Daan Nevens

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control.

BACKGROUND AND PURPOSE A multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control. MATERIALS AND METHODS Two hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2Gy fractions (NID2Gy) of 50Gy in the standard arm and of 40Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24months using the RTOG scoring system. RESULTS We observed a trend toward less dysphagia at 6months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p=0.01) and 18months (p=0.03). After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40Gy arm vs 14.4% in the 50Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50Gy arm respectively). CONCLUSIONS In our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18months in the 40Gy arm.

The role of stem cells in the prevention and treatment of radiation-induced xerostomia in patients with head and neck cancer

Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation‐induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation‐induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow‐derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study.

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis

PURPOSE To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG2-4) at 6months following R(C)T for HNC. MATERIAL/METHODS 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG2-4 6months after the end of treatment. RESULTS Radiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. CONCLUSION A model for the prediction of fibrosis RTOG2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG2-4 fibrosis at 6months.

Recurrence patterns after a decreased dose of 40 Gy to the elective treated neck in head and neck cancer

PURPOSE To investigate the patterns of regional recurrences with emphasis on recurrences in the electively irradiated lymph node regions after dose de-escalation to 40Gy (EQD2Gy) in head and neck cancer. METHODS AND MATERIALS Two hundred thirty-three patients treated with radio(chemo)therapy using 40Gy (EQD2Gy) to the elective lymph node regions were included. All regional recurrences were reconstructed and projected on the initial radiotherapy planning Computed Tomography studies to identify the localization of recurrence. Furthermore, patient and treatment characteristics were correlated with the regional recurrences to identify risk factors. RESULTS The median follow-up in our study was 26months. Overall- and disease-specific survival at 2years were 71.2% (95% CI 65.3-77.1) and 64.2% (95% CI 59.2-69.3), respectively. Local, regional and distant control at 2years was 84.1% (95% CI 79.1-89.2), 89.2% (95% CI 84.3-94.1) and 83.2% (95% CI 76.3-90.1), respectively. Twenty-eight patients experienced a regional recurrence. Fourteen of these patients had a recurrence within the high dose volume (14 of 28). Nine had a recurrence in the electively irradiated lymph node regions (9 of 28) and 5 recurrences occurred outside the target volume. The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. No significant associations could be observed between recurrence in electively irradiated lymph node regions and age, gender, tumor site, stage, or the presence of human papillomavirus in oropharyngeal cancers. CONCLUSIONS The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. This incidence is comparable to recurrence rates after standard dose of 50Gy, suggesting that lower doses to the elective neck do not result in higher regional recurrences.

Validation of the total dysphagia risk score (TDRS) in head and neck cancer patients in a conventional and a partially accelerated radiotherapy scheme

BACKGROUND AND PURPOSE A risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are most at risk to develop grade ⩾2 dysphagia at 6 months following radiotherapy (RT) for head and neck cancer. The purpose of this study was to validate this model at 6 months and to investigate the power at earlier and later time-points. A second aim was to see if this model can be used in a partially accelerated RT regimen. MATERIALS AND METHODS 164 patients from 3 different centres treated with RT between 2008 and 2014 were included in the current study. Both physician-scored dysphagia and QoL data were prospectively obtained. The TDRS of all patients was correlated with the physician-scored dysphagia and the QoL data. To validate this prediction model, we tested the validity in terms of calibration and discrimination. RESULTS Partial acceleration had no influence on the TDRS. Regarding physician-scored dysphagia, there was a significant correlation with dysphagia grade ⩾2 at 1, 3, 6 and 9 months. The area-under-the-curve at 1 month was 0.85; at 3 months 0.80; at 6 months 0.85; at 9 months 0.86 and 0.79 at 12 months. Regarding QoL, TDRS correlates with PEG-tube usage at 6 and 12 months. CONCLUSION We found significant correlations between TDRS and dysphagia grade ⩾2 and PEG-tube usage.

Upfront vs. no upfront neck dissection in primary head and neck cancer radio(chemo)therapy: Tumor control and late toxicity

PURPOSE/OBJECTIVE The benefit of upfront neck dissection (ND) in locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared disease control and toxicity between patients who were treated with and without upfront ND followed by R(C)T. MATERIAL/METHODS Two-hundred sixty-four consecutive patients with HNSCC without distant metastases at diagnosis and with lymph node stage N2-N3 were included in 2 centers. Patients were all treated between January 2002 and December 2012, and received definitive R(C)T in center 1 and upfront ND followed by R(C)T in center 2. Clinical data and outcome were assessed retrospectively. Toxicity was scored using the LENT-SOMA scale at 6, 12, 18 and 24months following the end of treatment. RESULTS We included 150 patients in the group without ND (center 1) and 114 patients in the group with upfront ND (center 2). Mean follow up was 5.68years in the group without ND and 5.83years in the group with upfront ND. Local, regional and distant control after 2years were 91.07% and 85.96% (p=0.09), 89.22% and 83.27% (p=0.12) and 76.74% and 75.13% (p=0.92) in the group with and without upfront ND, respectively. We did not find a significant difference between both groups regarding edema and atrophy at 6, 12, 18 and 24months. We found a trend at all time-points toward worse outcome in the ND group at all time-points (p=0.06). A significantly higher proportion of moderate to severe fibrosis (grade ≥2) was present in the ND group (p=0.01) at all time points. CONCLUSION There was no significant difference in local, regional or distant control and disease-free survival between both patient populations. Fibrosis, specifically fibrosis grade ≥2 is more prominent following upfront ND and R(C)T when compared to R(C)T alone.

