O. Hamming-Vrieze

The association of treatment delay and prognosis in head and neck squamous cell carcinoma (HNSCC) patients in a Dutch comprehensive cancer center

OBJECTIVE The increasing volume of head and neck squamous cell carcinoma (HNSCC) patients can lead to longer intervals between histopathological diagnosis and primary treatment. This could cause psychological distress to the patient, but more importantly could possibly lead to tumor progression and decreased survival. Accordingly, this study investigates these relationships. METHODS The correlation of professional delay and clinical characteristics of 2493 patients, treated between 1990 and 2011 with oral, oropharyngeal, hypopharyngeal and laryngeal SCC, was investigated. Patients were divided in two groups based on treatment delay, defined as the interval between histopathological diagnosis and initial treatment. Univariate and multivariate proportional hazards models were used to assess disease specific survival (DSS) and disease free survival (DFS). RESULTS Year of diagnosis, tumor site and therapy were significantly related to treatment delay. Tumor stage was not related to treatment delay. Multivariate regression models revealed that the group with a delay of more than 30 days had a better DSS (HR .838, CI .697-.922, p=.041) and DFS (HR .816, CI .702-.947), p=.007) than the group treated within 30 days. CONCLUSION In our study, treatment delay up to 90 days is not related to impaired survival. This argument can be used extremely cautiously to comfort patients who have to wait several weeks for treatment. Although, possible tumor progression during treatment delay could have led to increased morbidity subsequent to more extensive treatment. Also, possible negative psychological impact of delay in treatment should not be underestimated.

Deformable Image Registration for Adaptive Radiation Therapy of Head and Neck Cancer: Accuracy and Precision in the Presence of Tumor Changes

PURPOSE To compare deformable image registration (DIR) accuracy and precision for normal and tumor tissues in head and neck cancer patients during the course of radiation therapy (RT). METHODS AND MATERIALS Thirteen patients with oropharyngeal tumors, who underwent submucosal implantation of small gold markers (average 6, range 4-10) around the tumor and were treated with RT were retrospectively selected. Two observers identified 15 anatomical features (landmarks) representative of normal tissues in the planning computed tomography (pCT) scan and in weekly cone beam CTs (CBCTs). Gold markers were digitally removed after semiautomatic identification in pCTs and CBCTs. Subsequently, landmarks and gold markers on pCT were propagated to CBCTs, using a b-spline-based DIR and, for comparison, rigid registration (RR). To account for observer variability, the pair-wise difference analysis of variance method was applied. DIR accuracy (systematic error) and precision (random error) for landmarks and gold markers were quantified. Time trend of the precisions for RR and DIR over the weekly CBCTs were evaluated. RESULTS DIR accuracies were submillimeter and similar for normal and tumor tissue. DIR precision (1 SD) on the other hand was significantly different (P<.01), with 2.2 mm vector length in normal tissue versus 3.3 mm in tumor tissue. No significant time trend in DIR precision was found for normal tissue, whereas in tumor, DIR precision was significantly (P<.009) degraded during the course of treatment by 0.21 mm/week. CONCLUSIONS DIR for tumor registration proved to be less precise than that for normal tissues due to limited contrast and complex non-elastic tumor response. Caution should therefore be exercised when applying DIR for tumor changes in adaptive procedures.

mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers : Development of a new method

Interstitial photodynamic therapy (iPDT) can be an option in the management of locally recurrent base of tongue cancer after (chemo)radiation treatment. The purpose of the current study was to develop a technique to implant light sources into the tumor tissue.

Evaluation of long term (10-years+) dysphagia and trismus in patients treated with concurrent chemo-radiotherapy for advanced head and neck cancer.

OBJECTIVES Assessment of long term (10-years+) swallowing function, mouth opening, and quality of life (QoL) in head and neck cancer (HNC) patients treated with chemo-radiotherapy (CRT) for advanced stage IV disease. MATERIALS AND METHODS Twenty-two disease-free survivors, participating in a multicenter randomized clinical trial for inoperable HNC (1999-2004), were evaluated to assess long-term morbidity. The prospective assessment protocol consisted of videofluoroscopy (VFS) for obtaining Penetration Aspiration Scale (PAS) and presence of residue scores, Functional Oral Intake Scale (FOIS) scores, maximum mouth opening measurements, and (SWAL-QOL and study-specific) questionnaires. RESULTS At a median follow-up of 11-years, 22 patients were evaluable for analysis. Ten patients (46%) were able to consume a normal oral diet without restrictions (FOIS score 7), whereas 12 patients (54%) had moderate to serious swallowing issues, of whom 3 (14%) were feeding tube dependent. VFS evaluation showed 15/22 patients (68%) with penetration and/or aspiration (PAS⩾3). Fifty-five percent of patients (12/22) had developed trismus (mouth opening⩽35mm), which was significantly associated with aspiration (p=.011). Subjective swallowing function (SWAL-QOL score) was impaired across almost all QoL domains in the majority of patients. Patients treated with IMRT showed significantly less aspiration (p=.011), less trismus (p=.035), and less subjective swallowing problems than those treated with conventional radiotherapy. CONCLUSION Functional swallowing and mouth opening problems are substantial in this patient cohort more than 10-years after organ-preservation CRT. Patients treated with IMRT had less impairment than those treated with conventional radiotherapy.

