: Salvage TLM of radiorecurrent laryngeal cancer yields excellent oncologic outcomes. Serious complications are scarce, hospitalization times are short, and functional outcomes in terms of voice and swallowing are favorable when compared to open conservation laryngeal surgery. The key to success is an optimal patient selection.

Basal oxidative stress ratio of head and neck squamous cell carcinomas correlates with nodal metastatic spread in patients under therapy.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that is strongly associated with oxidative damage and oxidative stress. Tobacco and alcohol - sources of massive quantities of reactive oxygen species (ROS) - have been clearly identified as etiologic factors that contribute to these malignancies. Considering the role of glutathione (GSH) in ROS detoxification, we hypothesized that potential biological markers can be found in addition to the parameters of oxidative stress. In line with previous studies that emphasized the accumulation of GSH in tumor cells, in this study, we have reported a lower ratio of oxidized versus reduced GSH in head and neck tumors. OBJECTIVE: The aim of the paper was to evaluate the prognostic and clinical significance of the ratio of oxidized versus reduced GSH in patients with head and neck cancers. METHODS: Thirty-six patients with HNSCC were included in this study. The tumoral redox status was determined by measuring the ratio of oxidized/reduced GSH (GSSG/GSH) by capillary electrophoresis. Statistical analysis was performed to assess the correlation between patient, clinical factors and the redox status. RESULTS: The results showed a low tumoral ratio of GSSG/GSH and a better locoregional control. Moreover, a significant correlation between the tumoral redox status ratio (GSSG/GSH) and nodal stage (N0 versus N1, N2 and N3) was also observed. A higher tumoral redox status ratio was found to be associated with the presence of lymph node metastasis (N1, N2 and N3). CONCLUSION: A strong correlation was observed between the oxidative status and locoregional control of the tumors. Moreover, a higher basal tumoral redox status ratio was found to be correlated with the presence of lymph node metastasis.

The incidence of hypothyroidism after radiotherapy for head and neck cancer.

The incidence of hypothyroidism after radiotherapy for head and neck cancer. OBJECTIVES: To identify the incidence of radiation-induced hypothyroidism (HT) after head and neck radiotherapy.Furthermore, we wanted to correlate patient and treatment characteristics with the incidence of HT in order to identify predictive factors for radiation-induced HT. METHODOLOGY: We examined the values of thyrotropin, i.e., the thyroid-stimulating hormone (TSH), in head and neck cancer patients who received a combination treatment of radiotherapy and chemotherapy between 2005 and 2012. HT was defined as having a TSH value of > 10 mIU/L or whenever the patient started to take substitution therapy after treatment. We correlated the radiotherapy mean dose to the thyroid gland (Dmean), the pretreatment volume of the thyroid gland, sex, age, type of concomitant treatment, tumour localization, and T and N classification with the incidence of HT. RESULTS: We were able to obtain data from 72 patients. From these 72 patients, 48 (66%) had a normal thyroid function and 25 (34%) had developed HT. The mean follow-up for these patients was 55 months (range: 21 to 103 months). Out of the 25 patients with HT, 8 (32%) were diagnosed within the first year of follow-up. Increasing Dmean is a significant risk factor for developing HT. Increasing thyroid volume, on the other hand, was correlated with less HT in our patient cohort. CONCLUSIONS: In our study, the incidence of HT is 34%. We also noticed that HT can even develop shortly after treatment. Patients with a higher Dmean to the thyroid gland and lower pretreatment thyroid gland volumes are more at risk.