OC-0452: Prospective randomized adaptive dose-de-escalation in the elective neck: late toxicity and control

German Cancer Research Center DKFZ, Heidelberg and German Cancer Consortium DKTK partner site Dresden, Dresden, Germany , F. Lohaus, S. Löck, V. Gudziol, A. Nowak, C. Von Neubeck, I. Tinhofer, V. Budach, A. Sak, M. Stuschke, P. Balermpas, C. Rödel, M. Avlar, A.L. Grosu, A. Abdollahi, J. Debus, C. Belka, S. Pigorsch, S.E. Combs, D. Mönnich, D. Zips, G.B. Baretton, F. Buchholz, M. Baumann, M. Krause

Does the total dysphagia risk score correlate with swallowing function examined by videofluoroscopy

OBJECTIVE The purpose of this study was to correlate the total dysphagia risk score (TDRS) with swallowing function as measured by videofluoroscopy of swallowing using the swallowing performance scale (SPS) and the penetration aspiration scale (PAS). METHODS 63 patients from two different centres treated with radiotherapy for head and neck cancer were evaluated in the current study. Swallowing videofluoroscopies at baseline, 6 and 12 months following radiotherapy were evaluated by two observers. The TDRS of all patients was calculated and correlated with the consensus PAS and SPS scores of the two observers. RESULTS Regarding the PAS scale, we did not observe a significant correlation with the TDRS. Regarding SPS, we found a significant correlation at 6 months (p = 0.01) and a borderline significant correlation at 12 months (p = 0.05). We observed statistically lower SPS scores for patients in the intermediate-risk category when compared to the high-risk category. When we compared low vs high TDRS risk patients, we did not observe a significant difference regarding SPS scores. When comparing low- vs intermediate-risk patients, we observed higher SPS scores in the low-risk group (p = 0.01). When the low- and intermediate-risk patients were grouped together, we observed less swallowing problems as measured by SPS in the low and intermediate group when compared to the high-risk group (p = 0.05) at 6 months. CONCLUSION Patients with high-risk TDRS scores have higher SPS scores when compared to the intermediate group and the intermediate- and low-risk group together. However, low-risk patients in our patient cohort could not be distinguished from high or intermediate-risk patients. Advances in knowledge: TDRS was never correlated with videofluoroscopies in past studies. The hypothesis of this paper was to see if the TDRS could guide us to see which patients are at risk for high scores on SPS and PAS and might need a videofluoroscopic examination in the follow up. Given the poor correlations in our study, however, we cannot recommend the use of the TDRS to select patients who might benefit from the additional information provided by videofluoroscopies.

Can sparing of the superficial contralateral parotid lobe reduce xerostomia following radiotherapy for head and neck cancer

OBJECTIVE The purpose of this study is to see whether sparing the superficial contralateral parotid lobe can help limiting xerostomia following radiotherapy for head and neck cancer. METHODS 88 patients that were included in two prospective randomized studies were analysed in the current study. Using the dosimetry of both the parotid glands, we divided our patients in four groups. Group 1 includes patients where we were able to reduce the radiation dose below the threshold in order to spare both the ipsilateral and contralateral parotid glands, Group 2 consists of patients where only the contralateral parotid gland could be spared. Group 3 consists of patients where only the contralateral superficial parotid lobe could be spared, while in Group 4 not even the contralateral superficial lobe could be spared. RESULTS When we compared Group 1 and Group 2, we did not observe a significant difference between both groups in terms of xerostomia scores at 6 or 12 months. When we compared these groups with Group 3, we observed significant differences with more xerostomia in Group 3 where only the contralateral superficial lobe was spared. A significant difference was also observed between Group 3 and Group 4 with more xerostomia in Group 4. CONCLUSION Sparing of just one superficial parotid lobe results in less xerostomia when compared to not sparing any lobe of both parotid glands. Advances in knowledge: When sparing of the whole contralateral parotid gland is not possible, delineating both the superficial parotid glands and trying to spare at least one of them can mean a way forward in limiting xerostomia in head and neck cancer patients treated with radiotherapy.

EP-1040: Development of a CT-based prognostic model for regional control in head and neck cancer after RT

ESTRO 35 2016 _____________________________________________________________________________________________________ mg/m2 (IRMA 1, 2, 3, 5) or Cetuximab 400 mg/m2 (IRMA 4). A dose of 67.5 Gy in 30 fractions (IRMA 1, 2, and 4) or 70.5 Gy in 30 fractions (IRMA 3, 4, and 5) was delivered to primary tumor and involved nodes, 60 Gy were delivered to high risk and 55.5 Gy to low risk lymph node areas. Static (IMRT) or volumetric (VMAT) intensity modulated technique with simultaneous integrated boost was used.