Neck Fibrosis Research Articles

Quantitative measurements of radiation-induced fibrosis for head and neck cancer: A narrative review.

To provide a comprehensive summary of the different modalities available to measure soft tissue fibrosis after radiotherapy in head and neck cancer patients. PubMed, Scopus, and Web of Sciences. A search was conducted using a list of medical subject headings and terms related to head and neck oncology, radiation fibrosis, and quantitative measurements, including bioimpedance, MRI, and ultrasound. Original research related to quantitative measurement of neck fibrosis post-radiotherapy was included without time constraints, while reviews, case reports, non-English texts, and inaccessible studies were excluded. Discrepancies during the review were resolved by discussing with the senior author until consensus was reached. A total of 284 articles were identified and underwent title and abstract screening. Seventeen articles had met our criteria for full-text review based on relevance, of which nine had met our inclusion criteria. Young's modulus (YM) and viscoelasticity measures have demonstrated efficacy in quantifying neck fibrosis, with fibrotic tissues displaying significantly higher YM values and altered viscoelastic properties such as increased stiffness rate-sensitivity and prolonged stress-relaxation post-radiation. Intravoxel incoherent motion offers detailed insights into tissue changes by assessing the diffusion of water molecules and blood perfusion, thereby differentiating fibrosed from healthy tissues. Shear wave elastography has proven to be an effective technique for quantifying radiation-induced fibrosis in the head and neck region by measuring shear wave velocity. There are various modalities to measure radiation-induced fibrosis, each with its unique strengths and limitations. Providers should be aware of these implications and decide on methodologies based on their specific clinical workflow. Step 5.

Quantifying Neck Fibrosis: Establishing the Domain Structure of the Neck Fibrosis Scale.

We recently described the development of the Neck Fibrosis Scale (NFS). In this submission, we confirm domain structure and validate a scoring system for the NFS. Prospective cross-sectional study. Between January 2020 and December 2021, 127 head and neck cancer patients with varying degrees of cutaneous neck fibrosis completed the original 15 item NFS. Exploratory factor analysis was used to identify optimal groupings with similar underlying factors. The association between the domains of the NFS and various measures of neck morbidity (i.e., construct validity) were assessed using gamma regression. Exploratory factor analysis confirmed 13 of the 15 items from the NFS mapped onto two factors, which were labelled 'physical' and 'emotional' domains. Of the remaining two items, 'energy' did not load uniquely onto one factor and was removed. 'Neck-swelling' did not load on either factor (loadings <0.3) but was retained within the physical domain based on clinical importance. This resulted in a revised 14-item questionnaire. Internal consistency for these two domains was high (>0.8, p < 0.01). Both the physical and emotional domains of the revised NFS show strong correlation with the neck dissection impairment index and neck range of motion. The physical domain strongly correlated with neck elasticity (0.902 [95%CI 0.839-0.972], p < 0.01). Patients receiving multimodal therapy had physical domain scores that were 31.6% [95% 13.9-51.8] higher (worse) than unimodal therapy patients. A domain structure and scoring strategy have been developed for the NFS. Future efforts should be directed toward an evaluation of responsiveness. NA Laryngoscope, 133:2198-2202, 2023.

Epidemiology and treatment of head and neck malignancies in the AYA generation.

The Adolescent and Young Adult (AYA) population refers to the population of young adults and adolescents in the 15-39years age group. This population subgroup experiences various important life events. Head and neck malignancies are rare tumors, in general, but they are extremely rare in the AYA population. When analyzed by the primary site of the tumors, thyroid gland, soft tissue, and nasopharyngeal malignancies are the most commonly encountered head and neck malignancies in the AYA generation. The most common histopathologic subtypes are carcinomas (thyroid carcinoma, nasopharyngeal carcinoma) and rhabdomyosarcoma. Therefore, in this review, the author discusses these three diseases in the AYA population in detail. Especially, patients with parameningeal rhabdomyosarcoma are at a high risk of dysfunction and facial deformity. Infertility problems may also occur as long-term sequelae of chemotherapy in this population. Radiation therapy might be associated with considerable morbidity. Complications such as cataract, xerostomia, hearing loss, neck fibrosis, and trismus are also common. Head and neck surgeons and medical oncologists should choose the optimal treatment taking into account the curability of the tumors relative to the long-term adverse events of treatment use. Finally, little evidence has been accumulated on head and neck malignancies in the AYA population, and it is urgently necessary to build a high level of evidence for the future.

