Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer.

Background: The role of postoperative external beam radiotherapy (EBRT) in patients with residual iodine refractory-differentiated thyroid cancer (IR-DTC) is still inconclusive. The aim of this retrospective study was to evaluate locoregional control (LRC) and overall survival (OS), and potential side effects after postoperative EBRT for both microscopic and macroscopic non-radically resected, locally advanced IR-DTC. Methods: Between 1990 and 2016, 49 patients with locally advanced IR-DTC received EBRT for microscopic (R1; n = 28) or macroscopic (R2; n = 21) locoregional residual disease. For more insight into the added effect of EBRT, we performed an intrapatient sub-analysis in 32 patients who had undergone more than 1 surgical intervention, comparing LRC after primary, curative-intended surgery with LRC after repeated surgery plus EBRT. To estimate LRC and OS, we used Kaplan-Meier curves. From 2007 onward, we prospectively recorded toxicity data in our head and neck cancer database (n = 10). Results: LRC rates 5 years after EBRT were higher for R1 (84.3%) than for R2 (44.9%) residual disease (P = 0.016). The 5-year OS rate after EBRT was 72.1% for R1 and 33.1% for R2 disease (P = 0.003). In the intrapatient analysis (n = 32), LRC rates were 6.3% 5 years after only initial surgery and 77.9% after repeated surgery with EBRT (P < 0.001). Acute toxicity was limited to grade I and II xerostomia, mucositis, and hoarseness; only one patient developed late grade III dysphagia. Conclusions: Postoperative EBRT is associated with long-lasting LRC and OS with acceptable toxicity in patients with locally advanced IR-DTC, especially in microscopic residual disease.

Parotid Gland Stem Cell Sparing Radiation Therapy for Patients With Head and Neck Cancer: A Double-Blind Randomized Controlled Trial.

PURPOSE: Radiation therapy for head and neck cancer frequently leads to salivary gland damage and subsequent xerostomia. The radiation response of the parotid glands of rats, mice, and patients critically depends on dose to parotid gland stem cells, mainly located in the gland's main ducts (stem cell rich [SCR] region). Therefore, this double-blind randomized controlled trial aimed to test the hypothesis that parotid gland stem cell sparing radiation therapy preserves parotid gland function better than currently used whole parotid gland sparing radiation therapy. METHODS AND MATERIALS: Patients with head and neck cancer (n = 102) treated with definitive radiation therapy were randomized between standard parotid-sparing and stem cell sparing (SCS) techniques. The primary endpoint was >75% reduction in parotid gland saliva production compared with pretreatment production (FLOW12M). Secondary endpoints were several aspects of xerostomia 12 months after treatment. RESULTS: Fifty-four patients were assigned to the standard arm and 48 to the SCS arm. Only dose to the SCR regions (contralateral 16 and 11 Gy [P = .004] and ipsilateral 26 and 16 Gy [P = .001] in the standard and SCS arm, respectively) and pretreatment patient-rated daytime xerostomia (35% and 13% [P = .01] in the standard and SCS arm, respectively) differed significantly between the arms. In the SCS arm, 1 patient (2.8%) experienced FLOW12M compared with 2 (4.9%) in the standard arm (P = 1.00). However, a trend toward better relative parotid gland salivary function in favor of SCS radiation therapy was shown. Moreover, multivariable analysis showed that mean contralateral SCR region dose was the strongest dosimetric predictor for moderate-to-severe patient-rated daytime xerostomia and grade ≥2 physician-rated xerostomia, the latter including reported alteration in diet. CONCLUSIONS: No significantly better parotid function was observed in SCS radiation therapy. However, additional multivariable analysis showed that dose to the SCR region was more predictive of the development of parotid gland function-related xerostomia endpoints than dose to the entire parotid gland.

Relationship between videofluoroscopic and subjective (physician- and patient- rated) assessment of late swallowing dysfunction after (chemo) radiation: Results of a prospective observational study.

