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Purpose This study was aim to evaluate the patterns of failure according to radiotherapy (RT) target volume for cervical lymph nodes in metastases of unknown primary origin in head and neck region (HNMUO). Materials and Methods Sixty-two patients with HNMUO between 1998 and 2016 were retrospectively reviewed. We analyzed the clinical outcomes and primary site failure depending on the radiation target volume. The target volume was classified according to whether the potential head and neck mucosal sites were included and whether the neck node was treated involved side only or bilaterally. Results Potential mucosal site RT (mucosal RT) was done to 23 patients and 39 patients did not receive mucosal RT. Mucosal RT showed no significant effect on overall survival (OS) and locoregional recurrence (LRR). The location of primary site failure encountered during follow-up period was found to be unpredictable and 75% of patients with recurrence received successful salvage therapies. No significant differences in OS and LRR were found between patients treated to unilateral (n = 35) and bilateral neck irradiation (n = 21). Treatment of both necks resulted in significantly higher mucositis. conclusions We found no advantages in OS and LRR of patients with HNMUO when mucosal sites and bilateral neck node were included in the radiation target volume.

Purpose We investigated the clinical outcome of sodium alginate treatment in radiation-induced pharyngeal mucositis (RIPM) after neck irradiation. Materials and methods The study population included 32 patients (11 lung cancer, 10 breast cancer, 7 head and neck cancer, and 4 other primary lesions) who underwent neck external beam radiotherapy at the authors’ institution between June 2006 and 2016. The patients received 5% sodium alginate solution orally for RIPM. Those who were followed up for less than 2 months or did not receive 5% sodium alginate were excluded from this retrospective study. RIPM was graded weekly as an acute toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4. The administration of 10-15 ml of sodium alginate before each meal was continued until the radiotherapy was completed and after resolution of odynophagia. The efficacy of sodium alginate was assessed by two radiation oncologists as follows: Grade I, ineffective; grade II, moderately effective; grade III, very effective. When sodium alginate was ineffective, other analgesics, such as nonsteroidal anti-inflammatory drugs (NSAIDS) or opioids, were added. Relationships between the presence/absence of additional analgesics and the radiation dose were investigated. Results The median duration from the start of irradiation to sodium alginate administration was 15 days (range, 5–36 days). RIPM improved in 29/32 patients (grade: II, n = 22; III, n = 7). Three patients showed no improvement. No sodium alginate-related toxicities occurred. Additional analgesics were required in 5/32 patients. The radiation dose in these 5 patients was significantly higher than that in the sodium alginate-alone group (63.6 ± 7.8 Gy vs 48.3 ± 14.8Gy, P = 0.02). Patients who received > 50 Gy tended to require additional analgesics more frequently than those who received ≤50Gy (P = 0.10). Conclusions The concurrent administration of sodium alginate and neck irradiation was feasible and tolerable without obvious toxicities. Under certain conditions sodium alginate could be a promising alternative to NSAIDs and opioids in RIPM. The results justify further prospective evaluations with detailed treatment protocols to clarify whether sodium alginate can improve RIPM.

Background/aim: To assess the efficacy and side effects of concurrent weekly chemotherapy and radiotherapy with simultaneous integrated boost (SIB) technique for nasopharyngeal cancer (NPC). Materials and methods: A total of 51 consecutive patients with diagnosis of NPC were treated between February 2010 and December 2015. The median dose for PTV70 (range: 60-82) was given in 33 fractions (range: 31-35). Forty-five of the patients received concomitant weekly chemotherapy between 3-7 cycles (median 6). Eleven patients received neoadjuvant and thirty-nine patients received adjuvant chemotherapy. Results: At a median follow-up 43 months (range: 2-76) the estimated 5-year overall survival and disease-free survival were 74.6% and 62.6%, respectively. Conclusion: In radiotherapy of advanced NPC, generally a considerable amount of normal head and neck tissues might have to be irradiated in addition to gross tumor volume, involved node, and elective neck irradiation. Together with chemoradiotherapy, poor oral hygiene and inadequate nutritional support result in excessive morbidity. Despite loco-regional success of concurrent chemoradiotherapy, distant metastasis is still the major pattern of treatment failure in the intensity modulated radiotherapy era. We need to improve our adjuvant chemotherapy regimens or develop new drugs.