Limited Toxicity of Hypofractionated Intensity Modulated Radiation Therapy (H-IMRT) for Head and Neck Cancer

Hypofractionated intensity modulated radiation therapy (H-IMRT) is uncommonly used in head and neck cancers due to concern for toxicity. This study reviews our experience using H-IMRT for head and neck cancers and explores its tolerability and efficacy.This single institution IRB approved retrospective study includes patients with head and neck cancers treated with definitive or post-operative H-IMRT from 2011-2020. Patients treated with ≥50Gy in 20 fractions to the primary tumor site and/or neck with at least 3 months of follow up were included. Patients treated to a superficial target only without proximity to mucosal surfaces or coverage of the elective neck (e.g., scalp; skin only targets) were excluded. Patients undergoing re-irradiation were excluded. Toxicity was scored using CTCAE v4.0. Acute toxicity included events occurring within 90 days of H-IMRT completion. Late toxicities occurred any time thereafter. Multiple toxicities in the same patient were scored separately.Fifty-nine patients with a median follow up of 10.9 months (range 3.0-111.5) were included. The majority of patients were white (93%) and male (78%) with a median age of 79.1. The most common primary tumor sites were skin (42%), major salivary glands (22%), and oral cavity (9%). The most frequent histologies included squamous cell carcinoma (66%) followed by thyroid cancer (7%), melanoma (5%), and Merkel cell carcinoma (5%). Treatment was delivered post-operatively in 80% and definitively in 20% of patients. All patients were treated with ≥50 Gy in 20 fractions, with the most common dose being 50 Gy (53%) followed by 55 Gy (44%). In 64% of patients a secondary elective dose of 45-50 Gy was used. Site treated included primary tumor site/bed with unilateral neck (54%), primary tumor site/bed with bilateral neck (19%), primary tumor site/bed alone (14%), unilateral neck (8%), and bilateral neck (5%). Five patients (8%) experienced a locoregional failure at a median time of 5.4 months (range 2.8-13.9). There were no grade 4 or 5 toxicities. Ten patients (17%) experienced acute grade 3 toxicity including mucositis (12%) and dermatitis (5%). Forty-six patients (78%) had an acute grade 2 toxicity, most commonly dermatitis (41%), pain (32%), fatigue (32%), dysgeusia (31%) and xerostomia (22%). Five patients (8%) experienced grade 2 late complications including neck fibrosis in three patients and trismus, aspiration pneumonia, and osteoradionecrosis in one patient each. No patient experienced grade 3 or higher late toxicity. No patients required the placement of a feeding tube or tracheostomy.Hypofractionated IMRT in the definitive or post-operative treatment of head and neck cancers using ≥50Gy in 20 fractions appears safe and well tolerated with modest toxicity. Prospective studies comparing the safety and efficacy of H-IMRT to conventionally fractionated IMRT are warranted.

Quantifying Neck Fibrosis and Its Functional Implications: Development of the Neck Fibrosis Scale.

Despite increasing recognition of the importance of functional outcomes for patients with head and neck cancer, post-treatment neck fibrosis remains poorly understood. We sought to develop and validate a patient reported outcome measure for head and neck cancer patients with neck fibrosis. Prospective multiphase cross-sectional study. To guide instrument development, we employed the World Health Organization International Classification of Functioning, Disability and Health as our conceptual framework. Items were generated using a composite strategy consisting of patient focus groups, literature review, and expert opinion from a multidisciplinary group. Candidate items were reduced through the item impact method. Preliminary psychometric properties of the finalized instrument were evaluated through measures of internal consistency, test-retest reliability, and construct validity. Four in person focus groups were held with 13 head and neck cancer patients. The process of item generation led to 221 relevant citations and 68 unique items. An additional 17 items were identified from review of existing neck disability questionnaires and expert opinion. A draft instrument with 25 candidate items was generated and reduced to its final 15-item scale using item impact method. Early psychometric testing revealed excellent internal consistency (Cronbach's alpha=0.95) and test-retest reliability [ICC=0.95]. Internal consistency at the item level was good (>0.7) for 11/15 individual items. Four separate constructs were evaluated. Three of the four constructs matched our a priori hypotheses. The Neck Fibrosis Scale demonstrates preliminary reliability and validity for discriminate use. Further research is needed to confirm dimensionality and assess responsiveness. NA Laryngoscope, 132:1015-1021, 2022.

