Defining margins around the Gross Tumour Volume (GTV) to create a Clinical Target Volume (CTV) for head and neck cancer radiotherapy has traditionally been based on presumed knowledge of anatomical ...routes of spread. However, using a concentric geometric expansion around the GTV may be more reproducible. The purpose of this study was to analyse the inter-observer consistency of geometric CTV delineation with adaptation for anatomical boundaries versus anatomically defined CTVs.
Radiation oncologists at four Danish cancer centres delineated high, intermediate and elective dose CTVs (CTV1, CTV2 and CTV3, respectively) in a patient-case template (stage IV squamous cell carcinoma of the oropharynx), first using mainly anatomical margins (original standard) and then using concentric geometric expansion (new standard). Each centre made a dummy-run radiotherapy plan based on the delineated CTVs. The difference between the CTV contours and the radiotherapy plans was evaluated across the centres.
Anatomy-based contours were significantly more heterogenous and showed larger volume differences between centres than geometric margins. Dice similarity coefficient increased by 0.29 and mean surface distance decreased by 4mm for CTV1. Use of consistent CTV volumes resulted in more consistent irradiated volumes between centres.
Introduction of geometric margins resulted in more uniform CTV1 and CTV2 delineation. Geometric CTV expansion was easier, left less room for misinterpretation, and resulted in more uniform treatment plans with similar irradiated high and intermediate dose volumes across all centres.
Abstract Background and purpose HPV is found in head and neck cancer from all sites with a higher prevalence in oropharynx cancer (OPC) compared to non-OPC. HPV/p16-status has a significant impact on ...radiotherapy (RT) outcome in advanced OPC, but less is known about the influence in non-OPC. We analyzed HPV-associated p16-expression in a cohort of patients with stage III–IV pharynx and larynx cancer treated with primary, curatively intended (chemo-)RT, aiming to test the hypothesis that the impact of HPV/p16 also extends to tumors of non-oropharyngeal origin. Material and methods 1294 patients enrolled in previously conducted DAHANCA-trials between 1992 and 2012 were identified. Tumors were evaluated by p16-immunohistochemistry and classified as positive in case of staining in >70% of tumors cells. Results Thirty-eight percent (490/1294) of the tumors were p16-positive with a significantly higher frequency in OPC (425/815) than in non-OPC (65/479), p < .0001. In OPC p16-positivity significantly improved loco-regional control (LRC) (adjusted HR 95% CI: 0.43 0.32–0.57), event-free survival (EFS) (HR 0.44 0.35–0.56), and overall survival (OS) (HR: 0.38 0.29–0.49), respectively, compared with p16-negativity. In non-OPC no prognostic impact of p16-status was found for either endpoint: LRC (HR: 1.13 0.75–1.70), EFS (HR: 1.06 0.76–1.47), and OS (HR: 0.82 0.59–1.16). Conclusions The independent influence of HPV-associated p16-expression in advanced OPC treated with primary RT was confirmed. However, RT-outcome in the group of non-OPC did not differ by tumor p16-status, indicating that the prognostic impact may be restricted to OPC only.
Treatment planning is time‐consuming and the outcome depends on the person performing the optimization. A system that automates treatment planning could potentially reduce the manual time required ...for optimization and could also provide a method to reduce the variation between persons performing radiation dose planning (dosimetrist) and potentially improve the overall plan quality. This study evaluates the performance of the Auto‐Planning module that has recently become clinically available in the Pinnacle3 radiation therapy treatment planning system. Twenty‐six clinically delivered head and neck treatment plans were reoptimized with the Auto‐Planning module. Comparison of the two types of treatment plans were performed using DVH metrics and a blinded clinical evaluation by two senior radiation oncologists using a scale from one to six. Both evaluations investigated dose coverage of target and dose to healthy tissues. Auto‐Planning was able to produce clinically acceptable treatment plans in all 26 cases. Target coverages in the two types of plans were similar, but automatically generated plans had less irradiation of healthy tissue. In 94% of the evaluations, the autoplans scored at least as high as the previously delivered clinical plans. For all patients, the Auto‐Planning tool produced clinically acceptable head and neck treatment plans without any manual intervention, except for the initial target and OAR delineations. The main benefit of the method is the likely improvement in the overall treatment quality since consistent, high‐quality plans are generated which even can be further optimized, if necessary. This makes it possible for the dosimetrist to focus more time on difficult dose planning goals and to spend less time on the more tedious parts of the planning process.