BACKGROUND AND PURPOSE: Primary (chemo)radiation (CHRT) for HNC may lead to late dysphagia. The purpose of this study was to assess the pattern of swallowing disorders based on prospectively collected objective videofluoroscopic (VF) assessment and to assess the correlations between VF findings and subjective (physician- and patient-rated) swallowing measures. MATERIAL AND METHODS: 189 consecutive HNC patients receiving (CH)RT were included. Swallowing evaluation at baseline and 6 months after treatment (T6) encompassed: CTCAE v.4.0 scores (aspiration/dysphagia), PROMs: SWAL QOL/ EORTC QLQ-H&N35 (swallowing domain) questionnaires and VF evaluation: Penetration Aspiration Scale, semi-quantitative swallowing pathophysiology evaluation, temporal measures and oral/pharyngeal residue quantification. Aspiration specific PROMs (aPROMs) were selected. Correlations between late penetration/aspiration (PA_T6) and: clinical factors, CTCAE and aPROMs were assessed using uni- and multivariable analysis. RESULTS: Prevalence of PA increased from 20% at baseline to 43% after treatment (p < 0.001). The most relevant baseline predictors for PA_T6 were: PA_T0, age, disease stage III-IV, bilateral RT and baseline aPROM 'Choking when drinking' (AUC: 0.84). In general aPROMs correlated better with VF-based PA than CTCAE scores. The most of physiological swallowing components significantly correlated and predictive for PA (i.e. Laryngeal Vestibular Closure, Laryngeal Elevation and Pharyngeal Contraction) were prone to radiation damage. CONCLUSION: The risk of RT-induced PA is substantial. Presented prediction models for late penetration/aspiration may support patient selection for baseline and follow-up VF examination. Furthermore, all aspiration related OARs involved in aforementioned swallowing components should be addressed in swallowing sparing strategies. The dose to these structures as well as baseline PROMs should be included in future NTCP models for aspiration.

Risk of ischaemic cerebrovascular events in head and neck cancer patients is associated with carotid artery radiation dose.

BACKGROUND AND PURPOSE: Radiotherapy in the head and neck area may cause vascular damage to the carotid arteries, increasing the risk of anterior circulation ischaemic cerebrovascular events (ICVEs). However, limited data exists on the relationship between radiation dose to the carotid arteries and risk of ICVE. The purpose of this study was therefore to determine the relationship between radiation dose to the carotid arteries and anterior circulation ICVE risk. MATERIALS AND METHODS: A retrospective analysis of a prospective study cohort of 750 head and neck cancer patients treated with definitive (chemo)radiotherapy was performed. Carotid arteries were delineated, and dose-volume parameters of the treatment plans were calculated. ICVEs were scored prospectively and checked retrospectively by analysing all patient records. Cox proportional hazards analysis was performed to analyse the dose-effect relationships. RESULTS: The median follow-up period was 3.4 years, 27 patients experienced an ICVE and the 5-year cumulative risk was 4.6%. ICVE risk was significantly associated with dose to the carotid arteries. Multivariable analysis showed that the absolute volume (cm3) of the carotid arteries that received at least a radiation dose of 10 Gy was the most important prognostic factor for ICVE (HR = 1.11, AUC = 0.68, p < 0.001). CONCLUSION: This is the first large prospective cohort study that demonstrates an independent dose-effect relationship between radiation dose to the carotid arteries and the risk of ICVE. These findings may be used to identify patients at risk for ICVE after radiotherapy who may benefit from primary or secondary preventive measures.

Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy.

BACKGROUND AND PURPOSE: Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). MATERIALS AND METHODS: HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan-Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. RESULTS: The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). CONCLUSION: Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity.

Outcomes of surgery and postoperative radiation therapy in managing medullary thyroid carcinoma.

BACKGROUND AND OBJECTIVES: We evaluated the outcomes of surgery with or without postoperative radiation therapy (PORT) in the management of medullary thyroid carcinoma (MTC). METHODS: From two tertiary cancer centers, 297 consecutive patients with MTC treated with PORT (n = 46) between 1990 and 2016 or surgery alone (n = 251) between 2000 and 2016 were reviewed. RESULTS: Ten-year cumulative incidences of locoregional and distant failure were 30.2% and 24.9% in the surgery cohort, and 16.9% and 55.2% in the PORT cohort. In the surgery alone cohort, T4 disease, extrathyroidal extension, N1 disease, extranodal extension (ENE), and residual disease after surgery were associated with local failure. The PORT cohort had significantly higher proportions of patients with T4 disease, N1 disease, ENE, and residual disease. CONCLUSIONS: High-risk clinical features can help identify patients with MTC at high-risk for local failure after surgery alone. Patients with high-risk clinical features had effective locoregional control after PORT.