The Impact of Smoking, Alcohol Use, Recurrent Disease, and Age on the Development of Neck Fibrosis in Head and Neck Cancer Patients Following Radiation Therapy.

There is a paucity of information regarding the demographic factors associated with the development of neck fibrosis in head and neck cancer (HNC) patients following radiotherapy. A retrospective review of all patients being treated for HNC at a tertiary care center between 2013 and 2017 was performed. Chi-squared and Mann-Whitney U tests were used to identify differences in incidence and grade of fibrosis, respectively, between populations. A total of 90 patients aged 19 to 99 years were included. Factors associated with an increased incidence of fibrosis included smoking during radiotherapy (p < 0.001), alcohol use (p = 0.026), recurrent disease (p = 0.042), and age less than 60 (p < 0.001) on univariate analysis. Factors associated with increased grade of fibrosis in HNC patients included recurrent HNC (p = 0.033), alcohol use (p = 0.013), patient age younger than 60 years (p = 0.018), smoking during radiotherapy (p < 0.001), and non-Caucasian race (p = 0.012). Identification and intervention directed at patients that possess risk factors associated with fibrosis prior to treatment has the potential to improve the long-term quality of life for HNC patients.

Intensity-modulated radiation therapy with concurrent chemotherapy for head and neck squamous cell carcinomas: Toxicity assessment

Background: Intensity-modulated radiotherapy with concurrent chemotherapy attempt to maintain efficiency while limiting toxicity in the treatment of neck squamous cell carcinomas. Side effects of the therapy are both challenge during treatment such as treatment delay, increasing financial and hospitalization rate and also cause early and late toxicities, affects to patient performances and treatment outcomes. We aimed to assess acute and late toxicity in patients with head and neck squamous cell carcinoma (HNSCC) managed with concurrent chemoradiation therapy using intensity modulated radiation therapy (IMRT) technique. Methods: A prospective descriptive study of 120 patients suffering from non-metastatic HNSCC received Intensity-modulated radiotherapy concurrently with four to six cycles of cisplatin (30mg/m2/day/ weekly) from May 2017 to 2018 at Hue Central Hospital (Vietnam). The dose to the primary tumour and cervical lymph nodes totally taken was 70 Gy. Toxicities were gradedbased on the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG). Results: Acute toxicities were mainly at grade 1 with oral mucositis, dermatitis and nausea/vomiting. For late toxicities, grade 3 xerostomia accountings for 5.8%. Neck fibrosis and trismus were not at grade 3 to grade 4, grade 1 mandibular bone necrosis (3.4%) was found in 3 patients. Conclusions: Concurrent chemoradiation therapy with IMRT demonstrated a well-tolerated regime with manageable toxicities.

Contralateral Lower Neck Sparing Radiotherapy in Stage N1 Nasopharyngeal Carcinoma: Long-Term Survival Outcomes and Late Toxicities.

PurposeTo explore the feasibility of contralateral lower neck sparing radiotherapy for patients with stage N1 nasopharyngeal carcinoma (NPC) by analyzing long-term survival outcomes and late toxicities.MethodsData of patients with stage N1 NPC who were treated with contralateral lower neck sparing radiotherapy between January 2013 and December 2015 were analyzed. These patients were all staged by magnetic resonance imaging (MRI), and all received irradiation to the upper neck (levels II, III, and Va) bilaterally along with ipsilateral levels IV and Vb, without irradiation of the contralateral lower neck. Treatment outcomes, regional failure patterns, and late toxicities were examined.ResultsA total of 275 eligible patients with stage N1 NPC were included in the present study. The median follow-up period was 62 months (range, 3–93 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), locoregional recurrence-free survival (LRRFS), and progression-free survival (PFS) rates were 90.5, 91.3, 94.7, 95.3, 91.2, and 81.7%, respectively. A total of 13 patients (4.7%) developed regional recurrence, all of which occurred in the field and not out of the field. Among 254 patients with available data on late toxicities, the most common late toxicity was xerostomia. No late injuries occurred in the carotid arteries, brachial plexus, or spinal cord. In addition to one case (0.4%) of neck fibrosis and three cases (1.2%) of hearing loss, there were no other grade 3–4 late toxicities observed.ConclusionsContralateral lower neck sparing radiotherapy would be safe and feasible for patients with stage N1 NPC, with the potential to improve the long-term quality of life of patients.

