Arash Navran

3D Variation in delineation of head and neck organs at risk

BackgroundConsistent delineation of patient anatomy becomes increasingly important with the growing use of highly conformal and adaptive radiotherapy techniques. This study investigates the magnitude and 3D localization of interobserver variability of organs at risk (OARs) in the head and neck area with application of delineation guidelines, to establish measures to reduce current redundant variability in delineation practice.MethodsInterobserver variability among five experienced radiation oncologists was studied in a set of 12 head and neck patient CT scans for the spinal cord, parotid and submandibular glands, thyroid cartilage, and glottic larynx. For all OARs, three endpoints were calculated: the Intraclass Correlation Coefficient (ICC), the Concordance Index (CI) and a 3D measure of variation (3D SD).ResultsAll endpoints showed largest interobserver variability for the glottic larynx (ICC = 0.27, mean CI = 0.37 and 3D SD = 3.9 mm). Better agreement in delineations was observed for the other OARs (range, ICC = 0.32-0.83, mean CI = 0.64-0.71 and 3D SD = 0.9-2.6 mm). Cranial, caudal, and medial regions of the OARs showed largest variations. All endpoints provided support for improvement of delineation practice.ConclusionsVariation in delineation is traced to several regional causes. Measures to reduce this variation can be: (1) guideline development, (2) joint delineation review sessions and (3) application of multimodality imaging. Improvement of delineation practice is needed to standardize patient treatments.

The influence of nodal yield in neck dissections on lymph node ratio in head and neck cancer

OBJECTIVES Recent studies suggest that lymph node ratio (LNR) is a strong prognostic factor in head and neck cancer. This study aims to determine if the yield of harvested lymph nodes (LNs) influences the LNR. METHODS The study included 522 head and neck cancer patients, undergoing 638 primary and salvage (selective) neck dissections between 2002 and 2012. Before 2007 the neck dissection specimens were macroscopically and microscopically examined by pathologists and after 2007 the macroscopic examination was performed by pathology technicians. For comparison of mean LN yields, univariate and multivariate analyses were performed. RESULTS The mean number of LNs among 374 specimens examined by pathologists was 24 (range 0-89) vs. 32 (range 2-89) among 264 specimens examined by pathology technicians (P<.001). This caused the mean LNR in the non pre-treated patient group to drop from 11.4% to 8.7%. The counts of LNs per type of neck dissection were significantly different and increased with the number of levels involved. However, there was no linear relationship and the higher yields could be mostly ascribed to LNs in level V. The LNR varied from 8.1% to 18.4% among the different types of neck dissections. CONCLUSIONS A significant increase in the number of harvested LNs, but a decrease in LNR was observed after introducing pathology technicians for macroscopic examination. A clear association between the extent of the dissection and the number of harvested LNs was observed. LNR appears to be strongly dependent on the harvesting protocol and the extent of the dissection.

MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: Description of the method

Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep‐seated recurrent head and neck cancers.

Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review

BACKGROUND The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted. METHODS PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated. RESULTS Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p=0.008), and involvement of midline (p=0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p=0.344). CONCLUSION The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups.

Baseline peripheral blood leukocytosis: Biological marker predicts outcome in oropharyngeal cancer, regardless of HPV-status

OBJECTIVES To study the prognostic value of abnormalities in baseline complete blood count in patients with oropharyngeal cancer (OPC) treated with (chemo) radiation. METHODS AND MATERIALS The prognostic value of baseline complete blood count on outcome in 234 patients with OPC treated between 2010 and 2015 was examined in multivariate analysis together with other conventional prognostic variables including HPV-status, tumor stage, tumor and nodal size. RESULTS The 3-year overall survival (OS), disease-free survival (DFS), locoregional control (LRC), and distant control (DC) of the whole group were 74%, 64%, 79%, and 88%, respectively. Leukocytosis and HPV-status were the only significant prognosticators for OS and DFS at the multivariate analysis. Patients without leukocytosis had a significantly better DC compared to those with leukocytosis (92% and 70%, respectively, p < 0.001). Patients with HPV-negative OPC had significantly worse LRC compared to HPV-positive patients (67% and 90%, respectively, p < 0.001). The 3-year OS in HPV-positive group with leukocytosis compared to those without leukocytosis were 69% and 95%, respectively (p < 0.001). The figures for HPV-negative patients were 41% vs. 61%, respectively (p = 0.010). CONCLUSIONS This is the first study to date reporting the independent impact of leukocytosis and HPV-status on outcome of patients with OPC. The poor outcome of patients with leukocytosis is mainly caused by the worse DC. The significant impact of leukocytosis on outcome was even more pronounced in HPV-positive patients. These biomarkers could help identifying patients with poor prognosis at baseline requiring intensification of local and/or systemic treatment while treatment de-intensification might be offered to the low-risk group.