Functional Swallowing Units (FSUs) as organs-at-risk for radiotherapy. PART 2: Advanced delineation guidelines for FSUs.

BACKGROUND AND PURPOSE: In a separate article (PART 1), a rationale and explanation of the physiology-and-anatomy-based concept of Functional Swallowing Units (FSUs) was presented. FSUs are swallowing muscles not included in the set of commonly defined swallowing organs at risk (SWOARs). They are involved in three crucial swallowing components: hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion. This paper is a continuation of PART 1 and it provides detailed computed tomography (CT)-based delineation guidelines for FSUs, which presumably are also at risk of radiation-induced dysphagia. MATERIAL AND METHODS: Following analysis of swallowing physiology and human anatomy, presented in PART 1, CT-based delineation guidelines for defined FSUs were created. Delineation was performed by the first author and revised by a panel of experts. RESULTS AND CONCLUSIONS: Detailed delineation guidelines are presented for seven FSUs involved in HLE, TBR and tongue motion. The guidelines are supplemented by CT and MRI-based exemplary illustrations and complete CT/MRI-based delineation atlases (available online). This paper provides information essential to the implementation of the FSU concept in radiation practice, and supports uniform contouring, data collection and further improvement of swallowing sparing radiation-based strategies.

Functional Swallowing Units (FSUs) as organs-at-risk for radiotherapy. PART 1: Physiology and anatomy.

BACKGROUND AND PURPOSE: When optimising radiotherapy treatments today, the pharyngeal constrictor muscles and the larynx are usually regarded as the swallowing organs at risk (SWOARs). The purpose of this study was to identify and describe additional, previously undefined groups of muscles (functional units) involved in crucial components of swallowing (hyolaryngeal elevation (HLE), tongue base retraction (TBR) and tongue motion), and to emphasise their relevance in radiation-induced dysphagia. MATERIAL AND METHODS: Based on available literature on human anatomy and swallowing physiology, the functional units of muscles involved in HLE, TBR and tongue motion have been identified and described. RESULTS AND CONCLUSION: Functional swallowing units (FSUs) were defined as groups of swallowing muscles sharing their function, that are in close proximity to each other. Seven FSUs involved in HLE, TBR and tongue motion were identified: floor of mouth, thyrohyoid muscles, posterior digastric/stylohyoid muscles complex, longitudinal pharyngeal muscles, hyoglossus/styloglossus muscles complex, genioglossus muscles, intrinsic tongue muscles. The swallowing physiology and anatomy of the FSUs described in this paper will lead to a greater understanding of radiation-induced dysphagia mechanisms and, consequently, to an improvement in the development of swallowing sparing strategies. This article (PART 1) serves as the theoretical foundation for a subsequent article (PART 2), which provides detailed delineation guidelines for FSUs.

Multidisciplinary first-day consultation accelerates diagnostic procedures and throughput times of patients in a head-and-neck cancer care pathway, a mixed method study.

BACKGROUND: Head and neck cancers are fast growing tumours that are complex to diagnose and treat. Multidisciplinary input into organization and logistics is critical to start treatment without delay. A multidisciplinary first-day consultation (MFDC) was introduced to reduce throughput times for patients suffering from head and neck cancer in the care pathway. In this mixed method study we evaluated the effects of introducing the MFDC on throughput times, number of patient hospital visits and compliance to the Dutch standard to start treatment within 30 calendar-days. METHODS: Data regarding 'days needed for referral', 'days needed for diagnostic procedures', 'days to start first treatment', and 'number of hospital visits' (process indicators) were retrieved from the medical records and analysed before and after implementation of the MFDC (before implementation: 2007 (n = 21), and after 2008 (n = 20), 2010 (n = 24) and 2013 (n = 24)). We used semi-structured interviews with medical specialists to explore a sample of outliers. RESULTS: Comparing 2007 and 2008 data (before and after MFDC implementation), days needed for diagnostic procedures and to start first treatment reduced with 8 days, the number of hospital visits reduced with 1.5 visit on average. The percentage of new patients treated within the Dutch standard of 30 calendar-days after intake increased from 52 to 83%. The reduction in days needed for diagnostic procedures was sustainable. Days needed to start treatment increased in 2013. Semi-structured interviews revealed that this delay could be attributed to new treatment modalities, patients needed more time to carefully consider their treatment options or professionals needed extra preparation time for organisation of more complex treatment due to early communication on diagnostic procedures to be performed. CONCLUSIONS: A MFDC is efficient and benefits patients. We showed that the MFDC implementation in the care pathway had a positive effect on efficiency in the care pathway. As a consequence, the extra efforts of four specialist disciplines, a nurse practitioner, and a coordinating nurse seeing the patient together during intake, were justified. Start treatment times increased as a result of new treatment modalities that needed more time for preparation.