Analysis Of Follow-Up Results Of Chronotherapy And Conventional Chemotherapy Combined With IMRT For Locally Advanced Nasopharyngeal Carcinoma

To compare the long-term side effects and survival rates of Intensity modulated radiation therapy combined with chemotherapy in the treatment of advanced Nasopharyngeal carcinoma, and It is expected to reduce the long-term toxic response without reducing the survival, to find a more reasonable treatment for locally advanced Nasopharyngeal carcinoma. 160 patients with locally advanced nasopharyngeal carcinoma were randomly divided into a Time group and conventional group using a professional statistical randomized list (1:1) for treatment. Time group induced chronotherapy with TPF regimen, docetaxel 75 mg/m2 ivgtt, execution in d1 03:30-04:30. Cisplatin 75mg/m2 civ, completed in 5 days, every day from 10:00 to 22:00.5-FU 750mg/m2/d civ, completed in 5 days, every day from 22:00 to 10:00, 2 cycles/21 day. IMRT combined with cisplatin chemotherapy after 3 weeks of induction chemotherapy 100mg/m2 civ, completed at 10:00-22:00,3cycles/21day.In the conventional group, the conventional TPF regimen chemotherapy docetaxel 75mg/m2 ivgtt starts at 10:00.Cisplatin 75mg/m2 civ, begins after the end of docetaxel.5-FU 750mg/m2/d civ, completed in 5 days, executed 24 hours a day, 2cycles/21day.IMRT combined with cisplatin chemotherapy after 3 weeks of induction chemotherapy 100mg/m2 ivgtt starts at 10:00,3cycles/21day.Observation of long-term toxic and 1,3 years of survival situation. The incidence of hearing loss in the time group and the conventional group was 22.7% vs 39.1%, the incidence of dysphagia was 0% vs 8.6%, and the incidence of neck fibrosis was 4.5% vs 15%. The difference was statistically significant (P<0.05). Results of 1,3-year survival of patients in the two groups: The overall survival of time group and conventional group is 97.0% vs 92.8%、80.3% vs 81.2%,not statistically significant (P>0.05), the progression-free survival of time group and conventional group is 95.50% vs 87.0%、71.2% vs 73.9%,not statistically significant(P>0.05),the local recurrence-free survival of time group and conventional group is 97.0% vs 95.7%、92.4% vs 92.8%, not statistically significant(P>0.05) and the distant metastasis-free survival of time group and conventional group is 97.0% vs 98.6%、90.9% vs 91.3%, not statistically significant(P>0.05) When chronotherapy and intensity modulated radiation therapy were combined, the toxicity and side effects of patients were decreased without decreasing survival. Chronotherapy combined with intensity modulation radiotherapy is a recommended mode in the treatment of locally advanced nasopharyngeal carcinoma.

Tracheo Esophageal Prosthesis Insertion Under Endoscopic Guidance and Local Anaesthesia- Feasibility and Outcome.

Voice rehabilitation after laryngectomy is by tracheo esophageal puncture (TEP) and prosthesis insertion. Secondary TEP is very difficult due to neck fibrosis. Puncture under local anaesthesia with endoscopy guidance is a feasible option. Retrospective review of all laryngectomy patients from March 2009 till March 2019 was done and the methods of voice rehabilitation were assessed. The patients undergoing the procedure were classified according to the timing of insertion and type as primary insertion under general anaesthesia (Group P), secondary insertion under local anaesthesia (Group L), secondary insertion under general anaesthesia (Group G). The speech outcome and the procedure outcome were compared. There were 148 patients who underwent laryngectomy, of which groups P, G, L were 12, 12 and 11. The rate of successful insertion was 100% in primary, 91.6% in secondary in general anaesthesia and 91% in secondary under local anaesthesia. All secondary TEP were done after surgery and radiotherapy. Complications related to the insertion techniques were minimal. Speech outcome were similar on intelligibility rating scale and longevity was not affected by the method. TEP in local anaesthesia is feasible and has comparable outcome with TEP in general anaesthesia. Financial burden was very much less in group L compared to the other two groups.

