An experimental setup for proton irradiation of a murine leg model for radiobiological studies.

BACKGROUND: The purpose of this study was to introduce an experimental radiobiological setup used for in vivo irradiation of a mouse leg target in multiple positions along a proton beam path to investigate normal tissue- and tumor models with varying linear energy transfer (LET). We describe the dosimetric characterizations and an acute- and late-effect assay for normal tissue damage. METHODS: The experimental setup consists of a water phantom that allows the right hind leg of three to five mice to be irradiated at the same time. Absolute dosimetry using a thimble (Semiflex) and a plane parallel (Advanced Markus) ionization chamber and Monte Carlo simulations using Geant4 and SHIELD-HIT12A were applied for dosimetric validation of positioning along the spread-out Bragg peak (SOBP) and at the distal edge and dose fall-off. The mice were irradiated in the center of the SOBP delivered by a pencil beam scanning system. The SOBP was 2.8 cm wide, centered at 6.9 cm depth, with planned physical single doses from 22 to 46 Gy. The biological endpoint was acute skin damage and radiation-induced late damage (RILD) assessed in the mouse leg. RESULTS: The dose-response curves illustrate the percentage of mice exhibiting acute skin damage, and at a later point, RILD as a function of physical doses (Gy). Each dose-response curve represents a specific severity score of each assay, demonstrating a higher ED50 (50% responders) as the score increases. Moreover, the results reveal the reversible nature of acute skin damage as a function of time and the irreversible nature of RILD as time progresses. CONCLUSIONS: We want to encourage researchers to report all experimental details of their radiobiological setups, including experimental protocols and model descriptions, to facilitate transparency and reproducibility. Based on this study, more experiments are being performed to explore all possibilities this radiobiological experimental setup permits.

Consistency in contouring of organs at risk by artificial intelligence vs oncologists in head and neck cancer patients.

BACKGROUND: In the Danish Head and Neck Cancer Group (DAHANCA) 35 trial, patients are selected for proton treatment based on simulated reductions of Normal Tissue Complication Probability (NTCP) for proton compared to photon treatment at the referring departments. After inclusion in the trial, immobilization, scanning, contouring and planning are repeated at the national proton centre. The new contours could result in reduced expected NTCP gain of the proton plan, resulting in a loss of validity in the selection process. The present study evaluates if contour consistency can be improved by having access to AI (Artificial Intelligence) based contours. MATERIALS AND METHODS: The 63 patients in the DAHANCA 35 pilot trial had a CT from the local DAHANCA centre and one from the proton centre. A nationally validated convolutional neural network, based on nnU-Net, was used to contour OARs on both scans for each patient. Using deformable image registration, local AI and oncologist contours were transferred to the proton centre scans for comparison. Consistency was calculated with the Dice Similarity Coefficient (DSC) and Mean Surface Distance (MSD), comparing contours from AI to AI and oncologist to oncologist, respectively. Two NTCP models were applied to calculate NTCP for xerostomia and dysphagia. RESULTS: The AI contours showed significantly better consistency than the contours by oncologists. The median and interquartile range of DSC was 0.85 [0.78 - 0.90] and 0.68 [0.51 - 0.80] for AI and oncologist contours, respectively. The median and interquartile range of MSD was 0.9 mm [0.7 - 1.1] mm and 1.9 mm [1.5 - 2.6] mm for AI and oncologist contours, respectively. There was no significant difference in ΔNTCP. CONCLUSIONS: The study showed that OAR contours made by the AI algorithm were more consistent than those made by oncologists. No significant impact on the ΔNTCP calculations could be discerned.

A national repository of complete radiotherapy plans: design, Results, and experiences.