PACS number: 87.55.de
Abstract Background The quality of Volumetric Modulated Arc Therapy (VMAT) plans is highly dependent on the performance of the optimization algorithm used. Recently new algorithms have become ...available which are capable of generating VMAT plans for Elekta accelerators. The VMAT algorithm in Pinnacle3 ® is named SmartArc and its capability to generate treatment plans for head and neck cancer was tested. Methods Twenty-five patients with oropharyngeal or hypopharyngeal carcinoma, previously treated with IMRT by means of Pinnacle3 ® and Elekta accelerators, were replanned with single arc VMAT. The VMAT planning objectives were to achieve clinical target coverage and sparing of the organs at risk (OAR). Comparison with the original clinically used IMRT was made by evaluating (1) dose–volume histograms (DVHs) for PTVs, (2) DVHs for OARs, (3) delivery time and monitor units (MU), and (4) treatment accuracy. Results Equivalent or superior target coverage and sparing of OARs were achieved with VMAT compared to IMRT. Volumes in the healthy tissues receiving between 17.3 Gy and 49.4 Gy were significantly reduced and the conformity (CI95% ) of the elective PTV was improved from 1.7 with IMRT to 1.6 with VMAT. Compared to step-and-shoot IMRT, VMAT reduced the number of MUs by 8.5% to 460 ± 63 MUs per fraction, and delivered on an Elekta Synergy accelerator, the treatment time was on average reduced by 35% to 241 ± 16 s. In Delta4® measurements of the VMAT treatments, 99.6 ± 0.5% of the detector points passed a 3 mm and 3% gamma criterion, identical to the results of IMRT. Conclusions The target coverages obtained in the IMRT and VMAT plans were found to be very similar. SmartArc generated single arc VMAT plans with equivalent or better target coverage and sparing of OARs compared to IMRT, while both delivery time and MUs were decreased. Very good dose accuracy results were obtained delivering the plans on an Elekta accelerator.
The aim was to analyze position of CT-verified local recurrences (LR) and local control (LC) among three centers that used different GTV to CTV1 margins.
In total, 1576 patients completing radical ...primary IMRT for larynx, pharynx, oral cavity HNSCC in three centers in Denmark between 2006 and 2012 were included. CT-verified LRs were analyzed as possible points of recurrence origin and compared between groups of small (0–2.5 mm), larger (>2.5 mm), and anatomical GTV-CTV1 margins. The recurrence point’s position relative to the GTV and 95% prescription dose was evaluated. Overall local control rate was evaluated using Cox uni- and multi-variate analysis.
After a median follow-up of 41 months, 272 patients had local failure. Median GTV-CTV1 margin in Center1, 2 and 3 was 0.0, 3.7 and 9.7 mm, respectively. 51% of local recurrences were inside the GTV. No difference in distribution of LRs in relation to GTV surface (p = 0.4) or the dose to LRs (p = 0.2) was detected between the groups. A difference in LC was found univariate between the centers (p = 0.03), but not in multivariate analysis (p = 0.4).
No relation was found between the recurrences’ distributions as function of the margins used at three centers. In multivariate analysis, local control was not influenced by the centers.
Abstract Purpose Hypoxia is a cause of resistance to radiotherapy, especially in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate18 ...F-fluoroazomycin arabinoside (FAZA) positron emission tomography (PET)/computed tomography (CT) hypoxia imaging as a prognostic factor in HNSCC patients receiving radiotherapy. Material and methods Forty patients with HNSCC treated with radiotherapy (66–76 Gy) were included. Static FAZA PET/CT imaging 2 h post injection was conducted prior to irradiation. The hypoxic volume (HV) was delineated using a tumor-to-muscle value ⩾1.4. In 13 patients, a repetitive FAZA PET/CT scan was conducted during the radiotherapy treatment. Results A hypoxic volume could be identified in 25 (63%) of the 40 tumors. FAZA PET HV varied considerably with a range from 0.0 to 30.9 (median: 0.3) cm3 . The Tmax /Mmed ranged from 1.1 to 2.9 (median: 1.5). The distribution of hypoxia among the Human Papillomavirus (HPV) positive (12/16) and negative (13/24) tumors was not significant different. In the FAZA PET/CT scans performed during radiotherapy, hypoxia could be detected in six of the 13 patients. For these six patients the location of HV remained stable in location during radiotherapy treatment, though the size of the HV decreased. In 30 patients a positive correlation was detected between maximum FAZA uptake in the primary tumor and the lymph node. During a median follow up of 19 months a significant difference in disease free survival rate with 93% for patients with non hypoxic tumors and 60% for patients with hypoxic tumors could be detected. Conclusion This study emphasizes the role of FAZA PET/CT imaging as a suitable assay with prognostic potential for detection of hypoxia in HNSCC.
Purpose
The aims of the present study were to explore pre-treatment predictors of weight loss during radiation treatment only in head and neck cancer (HNSCC) patients and investigate the weight loss ...in patients with or without a feeding tube.
Methods
Retrospectively, weight change during curative radiotherapy was investigated in 476 consecutive HNSCC patients. Independent predictors were identified using multivariate regression analysis with weight loss below or above 5 % as the primary dependent variable.