Chimioradiothérapie concomitante des cancers des voies aérodigestives supérieures. Faut-il revoir les contraintes de dose dans les organes à risque ?

Concurrent chemoradiotherapy improves the outcome of locally advanced head and neck cancers and the current reference chemotherapy is cisplatin. These results are obtained at the cost of increased toxicities. To limit the risk of toxicity, organ at riskdose constraints have been established starting with 2D radiotherapy, then 3D radiotherapy and intensity-modulated radiotherapy. Regarding grade ≥3 acute toxicities, the scientific literature attests that concurrent chemoradiotherapy significantly increases risks of mucositis and dysphagia. Constraints applied to the oral mucosa volume excluding the planning target volume, the pharyngeal constrictor muscles and the larynx limit this adverse impact. Regarding late toxicity, concurrent chemoradiotherapy increases significantly the risk of postoperative neck fibrosis and hearing loss. However, for some organs at risk, concurrent chemotherapy appears to increase late radiation induced effect, even though the results are less marked (brachial plexus, mandible, pharyngeal constrictor muscles, parotid gland). This additional adverse impact of concomitant chemotherapy may be notable only when organs at risk receive less than their usual dose thresholds and this would be vanished when those thresholds are exceeded as seems to be the situation for the parotid glands. Until the availability of more robust data, it seems appropriate to apply the principle of delivering dose to organs at risk as low as reasonably achievable.

A predictive model of radiation-related fibrosis based on the radiomic features of magnetic resonance imaging and computed tomography.

BackgroundTo establish a predictive model for the fibrotic level of neck muscles after radiotherapy by using radiomic features extracted from the magnetic resonance imaging (MRI) before and after radiotherapy and planning computed tomography (CT) in nasopharyngeal carcinoma patients.MethodsA total of one hundred and eighty-six patients were finally enrolled in this study. According to the specific standard, all patients were divided into three different fibrosis groups. Regions of interests (ROI), including sternocleidomastoids (SCMs), trapezius (T), levator scapulae (LS), and scalenus muscles (S), were delineated manually and used for features extraction on IBEX. XGBoost, a machine learning algorithm, was used for the establishment of the prediction model. First, the patients were divided into training cohort (80%) and testing cohort (20%) randomly. Then the image features of CT or delta changes calculated from pre- and post-radiotherapy MRI images on each cohort constituted training and testing datasets. Then, based on the training dataset, a well-trained prediction model was produced. We used five-fold cross-validation to validate the predictive models. Afterward, the model performance was assessed on the ‘testing’ set and reported in terms of area under the receiver operating characteristic curve (AUC) under five scenarios: (I) only T1 sequence, (II) only T2 sequence, (III) only T1 post-contrast (T1 + C) sequence, (IV) Combination of all MRI sequences, (V) only CT.ResultsMost of the patients enrolled are male (73.1%), mean age was 47 years, receiving concurrent chemo-radiotherapy as the primary treatment (90.9%). By the end of the final follow-up, most of the patients were rated as mild fibrosis (60.8%). We found the prediction model based on the CT image features outperform all MRI features with an AUC of 0.69 and accuracy of 0.65. Contrarily, the model based on features from all MRI sequence showed lower AUC less than 0.5 and lower accuracy less than 0.6.ConclusionsThe prediction model based on CT radiomics features has better performance in the prediction of the grade of post-radiotherapy neck fibrosis. This might help guide radiotherapy treatment planning to achieve a better quality of life.