BACKGROUND: Previously, many radiotherapy (RT) trials were based on a few selected dose measures. Many research questions, however, rely on access to the complete dose information. To support such access, a national RT plan database was created. The system focuses on data security, ease of use, and re-use of data. This article reports on the development and structure, and the functionality and experience of this national database. METHODS AND MATERIALS: A system based on the DICOM-RT standard, DcmCollab, was implemented with direct connections to all Danish RT centres. Data is segregated into any number of collaboration projects. User access to the system is provided through a web interface. The database has a finely defined access permission model to support legal requirements. RESULTS: Currently, data for more than 14,000 patients have been submitted to the system, and more than 50 research projects are registered. The system is used for data collection, trial quality assurance, and audit data set generation.Users reported that the process of submitting data, waiting for it to be processed, and then manually attaching it to a project was resource intensive. This was accommodated with the introduction of triggering features, eliminating much of the need for users to manage data manually. Many other features, including structure name mapping, RT plan viewer, and the Audit Tool were developed based on user input. CONCLUSION: The DcmCollab system has provided an efficient means to collect and access complete datasets for multi-centre RT research. This stands in contrast with previous methods of collecting RT data in multi-centre settings, where only singular data points were manually reported. To accommodate the evolving legal environment, DcmCollab has been defined as a 'data processor', meaning that it is a tool for other research projects to use rather than a research project in and of itself.

Target coverage and local recurrences after radiotherapy for sinonasal cancer in Denmark 2008-2015. A DAHANCA study.

PURPOSE: The study aimed to investigate the pattern of failure and describe compromises in the definition and coverage of the target for patients treated with curatively intended radiotherapy (RT) for sinonasal cancer (SNC). METHODS AND MATERIAL: Patients treated with curatively intended RT in 2008-2015 in Denmark for SNC were eligible for the retrospective cohort study. Information regarding diagnosis and treatment was retrieved from the national database of the Danish Head and Neck Cancer Group (DAHANCA). Imaging from the diagnosis of recurrences was collected, and the point of origin (PO) of the recurrent tumour was estimated. All treatment plans were collected and reviewed with the focus on target coverage, manual modifications of target volumes, and dose to organs at risk (OARs) above defined constraints. RESULTS: A total of 184 patients were included in the analysis, and 76 (41%) relapsed. The majority of recurrences involved T-site (76%). Recurrence imaging of 39 patients was evaluated, and PO was established. Twenty-nine POs (74%) were located within the CTV, and the minimum dose to the PO was median 64.1 Gy (3.1-70.7). The criteria for target coverage (V95%) was not met in 89/184 (48%) of the CTV and 131/184 (71%) of the PTV. A total of 24% of CTVs had been manually modified to spare OARs of high-dose irradiation. No difference in target volume modifications was observed between patients who suffered recurrence and patients with lasting remission. CONCLUSION: The majority of relapses after radical treatment of SNC were located in the T-site (the primary tumour site). Multiple compromises with regards to target coverage and tolerance levels for OARs in the sinonasal region, as defined from RT guidelines, were taken. No common practice in this respect could be derived from the study.

Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.

BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Personal innovative approach in radiation therapy of lung cancer- functional lung avoidance SPECT-guided (ASPECT) radiation therapy: a study protocol for phase II randomised double-blind clinical trial.

BACKGROUND: Radiation therapy (RT) plays a key role in curative-intent treatment for locally advanced lung cancer. Radiation induced pulmonary toxicity can be significant for some patients and becomes a limiting factor for radiation dose, suitability for treatment, as well as post treatment quality of life and suitability for the newly introduced adjuvant immunotherapy. Modern RT techniques aim to minimise the radiation dose to the lungs, without accounting for regional distribution of lung function. Many lung cancer patients have significant regional differences in pulmonary function due to smoking and chronic lung co-morbidity. Even though reduction of dose to functional lung has shown to be feasible, the method of preferential functional lung avoidance has not been investigated in a randomised clinical trial. METHODS: In this study, single photon emission computed tomography (SPECT/CT) imaging technique is used for functional lung definition, in conjunction with advanced radiation dose delivery method in randomised, double-blind trial. The study aims to assess the impact of functional lung avoidance technique on pulmonary toxicity and quality of life in patients receiving chemo-RT for lung cancer. Eligibility criteria are biopsy verified lung cancer, scheduled to receive (chemo)-RT with curative intent. Every patient will undergo a pre-treatment perfusion SPECT/CT to identify functional lung. At radiation dose planning, two plans will be produced for all patients on trial. Standard reference plan, without the use of SPECT imaging data, and functional avoidance plan, will be optimised to reduce the dose to functional lung within the predefined constraints. Both plans will be clinically approved. Patients will then be randomised in a 2:1 ratio to be treated according to either the functional avoidance or the standard plan. This study aims to accrue a total of 200 patients within 3 years. The primary endpoint is symptomatic radiation-induced lung toxicity, measured serially 1-12 months after RT. Secondary endpoints include: a quality of life and patient reported lung symptoms assessment, overall survival, progression-free survival, and loco-regional disease control. DISCUSSION: ASPECT trial will investigate functional avoidance method of radiation delivery in clinical practice, and will establish toxicity outcomes for patients with lung cancer undergoing curative chemo-RT. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04676828 . Registered 1 December 2020.