Viable tumor in salvage neck dissections in head and neck cancer: Relation with initial treatment, change of lymph node size and human papillomavirus.

OBJECTIVES: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. MATERIALS AND METHODS: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in combination with carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12). RESULTS: Viable tumor was detected in 41% of all neck dissections. Univariate analysis revealed initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI: 2.28-21.07, p < .001), increased lymph node size after initial treatment compared to pretreatment CT scan (OR 20.48, 95%CI: 2.46-170.73, p = .005), more extensive neck dissections (OR 8.40, 95%CI: 2.94-23.98, p < .001), and human papillomavirus negative cancer (OR 4.22, 95%CI: 1.10-16.22, p = .036) as predictors of viable tumor. Patients with decreased or stable, but persistently enlarged lymph node size after chemoradiation had a significantly lower chance of viable tumor (OR 0.15, 95%CI: 0.05-0.41, p < .001). Disease-specific 5-year survival was 34% in case of viable tumor, and 78% when no viable tumor was found (p < .001). CONCLUSIONS: Viable tumor in salvage neck dissections is associated with reduced survival. Radiotherapy alone, human papillomavirus negative cancer and increase in lymph node size, are associated with viable tumor in salvage neck dissections. In case of decreased or stable lymph node size after chemoradiation, watchful waiting could be considered.

Prognostic factors for tube feeding dependence after curative (chemo-) radiation in head and neck cancer: A systematic review of literature.

BACKGROUND: Tube feeding dependence is a commonly observed debilitating side-effect of curative (chemo-) radiation in head and neck cancer patients that severely affects quality of life. Prevention of this side-effect can be obtained using advanced radiation techniques, such as IMRT. For radiotherapy treatment plan optimization, it has become increasingly important to develop prediction models that enable clinicians to predict the risk of tube feeding dependence for individual patients. To develop such a tool, information regarding the most relevant prognostic factors for tube feeding dependence is necessary. OBJECTIVES: The primary aim of this systematic review, conducted according to PRISMA guidelines, was to identify prognostic factors that are consistently found to be associated with tube feeding dependence at ≥6months after treatment. The secondary aim was to identify prognostic factors found to be associated with tube feeding placement and use at <6months. DATA SOURCES: Articles were identified through a search in MEDLINE, EMBASE and the Cochrane Library. Approximately 2600 articles were screened and selected by inclusion and exclusion criteria. RESULTS: Fourteen retrospective studies were identified that fulfilled the inclusion criteria and reported on prognostic factors for tube feeding dependence at ≥6months. The studies reported on patient and disease variables, treatment variables and DVH parameters. Two of these studies reported on a model for tube feeding dependence, one including DVH parameters. Additionally, 18 studies were identified that reported on prognostic factors for tube feeding placement and use at <6months. CONCLUSIONS: Prognostic factors that were consistently associated with the risk of tube feeding dependence at ≥6months for head and neck cancer patients treated with (chemo-) radiotherapy were DVH parameters, including dose to the larynx, the pharyngeal constrictor muscle inferior and superior, and the dose to the contralateral parotid gland. Furthermore, advanced tumor and nodal stage, pretreatment weight loss, (concomitant) chemotherapy and prophylactic gastrostomy policy were prognostic for tube feeding dependence ≥6months. For tube feeding use at less than 6months, prognostic DVH parameters included dose and volume to the oral mucosa, dose to the contralateral submandibular gland, and also dose to the larynx and the pharyngeal constrictor muscle inferior and superior. Prognostic patients/disease and treatment factors for tube feeding placement and use at less than 6months were similar to the prognostic factors for tube feeding dependence at ≥6months, but also included several unique variables such as the use of narcotics prior to treatment and living alone at the time of treatment.