Analysis of follow-up results of chrono-chemotherapy or conventional chemotherapy combined with intensity modulated radiotherapy in locally advanced nasopharyngeal carcinoma

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Comparison of Long-Term Outcomes and Sequelae Between Children and Adult Nasopharyngeal Carcinoma Treated With Intensity Modulated Radiation Therapy

Our purpose was to compare long-term survival outcomes and sequelae between child and adult nasopharyngeal carcinoma (NPC) in the era of intensity modulated radiation therapy. Data on 285 patients with NPC aged ≤18 years at diagnosis and treated with intensity modulated radiation therapy between January 2004 and November 2016 were retrospectively reviewed. A propensity score matching method was adopted to screen matched adult patients with NPC at a ratio of 1:3. Survival outcomes and treatment-related toxicities between child and adult groups were compared. In total, 159 children and 477 adult patients with NPC were included in this study. The 5-year overall survival, distant metastasis-free survival, locoregional relapse-free survival, and disease-free survival between children and adults were 89.2% versus 83.6% (P = .144), 88.7% versus 83.5% (P = .124), 96.4% versus 89.1% (P = .013), and 86.5% versus 77.3% (P = .021), respectively. Subgroup analyses revealed that the young age was an independent prognostic factor of overall survival, distant metastasis-free survival, and locoregional relapse-free survival in the advanced N stage (N2-3) group and disease-free survival in the advanced T stage (T3-4) group and N2-3 and stage III-IVA groups. The most common sequela was ototoxicity (68.9%) in child patients and xerostomia (70.8%) in adult patients. Adult survivors had a significantly higher incidence of grade 3 to 4 late toxicities in xerostomia (17.6% vs 8.9%; P = .004), skin dystrophy (9.3% vs 3.7%; P = .022), neck fibrosis (8.3% vs 4.4%; P < .001), and radiation encephalopathy (0.8% vs 0; P = .006). Child survivors were more likely to develop grade 3 to 4 growth retardation and endocrine insufficiency (3.0% vs 0.3%; P = .014). Child patients with NPC achieved significantly better survival outcomes but fewer late toxicities than adult patients. However, we should pay great attention to growth problems of child survivors.

A Predictive model of radiation-related fibrosis based on radiomic features of Magnetic Resonance Imaging

Radiation-related fibrosis of normal tissues remains unpredictable. To predict the fibrotic level of neck muscles after radiotherapy, we established a predictive model by using the magnetic resonance imaging (MRI) before and after radiotherapy based on Radionics in nasopharyngeal carcinoma patients. A total of three hundred and seven patients who received radical radiotherapy at a single institution were enrolled in this study. Patient's clinical were recorded systematically. The median follow-up time is 18 months (range, 11-22 months). According to the symptoms and physical signs, all patients were divided into two groups, the mild fibrosis group, and the severe fibrosis group. All MRI images included three sequences: T1 weighted scans, T2 weighted scans, and contrast-enhanced T1 weighted scans. Regions of interests (ROI), were delineated manually on an open infrastructure software platform, including sternocleidomastoids (SCMs), trapezius (T), levator scapulae (LS), and scalenus (S) muscles. The ROIs were divided into two parts by the level of the cricoid cartilage. The dose distribution was matched to each ROI individually via a software program, Min, Max, and Mean dose parameters were collected afterwards. One hundred ninety features were extracted via the software platform from pre- and post-radiotherapy images. The magnitude of change of each feature was computed as ‘delta change= [post-pre]/pre and then correlated to the grade of neck fibrosis using a machine learning algorithm, XGBoost. First, the image features delta changes with label information were both divided into training and testing sets. Then, based on the training dataset, a well-trained prediction model was provided by XGBoost. Afterward, the predictive model performance was assessed on the ‘testing’ set and reported in terms of area under the receiver operating characteristic curve (AUC). Most of the patients enrolled are male (73.6%), mean age was 47 years, locally advanced stage (89.3%), receiving concurrent chemo-radiotherapy as the primary treatment (90.6%). By the end of the final follow-up, most of the patients were rated as mild fibrosis (85.6%). We found that the image features from T1+C modality outperformed all the other feature combinations in terms of the prediction accuracy, with an AUC of 0.61. The prediction model based on radiomics features from T1+C modality have the best performance in prediction of the grade of severity of post-radiotherapy neck fibrosis. This might help to guide radiotherapy treatment planning and organs at risk sparing for the better quality of life outcomes.Abstract 3389; Table 1The categorization of muscle fibrosis on the neck after treatment among 307 patientsLevelConditionsMild1. Self-Rating: 0-4 points2. No facial edema3. No upper limb pains4. Neck activity is unrestrictedSevere1. Self-Rating: 5-10 points2. Facial edema3. Upper limb pains4. Neck activity is limited Open table in a new tab

Very late xerostomia, dysphagia, and neck fibrosis after head and neck radiotherapy.