How public health services pay for radiotherapy in Europe: an ESTRO-HERO analysis of reimbursement.

Reimbursement is a key factor in defining which resources are made available to ensure quality, efficiency, availability, and access to specific health-care interventions. This Policy Review assesses publicly funded radiotherapy reimbursement systems in Europe. We did a survey of the national societies of radiation oncology in Europe, focusing on the general features and global structure of the reimbursement system, the coverage scope, and level for typical indications. The annual expenditure covering radiotherapy in each country was also collected. Most countries have a predominantly budgetary-based system. Variability was the major finding, both in the components of the treatment considered for reimbursement, and in the fees paid for specific treatment techniques, fractionations, and indications. Annual expenses for radiotherapy, including capital investment, available in 12 countries, represented between 4·3% and 12·3% (average 7·8%) of the cancer care budget. Although an essential pillar in multidisciplinary oncology, radiotherapy is an inexpensive modality with a modest contribution to total cancer care costs. Scientific societies and policy makers across Europe need to discuss new strategies for reimbursement, combining flexibility with incentives to improve productivity and quality, allowing radiation oncology services to follow evolving evidence.

Ongoing and future clinical trials in particle therapy in the Nordic countries.

In the Nordic countries, as in the rest of the world, particle therapy as a radiotherapy modality, is evolving, albeit the hard evidence for the clinical benefit still is scarce. However, a common goal for the Nordic countries is to include a minimum of 80% of the patients treated with particle therapy into clinical trials. In this paper, we summarize the current status of clinical trials involving particle therapy in the Nordic countries, with an overview of both active and coming trials. So far, one is closed for inclusion and data are being analyzed, seven trials are actively recruiting patients and several more trials are underway. No common Nordic trial has yet been designed, nor is in the planning phase, and the authors will discuss the obstacles as well as the opportunities a common Nordic platform may represent.

Access to radiotherapy among circumpolar Inuit populations.

Cancer is a substantial health burden for Inuit populations, an Indigenous peoples who primarily inhabit the circumpolar regions of Alaska, Canada, Greenland, and Russia. Access to radiotherapy is lacking or absent in many of these regions, despite it being an essential component of cancer treatment. This Review presents an overview of factors influencing radiotherapy delivery in each of the four circumpolar Inuit regions, which include population and geography, health-systems infrastructure, and cancer epidemiology. This Review also provides insight into the complex patient pathways needed to access radiotherapy, and on radiotherapy use. The unique challenges in delivering radiotherapy to circumpolar Inuit populations are discussed, which, notably, include geographical and cultural barriers. Recommendations include models of care that have successfully addressed these barriers, and highlight the need for increased collaboration between circumpolar referral centres in Alaska, Canada, Greenland, and Russia to ultimately allow for better delivery of cancer treatment.

Towards an evidence-informed value scale for surgical and radiation oncology: a multi-stakeholder perspective.

Surgery and radiotherapy, two locoregional cancer treatments, are essential to help improve cancer outcomes, control, and palliation. The continued evolution in treatment processes, techniques, and technologies-often at substantially increased costs-demands for direction on outcomes that are most valued by patients, and the evidence that is required before clinical adoption of these practices. Three recently introduced frameworks-the European Society for Medical Oncology Magnitude of Clinical Benefit Scale, the American Society of Clinical Oncology Value Framework, and the National Comprehensive Cancer Network Blocks-which all help define the value of oncology treatments, were appraised with a focus on their methods and definition of patient benefit. In this Review, we investigate the applicability of these frameworks to surgical and radiotherapy innovations. Findings show that these frameworks are not immediately transferable to locoregional cancer treatments. Moreover, the lack of emphasis on patient perspective and the reliance on traditional, trial-based endpoints such as survival, disease-free survival, and safety, calls for a new framework that includes real-world evidence with focus on the whole spectrum of patient-centred endpoints. Such an evidence-informed value scale would safeguard against the proliferation of low-value innovation while simultaneously increasing access to treatments that show significant improvements in the outcomes of cancer care.