Multivariable normal tissue complication probability model-based treatment plan optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck radiotherapy.

BACKGROUND AND PURPOSE: Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD). MATERIALS AND METHODS: One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OFDYS and OFTFD-plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OFNTCP-based plans. RESULTS: All OFNTCP-based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OFDYS-plan, OFTFD-plan, and clinical plan. For 5% of patients NTCPTFD reduced >5% using OFTFD-based planning compared to the OFDYS-plans. CONCLUSIONS: Plan optimization using NTCPDYS- and NTCPTFD-based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OFTFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCPTFD values as compared to the other studied plans.

Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The current knowledge about potential risk factors for lymph node (LN) metastasis in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) is primarily based on studies that lack adjustment for confounding variables. OBJECTIVES: We sought to identify independent risk factors for LN metastasis in patients with HNcSCC and to evaluate the impact of LN metastasis on prognosis. METHODS: Patients with primary HNcSCC were retrospectively included. Potential risk factors were analyzed by univariate and multivariate Cox regression models. Survival was compared using the Kaplan-Meier method. RESULTS: Three hundred thirty-six patients with 545 primary HNcSCCs were included. The median follow-up period was 43 months (range, 1-176 months). LN metastasis occurred in 55 patients (16.4%). The following independent risk factors of HNcSCC for the development of LN metastasis were identified: location on the ear, tumor diameter >50 mm, moderate and poor differentiation, and tumor thickness >2 mm. There was a significant decline in disease-specific survival and overall survival in patients with LN metastasis compared to patients without LN metastasis. LIMITATIONS: The retrospective study design. CONCLUSION: LN metastases from HNcSCC are common with diminished survival rates. This study confirmed some well-known risk factors, but also found moderate differentiation as an independent risk factor for LN metastasis.

Selection of head and neck cancer patients for adaptive radiotherapy to decrease xerostomia.

BACKGROUND AND PURPOSE: The aim of this study was to develop and validate a method to select head and neck cancer patients for adaptive radiotherapy (ART) pre-treatment. Potential pre-treatment selection criteria presented in recent literature were included in the analysis. MATERIALS AND METHODS: Deviations from the planned parotid gland mean dose (PG ΔDmean) were estimated for 113 head and neck cancer patients by re-calculating plans on repeat CT scans. Uni- and multivariable linear regression analyses were performed to select pre-treatment parameters, and ROC curve analysis was used to determine cut off values, for selecting patients with a PG dose deviation larger than 3Gy. The patient selection method was validated in a second patient cohort of 43 patients. RESULTS: After multivariable analysis, the planned PG Dmean remained the only significant parameter for PG ΔDmean. A sensitivity of 91% and 80% could be obtained using a threshold of PG Dmean of 22.2Gy, for the development and validation cohorts, respectively. This would spare 38% (development cohort) and 24% (validation cohort) of patients from the labour-intensive ART procedure. CONCLUSIONS: The presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources.

Swallowing sparing intensity modulated radiotherapy (SW-IMRT) in head and neck cancer: Clinical validation according to the model-based approach.

PURPOSE: The aim of this study was to clinically validate a multivariable normal tissue complication probability (NTCP) model for grade 2-4 swallowing dysfunction at 6months after radiotherapy or chemoradiation (SWALM6) in head and neck cancer patients treated with swallowing sparing intensity modulated radiotherapy (SW-IMRT) and to test if SW-IMRT resulted in a reduction of the prevalence of SWALM6. MATERIALS AND METHODS: The primary endpoint was SWALM6. For all 186 patients, a standard IMRT (parotid sparing) and a SW-IMRT plan (additional constraints for swallowing organs at risk) was created. The difference in NTCP for SWALM6 (ΔNTCPSWALM6=NTCPstandard-NTCPSW-IMRT) was calculated. Patients were treated with SW-IMRT. The external validation of the NTCP model was analyzed by comparing performance measures. RESULTS: The mean ΔNTCPSWALM6 was 4.9% (range 0.01-17.3%), with a significant lower mean predicted NTCPSW-IMRT of 22.6% (95% CI 20.2-24.9%), compared to NTCPstandard of 27.5% (95% CI 24.9-29.9%) (p<0.001). There was a perfect correspondence of NTCPSW-IMRT with the observed prevalence of SWALM6 (22.6%). The overall model performance, discrimination and 'goodness of fit' were good. CONCLUSION: We externally validated the multivariable NTCP model for SWALM6 in SW-IMRT treated patients, showing reduced swallowing dysfunction by reducing the dose parameters included in this NTCP model.