FDG-PET and diffusion-weighted MRI in head-and-neck cancer patients: Implications for dose painting

PURPOSE The purpose of this study was to investigate if FDG-PET and DWI identify the same or different targets for dose escalation in the GTV of HN cancer patients. Additionally, the dose coverage of DWI-targets in an FDG-PET-based dose painting plan was analyzed. MATERIALS AND METHODS Eighteen HN cancer patients underwent FDG-PET and DWI exams, which were converted to standardized uptake value (SUV)- and apparent diffusion coefficient (ADC)-maps. The correspondence between the two imaging modalities was determined on a voxel-level using Spearmans correlation coefficient (ρ). Dose painting plans were optimized based on the 50% isocontour of the maximum SUV ( SUV(50%max)). Dose coverage was analyzed in three different SUV- and three different ADC-targets using the mean dose and the near-minimum and near-maximum doses. RESULTS The average maximum SUV was 13.9 and the mean ADC was 1.17 · 10(-3) mm(2)/s. The average ρ between SUV and ADC was -0.2 (range: -0.6 to 0.4). The ADC-targets were only partly overlapping the SUV(50%max)-target and the dose parameters were significantly smaller in the ADC-targets compared to the SUV(50%max)-target. CONCLUSIONS FDG-PET and DWI contain different information, resulting in different targets. Further information about failure patterns and dose relations can be obtained by adding DWI to currently ongoing dose painting trials.

Primary Treatment Results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia

Introduction Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. Methods All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. Results In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18–35) from day of diagnosis. Conclusion The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.

T3‐T4 laryngeal cancer in The Netherlands Cancer Institute; 10‐year results of the consistent application of an organ‐preserving/‐sacrificing protocol

Both organ‐preserving concurrent (chemo)radiotherapy ((C)RT) and organ‐sacrificing surgery (total laryngectomy) are used for treatment of advanced laryngeal cancer. The purpose of this study was to present the assessment of our treatment protocol for T3 (C)RT and T4 disease (total laryngectomy + postoperative RT).

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.

Total Laryngectomy for a Dysfunctional Larynx After (Chemo)Radiotherapy

OBJECTIVE To evaluate the functional outcomes after total laryngectomy (TLE) for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (chemo)radiotherapy. DESIGN Retrospective cohort study. SETTING Tertiary comprehensive cancer center. PATIENTS The study included 25 patients from a cohort of 217 consecutive patients with TLE who were treated between January 2000 and July 2010. The inclusion criteria for this subgroup analysis were complete remission and functional problems for which TLE was considered to be the only resolution. Quality of life assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 questionnaires and an additional study-specific questionnaire covering functional aspects, such as swallowing and dyspnea, in more detail. INTERVENTION Total laryngectomy. MAIN OUTCOME MEASURES Morbidity, mortality, and functional outcomes. RESULTS The indication for TLE was chronic aspiration with or without recurrent pneumonia (n = 15 [60%]), debilitating dyspnea (n = 8 [32%]), and persistent profuse hemorrhage (radiation ulcer) (n = 2 [8%]). After TLE, 14 of the 25 patients (56%) had 20 major postoperative complications, including 11 pharyngocutaneous fistulas, requiring additional treatment. Tube feeding and recurrent pneumonia incidence had decreased from 80% and 28% to 29% and 0%, respectively, 2 years after surgery. Prosthetic voice rehabilitation was possible in 19 patients (76%). Two years after surgery, 10 of 14 patients (71%) still reported TLE-related pulmonary problems despite the consistent use of a heat and moisture exchanger. The 5-year overall survival rate was 35%. CONCLUSIONS Total laryngectomy for a dysfunctional larynx tends to have a high complication rate. However, in this study, the initial functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Tube feeding was significantly reduced, and the quality of life of the surviving patients appeared to be reasonable.

Regional Control of Melanoma Neck Node Metastasis After Selective Neck Dissection With or Without Adjuvant Radiotherapy

OBJECTIVE To examine the effect of adjuvant radiotherapy on regional control of melanoma neck node metastasis. DESIGN A single-institution retrospective study. SETTING Tertiary care cancer center. PATIENTS The study included 64 patients with melanoma neck node metastasis who were treated with neck dissection between 1989 and 2004 in The Netherlands Cancer Institute, Amsterdam. Twenty-four patients were treated with surgery only (15 modified radical neck dissections [MRNDs] and 9 selective neck dissections [SNDs]) (S group), and 40 patients underwent surgery (28 MRNDs and 12 SNDs) and adjuvant radiotherapy (S+RT group). RESULTS Prognostic factors, ie, number of nodes, size of nodes, and extracapsular extension, were worse in the S+RT group. With a median follow-up of 2.5 years, the 2-year ipsilateral regional recurrence (RR) rate was 18% in the S+RT group and 46% in the S group. This 28% difference in RR was not statistically significant (P = .16). However, evaluation of the effect of adjuvant RT in multivariate analysis revealed a significant reduction of the RR rate after correction for the number of involved nodes (P = .04). In the S group, SND was associated with a trend toward worse RR rate compared with MRND but was not statistically significant in univariate analysis (P = .08). The type of neck dissection did not influence the RR rate in the S+RT group (P = .60). Three of the 4 RRs occurred outside the dissected volume after SND in the S group. CONCLUSIONS Based on our findings, we conclude that, compared with extended neck dissection, SND leads to inferior regional control in patients with melanoma neck node metastasis who are not treated with RT, even those with low-risk neck disease. Furthermore, our results suggest that adjuvant RT improves regional control in patients with 2 or more involved nodes.