Acute and late toxicity after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) impacts on patient quality of life; yet, very late toxicity data remain scarce. This study assessed dysphagia, xerostomia, and neck fibrosis 3-8 years after IMRT. A retrospective analysis using generalized estimated equations was performed on 60 patients with HNC treated with fractionated IMRT between 2000 and 2015 who had a follow-up ≥8 years. Toxicity was scored using LENT-SOMA scales. A trend towards a nonlinear global time effect (P = .05) was noted for dysphagia with a decrease during the 5 years post-treatment and an increase thereafter. A significant decrease in xerostomia (P = .001) and an increase in neck fibrosis (P = .04) was observed until 8 years. Dysphagia, xerostomia, and neck fibrosis do not appear stable over time and remain highly prevalent in the very late follow-up. Our findings support the need for prospective trials investigating very late toxicity in patients with HNC.

Long-term toxicity following radiation therapy for head and neck squamous cell carcinoma: A retrospective study analyzing the effect of concurrent chemotherapy and advanced t-stage on late treatment-induced toxicities.

e17560 Background: There are approximately 436,000 survivors of head and neck squamous cell carcinoma (HNSCC) in the U.S. Toxicities related to definitive chemoradiation or radiation therapy can persist for many years, with some toxicities not presenting clinically until five or more years after definitive treatment. Long-term management of late radiotherapy effects is thus warranted. Methods: This retrospective chart review has three aims: (1) comprehensively assess overall late effects of definitive radiation and chemoradiation; (2) compare treatment-related toxicities between definitive radiation and chemoradiation; and (3) compare treatment-related toxicities between patients with TNM stage T1/T2 tumors to T3/T4 tumors. Late term effects were assessed using 17 toxicity categories including xerostomia, dysphagia, and neck fibrosis. HNSCC patients included in the study were those seen by a single practitioner for follow-up of definitive radiation or chemoradiation, without a history of surgical intervention to the primary site, between June 2017 and June 2018 (N = 49). Results: The median time from the end of treatment to the most recent follow-up was 8.53 years (1.17-24.08 years). In the total cohort, the most common late effect was xerostomia (78%, N = 38), followed by dysphagia (43%, N = 21), and neck fibrosis (27%, N = 13). For the majority of toxicity categories (11 of 17), the cohort that received definitive chemoradiation had higher rates of toxicity than the cohort that received definitive radiation alone. Additionally, for the majority of toxicity categories (10 of 17), the cohort of T3/T4 tumors had higher rates of long-term toxicity than the cohort of T1/T2 tumors. Conclusions: Although the patient population in this study has excellent locoregional control after definitive radiation or chemoradiation, the majority of patients suffer from long-term treatment-related toxicities. Long-term follow up care is needed to manage the late effects of radiotherapy that can develop and persist for years after treatment completion.

Incidence of severe late toxicities of head and neck squamous cell cancer (HNSCC) treatment in the era of intensity modulated radiotherapy (IMRT).

e17570 Background: IMRT for HNSCC limits exposure to critical nearby structures thereby reducing toxicities. Real world data on toxicities after long term follow-up post IMRT for HNSCC are lacking. This study assessed the incidence of late toxicities in patients with HNSCC within 5 years post-treatment with definitive IMRT (d-IMRT). Methods: This is a retrospective, IRB approved, single-institution review of patients (pts) with stage I-IVB HNSCC treated with d-IMRT +/- chemotherapy between 2009 and 2013. The primary outcomes were incidence of severe late toxicities (dysphagia requiring esophageal stricture dilation, physician-reported grade 2 or worse neck fibrosis and xerostomia) occurring 3 months or more after completion of IMRT; feeding tube (FT) dependence within 1st year of IMRT completion, and FT dependence beyond 1st year post IMRT. Toxicities were deemed acute if they occurred during IMRT and up to 90 days post IMRT. Results: 274 pts, median age 59 years (38 – 82.9), were identified. 67.6% were HPV positive, 10.5% HPV negative and HPV status was unknown in 21.9%. Site of disease was oropharynx in 70%, larynx in 25% and hypopharynx in 4%. 206 pts (75.2%) received d-IMRT alone, 37 (13.5%) had definitive concurrent chemoradiation – mostly with cisplatin (58%), and 31 (11.3%) received adjuvant IMRT. Of the 243 pts treated with d-IMRT +/- chemotherapy, 80 (32.9%) required FT during RT due to grade 2 or worse acute dysphagia. Excluding 11 pts with disease recurrence or new HNSCC diagnosis, FT dependence at any time from 3 months to one year post IMRT occurred in 22 of 232 pts (9.48%), while FT dependence beyond 1st year post IMRT occurred in 8 pts (3.4%). 11 pts (4.7%) required stricture dilation for late dysphagia. Late grade 2 or worse fibrosis and xerostomia occurred in 7 (3.0%) and 89 (38.4%) pts, respectively. Conclusions: Our study suggests that except for xerostomia, severe late toxicities after definitive IMRT for HNSCC is likely uncommon. Prospective studies with late IMRT toxicities and their impact on quality of life (QoL) as endpoints are warranted.