Cone-beam computed tomography (CBCT) for adaptive image guided head and neck radiation therapy.

BACKGROUND: Adaptive (ART) and image guided radiation therapy (IGRT) can improve target coverage and reduce unnecessary irradiation of organs at risk (OAR). The purpose of this study is to report the results of using mid-course imaging and a novel workflow with cone-beam computed tomography (CBCT) surveillance of dose to OAR to trigger adaptive replanning in head and neck radiotherapy. MATERIAL AND METHODS: Impact of radiation therapist (RTT) managed match protocol and mid-course imaging was assessed in two cohorts of consecutive patients receiving RT to the head and neck region, using computed tomography (CT) and CBCT-based dose verification respectively. In the CBCT cohort, patients at high risk of xerostomia received weekly dose surveillance, while low-risk patients received a mid-course CBCT review. For weekly surveillance, predicted total doses to parotid glands, spinal cord and brainstem were calculated. If predicted mean dose to parotid glands increased by >2 Gy or constraints to brainstem or spinal cord were exceeded, replanning was performed. RESULTS: None had replanning triggered by mid-course imaging. In the CBCT cohort, weekly surveillance of 40 patients yielded minimal reduction in mean dose to parotid glands of 0.65 Gy (range0.4-1 Gy ) for three patients. Patients were surveilled averagely 4.5 times during treatment. Time consumption per CBCT/week was 22 min (range 17-38). Number of patients needed to see to achieve any dose reduction to parotid glands was 13 or the equivalent of 22 working-hours. CONCLUSION: The tested dose surveillance algorithm resulted in a minimal dose reduction ( ≤1 Gy) to parotid glands for three of 40 patients. The proposed algorithm and workflow is thus not sustainable. Mid-course dose verification did not provide added benefit and can be safely omitted in the presence of closely monitored daily IGRT. Daily image guidance and match protocol is a safe and efficient method for identifying patients requiring adaptive replanning.

Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis.

BACKGROUND: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. METHODS: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. FINDINGS: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8). INTERPRETATION: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. FUNDING: Institut National du Cancer; and Ligue Nationale Contre le Cancer.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

BACKGROUND: Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. MATERIALS AND METHODS: In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. RESULTS: Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). CONCLUSION: None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Fear of cancer recurrence and unmet needs among breast cancer survivors in the first five years. A cross-sectional study.

BACKGROUND: It is unclear to which degree the services available after end of treatment are sufficient to meet the needs of women treated for breast cancer. The aim of the present study was to identify patient-reported supportive care needs and the prevalence of fear of cancer recurrence (FCR) following end of treatment in women treated for breast cancer. MATERIAL AND METHODS: Using a cross-sectional design, women treated for breast cancer (n = 155; mean age 63) completed questionnaires concerning supportive care needs and FCR. Inclusion criteria were: ≥18 years of age and treated for primary breast cancer at Aarhus University Hospital, Aarhus, Denmark and between three months and five years after diagnosis. Associations between demographic characteristics, clinical factors, side effects, late effects and the two dependent variables, unmet needs (examined with linear regression model), and FCR (examined with logistic regression model) were analyzed. RESULTS: The response rate was 79.9%. Almost all (82.6%) women reported at least one unmet need (mean number 9.3; range 0-34). More than half (59.3%) of the unmet needs were rated as strong unmet needs. The most frequent unmet needs were concerned with doctors collaborate to coordinate care; the need for having ongoing dialog with healthcare providers to receive available local health care services, understandable and up-to-date information, to manage side effects and feeling reassured that the best medical care are given. Having unmet needs were associated with young age, short time since primary surgery, and having clinical FCR. FCR was reported by 54.8% of the women and was associated with short time since primary surgery, having chemotherapy, having unmet needs, and moderate to severe muscle and joint pain and fatigue. CONCLUSIONS: Breast cancer survivors experience substantial unmet needs years after end of treatment, particularly among younger women and women having clinical FCR. Furthermore, FCR is frequent among women, particularly when closer in time to primary surgery.

Analysis of CT-verified loco-regional recurrences after definitive IMRT for HNSCC using site of origin estimation methods.