A predictive model for residual disease after (chemo) radiotherapy in oropharyngeal carcinoma: Combined radiological and clinical evaluation of tumor response

Background and purpose Early detection of Residual disease (RD) is vital for salvage possibilities after (chemo) radiatiotherapy for oropharyngeal carcinoma (OPC). We standardized clinical investigation to test its added value to MRI response evaluation and investigated the benefit of FDG-PET/CT. Materials and methods Radiological response evaluation using Ojiri-score was done for 234 patients with OPC, using MRI 12 weeks after (chemo) radiotherapy between 2010 and 2014. The presence of mucosal lesions and/or major complaints (still completely tube feeding-dependent and/or opiate-dependent because of swallowing problems) was scored as clinical suspicion (CS). Retrospectively, the performance of Ojiri to predict RD was compared to CS and both combined using Pearson Chi-squared. Of the whole group, FDG-PET/CT metabolic response (MR) was available in 50 patients. Results Twelve out of 234 patients (5.1%) had RD. Ojiri and CS had excellent negative predictive value (NPV) (98% and 100% respectively). The combination of CS and Ojiri reduced false positives by 32% (38–26 patients) without lowering NPV (98%). No patients with complete MR (n = 39) at the FDG-PET/CT had RD compared to 5 (45%) with partial MR. Conclusion For response evaluation in OPC, the combination of CS and Ojiri-score improved the predictive accuracy by reducing false positives compared to them individually. FDG-PET/CT is promising to further reduce false positives.

Orthovoltage for basal cell carcinoma of the head and neck: Excellent local control and low toxicity profile

Evaluation of treatment results of orthovoltage X‐rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile.

The impact of margin reduction on outcome and toxicity in head and neck cancer patients treated with image-guided volumetric modulated arc therapy (VMAT)

BACKGROUND AND PURPOSE In recent decades, outcomes of patients with head and neck cancer (HNC) have improved as a result of implementing several strategies, such as chemoradiation. However, these improvements were achieved at the cost of increased toxicity. One way to reduce radiation-related toxicity is by reducing the margins. MATERIALS AND METHODS Between 2013 and 2016, 206 consecutive patients were treated with CTV-PTV margin of 5 mm and subsequently 208 patients with 3 mm margin. This study evaluates the impact of reducing clinical target volume (CTV) to planning target volume (PTV) margin on outcome and toxicity. RESULTS All patients were treated with volumetric modulated arc therapy (VMAT) with daily-image guidance using cone-beam CT (CBCT). Overall acute grade 3 toxicity was significantly lower in 3 mm-group, compared to 5 mm-group (53.8% vs. 65%, respectively, p = 0.032). The same was true for acute grade 3 mucositis (30.8% vs. 42.2%, p = 0.008) and for acute grade 3 dysphagia (feeding tube-dependence) (22.1% vs. 33.5%, p = 0.026). The incidence of ongoing feeding tube-dependence after 3 months of radiotherapy was 11.1% and 20.4%, respectively (p = 0.012). The 2-year incidence of late grade ≥2 xerostomia was 15.8% and 19.4% (p = 0.8). The 2-year loco-regional control rates of patients treated in 3 mm and 5 mm-groups were 79.9% and 79.2% (p = 1.0). The figures for disease-free survival were 71.5% and 72.7 (p = 0.6) and for overall survival were 75.2% and 75.1% (p = 0.9). CONCLUSION Reducing the CTV-PTV margin from 5 to 3 mm combined with daily CBCT-guided VMAT reduced the severity, frequency, and duration of radiation-related toxicity without jeopardizing outcome.

Local control in sinonasal malignant melanoma: Comparing conventional to hypofractionated radiotherapy

The purpose of this study was to analyze the effect of fractionation schedule on local control in postoperative radiotherapy (RT) for sinonasal malignant melanoma.

Orthovoltage X-rays for Postoperative Treatment of Resected Basal Cell Carcinoma in the Head and Neck Area

Background: Surgery is the golden standard for treating basal cell carcinomas. In case of positive tumor margins or recurrent disease, postoperative adjuvant or salvaging therapy is suggested to achieve good local control. Objective: To retrospectively report on local control and toxicity of postoperative radiotherapy by means of orthovoltage X-rays for residual or recurrent basal cell carcinoma after surgery in the head and neck area. Methods: Sixty-six surgically resected residual or recurrent basal cell carcinomas of the head and neck region were irradiated postoperatively by means of orthovoltage X-rays at the Netherlands Cancer Institute between January 2000 and February 2015. Results: After a median follow-up duration of 30.5 months, only 5 recurrences were reported. The 5-year local control rates at 1, 3, and 5 years were 100%, 87%, and 87%, respectively. The 5-year local control rate was 92% for immediate postoperative radiotherapy of incompletely resected basal cell carcinomas, 90% for recurrences after 1 previously performed excision, and 71% for multiple recurrences, namely, a history of more than 1 excision (P = .437). Acute toxicity healed spontaneously within 3 months. Late toxicities were mild. Conclusion: Radiotherapy by means of orthovoltage X-ray is an excellent alternative for re-excision in case of incompletely resected or recurrent basal cell carcinomas that are at risk of serious functional and cosmetic impairments after re-excision, with a 5-year local control rate of 87% and a low toxicity profile.