Quantitative Evaluation of Shear Wave Elastography on Radiation-Induced Neck Fibrosis in Patients With Nasopharyngeal Carcinoma.

The value of shear wave elastography (SWE) for quantitatively assessing neck fibrosis induced by radiotherapy (RT) in patients with nasopharyngeal carcinoma was evaluated over time. We prospectively observed 56 patients with nasopharyngeal carcinoma before and after therapeutic neck irradiation. The elasticity parameters including Emax and Emean were used to measure the stiffness of the bilateral sternocleidomastoid muscles. Twenty-seven patients completed a 1.5-year follow-up, with examinations beginning at 3, 6, 12, and 18 months after RT. Forty controls were recruited for reliability tests (along with the patients) and measurement comparisons. The consistency of SWE measurements with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic (LENT-SOMA) scale was tested. The intraclass correlation coefficients of elasticity indices for both patients and controls were higher than 0.75. The Emax and Emean of bilateral sternocleidomastoid muscles in the pre-RT patient group were comparable with those of the controls, and increased with increasing postirradiation duration (r = 0.514-0.555; P < 0.01). Significant increases in the Emax and Emean were observed 18 months after RT. The SWE correlated well with the LENT-SOMA score when assessing radiation-induced neck fibrosis 1.5 years after RT (r = 0.557-0.649; P < 0.01). Furthermore, both the Emax and Emean in the LENT-SOMA grade 0 subtype were higher 18 months after RT than before RT (P < 0.01). Because of its high reliability and good consistency with the LENT-SOMA score and better stiffness reflection at grade 0, SWE may be used to objectively and quantitatively evaluate the variation trend of radiation-induced neck fibrosis.

NTENSITY-MODULATED RADIATION THERAPY WITH CONCURRENT CHEMOTHERAPY FOR NASOPHARYNGEAL CARCINOMA

Purpose: To evaluate tumour response, acute and late toxicity in nasopharyngeal cancer (NPC) patients treated with intensity modulated radiotherapy (IMRT) with cisplatin chemotherapy. Materials and Methods: 33 NPC patients, received IMRT concurrently with four to six cycles of cisplatin (30 mg/m2/day) every six weeks between May 2016 and July 2018, were evaluated prospectively. The doses to the planning target volumes of primary tumor and involved lymph nodes, uninvolved regional nodal areas were 70 Gy and 50 Gy respectively. All patients were evaluated for tumour and node response using response evaluation criteria in solid tumour (RECIST) criteri, acute and late toxicities according to CTCAE version 3.0 (common terminology criteria for adverse events), RTOG/EORTC (Toxicity criteria of the Radiation Therapy Oncology Group/the European Organization for Research and Treatment of Cancer). Results: At three months after chemoradiation, 81.8% and 18.2% of patients achieved complete and partial response, respectively. Grade 3 acute toxicities were oral mucositis (6.1%), dermatitis (3%). Grade 3 late toxicities were xerostomia 2/33(6.1%). There was no grade 3 to grade 4 neck fibrosis and trismus, none of the patients developed mandibular bone necrosis. Conclusion:Cisplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. Key words: intensity-modulated radiation therapy, Concurrent chemotherapy and radiation therapy, nasopharyngeal carcinoma