INTRODUCTION: A significant part of patients with head and neck squamous cell carcinoma (HNSCC) develop recurrent disease after curative radiotherapy. We aimed to analyze loco-regional recurrence pattern by identifying possible points of recurrence origin by three different methods in relation to treatment volumes. MATERIAL AND METHODS: A total of 455 patients completed IMRT-based treatment for HNSCC from 2006 to 2012. A total of 159 patients had remaining cancer after IMRT, developed loco-regional recurrence or distant disease during follow-up. Among those, 69 patients with loco-regional recurrences had affirmative CT or PET/CT scan. Possible points of origin (POs) of the recurrences were identified on scans by two independent observers, estimated as center of mass and as maximum surface distance. The recurrence position was analyzed in relation to high-dose treatment volume (CTV1) and 95% of prescription dose. RESULTS: In total, 104 loco-regional recurrences (54 in T-site and 50 in N-site) were identified in 69 patients. Median time to recurrence for the 69 patients was 10 months. No clinically relevant difference was found between the four POs, with standard deviation between POs in x, y and z axes of 3, 3 and 6 mm. For recurrences inside CTV1, 0-5 mm and 5-10 mm outside CTV1 the standard deviation of dose differences between the POs were 1, 1.4 and 1 Gy, respectively. 56% and 25% of T-site and N-site recurrences were inside CTV1, respectively. Coverage by 95% prescription dose to high-dose treatment volume was achieved in 78% of T-site and 39% of N-site recurrences. CONCLUSIONS: For recurrences identified by possible points of recurrence origin, no significant difference between observer-based or mathematically estimated methods was found. More than half of T-site recurrences were inside high-dose treatment volume, whereas N-site recurrences were mainly outside.

Open source deformable image registration system for treatment planning and recurrence CT scans : Validation in the head and neck region.

BACKGROUND: Clinical application of deformable registration (DIR) of medical images remains limited due to sparse validation of DIR methods in specific situations, e. g. in case of cancer recurrences. In this study the accuracy of DIR for registration of planning CT (pCT) and recurrence CT (rCT) images of head and neck squamous cell carcinoma (HNSCC) patients was evaluated. PATIENTS AND MATERIALS: Twenty patients treated with definitive IMRT for HNSCC in 2010-2012 were included. For each patient, a pCT and an rCT scan were used. Median interval between the scans was 8.5 months. One observer manually contoured eight anatomical regions-of-interest (ROI) twice on pCT and once on rCT. METHODS: pCT and rCT images were deformably registered using the open source software elastix. Mean surface distance (MSD) and Dice similarity coefficient (DSC) between contours were used for validation of DIR. A measure for delineation uncertainty was estimated by assessing MSD from the re-delineations of the same ROI on pCT. DIR and manual contouring uncertainties were correlated with tissue volume and rigidity. RESULTS: MSD varied 1-3 mm for different ROIs for DIR and 1-1.5 mm for re-delineated ROIs performed on pCT. DSC for DIR varied between 0.58 and 0.79 for soft tissues and was 0.79 or higher for bony structures, and correlated with the volumes of ROIs (r = 0.5, p < 0.001) and tissue rigidity (r = 0.54, p < 0.001). CONCLUSION: DIR using elastix in HNSCC on planning and recurrence CT scans is feasible; an uncertainty of the method is close to the voxel size length of the planning CT images.

Failure pattern and salvage treatment after radical treatment of head and neck cancer.

Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal distribution of recurrences, and the outcome of salvage treatment in a contemporary cohort of HNC patients. Methods The study evaluated a cohort of 2062 consecutive patients treated with curative intent at Aarhus University Hospital from 1 January 2000 to 31 December 2013. The database of DAHANCA contained recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T-site (65%) followed by N-site (36%) and M-site (22%). The vast majority of the first recurrences occurred within the first years after primary treatment; 62%, 82%, and 91% within the first, second and third year, respectively. Totally, 51% were amenable for salvage treatment, and 44% benefited from salvage in terms of a complete response. Permanent tumor control was observed in 128 patients (23%) after one or two salvage attempts. The highest salvage rate was recorded in patients with primary glottic carcinoma (41%) and the lowest among hypopharyngeal cancers (2%). Asymptomatic recurrence was recorded in 12% of all recurrences and this was found to be a positive prognostic factor for disease-specific survival, as they had significantly better outcome after salvage. Conclusion Our data support the usefulness of specialized FU in terms of early detection of recurrent disease. In particular patients with silent recurrences benefited from early detection, as they had a significantly lower risk ratio of death from primary HNC.