Patterns of long-term swallowing dysfunction after definitive radiotherapy or chemoradiation.

OBJECTIVES: To identify patterns of long-term, radiation-induced swallowing dysfunction after definitive radiotherapy with or without chemotherapy (RT or CHRT) and to determine which factors may explain these patterns over time. MATERIAL AND METHODS: The study population consisted of 238 consecutive head and neck cancer patients treated with RT or CHRT. The primary endpoint was ⩾grade 2 swallowing dysfunction at 6, 12, 18 and 24months after treatment. Cluster analysis was used to identify different patterns over time. The differences between the mean dose to the swallowing organs at risk for each pattern were determined by using dose maps. RESULTS: The cluster analysis revealed five patterns of swallowing dysfunction: low persistent, intermediate persistent, severe persistent, transient and progressive. Patients with high dose to the upper pharyngeal, laryngeal and lower pharyngeal region had the highest risk of severe persistent swallowing dysfunction. Transient problems mainly occurred after high dose to the laryngeal and lower pharyngeal regions, combined with moderate dose to the upper pharyngeal region. The progressive pattern was mainly seen after moderate dose to the upper pharyngeal region. CONCLUSIONS: Various patterns of swallowing dysfunction after definitive RT or CHRT can be identified over time. This could reflect different underlying biological processes.

Multicriteria optimization enables less experienced planners to efficiently produce high quality treatment plans in head and neck cancer radiotherapy.

OBJECTIVES: To demonstrate that novice dosimetry planners efficiently create clinically acceptable IMRT plans for head and neck cancer (HNC) patients using a commercially available multicriteria optimization (MCO) system. METHODS: Twenty HNC patients were enrolled in this in-silico comparative planning study. Per patient, novice planners with less experience in dosimetry planning created an IMRT plan using an MCO system (RayStation). Furthermore, a conventionally planned clinical IMRT plan was available (Pinnacle(3)). All conventional IMRT and MCO-plans were blind-rated by two expert radiation-oncologists in HNC, using a 5-point scale (1-5 with 5 the highest score) assessment form comprising 10 questions. Additionally, plan quality was reported in terms of planning time, dosimetric and normal tissue complication probability (NTCP) comparisons. Inter-rater reliability was derived using the intra-class correlation coefficient (ICC). RESULTS: In total, the radiation-oncologists rated 800 items on plan quality. The overall plan score indicated no differences between both planning techniques (conventional IMRT: 3.8 ± 1.2 vs. MCO: 3.6 ± 1.1, p = 0.29). The inter-rater reliability of all ratings was 0.65 (95% CI: 0.57-0.71), indicating substantial agreement between the radiation-oncologists. In 93% of cases, the scoring difference of the conventional IMRT and MCO-plans was one point or less. Furthermore, MCO-plans led to slightly higher dose uniformity in the therapeutic planning target volume, to a lower integral body dose (13.9 ± 4.5 Gy vs. 12.9 ± 4.0 Gy, p < 0.001), and to reduced dose to the contra-lateral parotid gland (28.1 ± 11.8 Gy vs. 23.0 ± 11.2 Gy, p < 0.002). Consequently, NTCP estimates for xerostomia reduced by 8.4 ± 7.4% (p < 0.003). The hands-on time of the conventional IMRT planning was approximately 205 min. The time to create an MCO-plan was on average 43 ± 12 min. CONCLUSIONS: MCO planning enables novice treatment planners to create high quality IMRT plans for HNC patients. Plans were created with vastly reduced planning times, requiring less resources and a short learning curve.