Results
Baseline BMI, tumor site, and stage predicted weight loss above 5 %. The odds of weight loss above 5 % in patients with BMI >25 were 3.00 ± 0.64 times higher compared with patients with BMI <25 (
p
< 0.0001). Patients with pharyngeal, oral cavity, or supraglottic tumors had 3.12 ± 0.80 times higher odds of weight loss above 5 % compared with glottic cancer patients (
p
< 0.0001), and the odds were 1.68 ± 0.40 times higher in stage III–IV patients compared with stage I–II patients (
p
= 0.03). Seperate analyses revealed that tumor site and stage only predicted weight loss in patients with BMI >25 but not in patients with BMI <25. Patients receiving a feeding tube weighed less than patients without (73.8 vs 78.3 kg) and feeding tube reduced, but did not prevent, weight loss which averaged 6.7 ± 4.7 kg (7.4 ± 4.7 %) compared with 4.7 ± 5.9 kg (5.5 ± 6.0 %) in patients without a feeding tube (
P
< 0.0001).
Conclusion
Pre-treatment BMI, tumor site and stage predicted weight loss above 5 % in HNSCC patients during radiotherapy. BMI should be considered when analyzing weight loss in HNSCC patients receiving curative radiotherapy.
Abstract Background Comorbidity is common in head and neck squamous cell carcinoma (HNSCC) patients due to the etiology of the disease being primarily smoking. The aim of this study was to ...investigate the impact of comorbidity on survival in a national population-based cohort study on 9388 HNSCC-patients treated with radiotherapy (RT), to re-evaluate the prognostic impact of individual diseases within the Charlson Comorbidity Index (CCI), and to develop a revised head and neck comorbidity index (HN-CCI). Material and methods A national cohort of 9388 HNSCC-patients treated with curative intended RT diagnosed from 1992 to 2008 was identified from the DAHANCA-database. Data on comorbidity prior to HNSCC-diagnosis was obtained from the National Patient Registry and adapted to the CCI. Results By dividing the patients into two groups, we tested and validated which type of comorbidities within the CCI affected overall survival (OS) and cancer specific death (CSD). In total, 36% of patients had comorbidity. Six comorbid conditions within the CCI significantly reduced five-year OS probability: congestive heart failure, cerebrovascular disease, chronic pulmonary disease, peptic ulcer disease, liver disease, and diabetes, and based on these conditions the new head and neck specific comorbidity index was developed, the HN-CCI. Comorbidity according to HN-CCI had a highly significant impact on OS, whereas it was not associated with CSD. Chronological age was not associated with increased risk of CSD after controlling for comorbidity. Conclusions Comorbidity is frequent in HNSCC patients and negatively impacts OS. Therefore assessment of comorbidity will be of great importance, both in order to treat/optimize patient’s health before radiotherapy, but also in order to be able to stratify/control for comorbidity in randomized trials to avoid bias. Re-evaluation of the CCI revealed that only six conditions had an impact on survival, and a new modified index to assess comorbidity for HNSCC-patients was developed. The performance of HN-CCI to stratify patients on survival was good and HN-CCI is highly recommended for future assessment of comorbidity and prognostic staging of radiotherapy-treated HNSCC-patients.
We compare outcomes in two large‐scale contemporaneously treated HPV‐positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16‐confirmed ...HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted‐hazard‐ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack‐years, T‐category and N‐category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM‐8T‐categories (T1‐T2: 77% vs 56%), N‐categories (N0‐N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard‐fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT‐alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazole (NIM) and 73% (856) concurrent weekly cisplatin. DAHANCA had shorter overall‐treatment‐time (P < .001), lower gross tumor (66‐68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow‐up was 4.8 years. DAHANCA had higher 5‐year LRF (13% vs 7%, aHR = 0.47 0.34‐0.67), comparable DM (7% vs 12%, aHR = 1.32 0.95‐1.82), but better OS (85% vs 80%, aHR = 1.30 1.01‐1.68). CRT patients had a lower risk of LRF (aHR 0.56 0.39‐0.82), DM (aHR 0.70 0.50‐1.00) and death (aHR 0.39 0.29‐0.52) vs RT‐alone. We observed exemplary outcomes for two large‐scale trans‐Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de‐intensification of treatment for this disease.
What's new?
HPV‐positive oropharyngeal cancer (OPC) represents a unique subgroup which has very different epidemiology, molecular biology, and response to radiotherapy/chemo‐radiotherapy (RT/CRT) than HPV‐negative squamous cell carcinoma of the head and neck (HNSCC). In this study, the authors compared two large cohorts of HPV‐positive OPC, and found significantly better outcomes in patients that routinely received concurrent chemoradiotherapy with cisplatin compared with radiotherapy alone. The authors conclude that these findings underscore the need for a cautious approach to efforts aimed at de‐intensifying treatment for this disease.
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