BACKGROUND AND PURPOSE: Among patients undergoing serial neck CTs, we have observed variability in the appearance of the pharyngolaryngeal venous plexus, which comprises the postcricoid and posterior pharyngeal venous plexuses. We hypothesize changes in plexus appearance from therapeutic neck irradiation. The purposes of this study are to describe the CT appearance of the pharyngolaryngeal venous plexus among 2 groups undergoing serial neck CTs—patients with radiation therapy–treated laryngeal cancer and patients with medically treated lymphoma—and to assess for changes in plexus appearance attributable to radiation therapy. MATERIALS AND METHODS: For this retrospective study of 98 patients (49 in each group), 448 contrast-enhanced neck CTs (222 laryngeal cancer; 226 lymphoma) were assessed. When visible, the plexus anteroposterior diameter was measured, and morphology was categorized. RESULTS: At least 1 plexus component was identified in 36/49 patients with laryngeal cancer and 37/49 patients with lymphoma. There were no statistically significant differences in plexus visibility between the 2 groups. Median anteroposterior diameter was 2.1 mm for the postcricoid venous plexus and 1.6 mm for the posterior pharyngeal venous plexus. The most common morphology was “bilobed” for the postcricoid venous plexus and “linear” for the posterior pharyngeal venous plexus. The pharyngolaryngeal venous plexus and its components were commonly identifiable only on follow-up imaging. CONCLUSIONS: Head and neck radiologists should be familiar with the typical location and variable appearance of the pharyngolaryngeal plexus components so as not to mistake them for neoplasm. Observed variability in plexus appearance is not attributable to radiation therapy.

The aim of this study was to assess the effects of neck radiation on the results of Doppler sonography of carotid arteries in head and neck cancer patients.In this prospective, cross-sectional study, 25 consecutive patients with head and neck cancers were assessed for carotid artery stenosis (CAS) by carotid color Doppler sonography before external radiotherapy and six months after external radiotherapy. Main outcome measures were peak systolic velocity (PSVs), end-diastolic velocities (EDVs) of the internal carotid artery (ICA), ICA/common carotid (CCA) ratios, and degree of stenosis.The age of the enrolled patients at the initiation of radiotherapy was 57.9±11.8 years (mean±SD; range, 43-91 years), and only 4 (16%) of the 25 patients were female. The findings showed significant changes in the plaque degree and stenosis degree, and plaque size before and after external radiotherapy (P0.05). Changes in degree of stenosis were significantly correlated with age (p=0.021).After neck irradiation changes in the carotid artery may occur and cause subsequent neurologic events.

Aim of the study To retrospectively assess treatment outcomes among patients treated for salivary gland cancers at our institution to determine which of the three most common treatment approaches - elective neck dissection (END), elective neck irradiation (ENI), or observation - provide the best results. Material and methods A total of 122 patients were identified who had undergone primary surgery for SGC followed by END, ENI, or observation. The patients were classified into three groups according to the treatment approach used to manage the neck: END, ENI, or observation. The main outcome measures were disease-free survival (DFS) and overall survival (OS). We also sought to identify the risk factors potentially associated with neck metastasis and treatment failure. Results 106 patients met all inclusion criteria. Of these 106 patients, 27 (25.7%) underwent END, 17 (16.0%) underwent ENI, and 62 (58.5%) observation. There were no statistically significant differences between the three groups in any of the following variables: advanced age (> 70); presence of locally advanced disease (T3 or T4); perineural invasion; lymphovascular invasion; and primary tumour location. Treatment failure was higher (non-significantly) in the END group (25.9%) vs. the observation (21.0%) and ENI (11.8%) groups. No differences (Kaplan-Meir curves) were observed among the three groups in terms of DFS or OS. Conclusions Our results show that elective neck dissection does not appear to provide any benefit to patients treated for malignant salivary gland cancer. Importantly, these findings contradict most of the currently available research. However, due to methodological differences among the available studies, our findings cannot be compared directly to other studies.

Purpose This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. Materials and methods A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. Results With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. Conclusion The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

Purpose: Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. Method: A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies. Results: Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration. Conclusion: Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery). (C) 2017 Elsevier B.V. All rights reserved.

Objectives To investigate the feasibility of contralateral lower neck sparing intensity modulation radiated therapy (IMRT) for nasopharyngeal carcinoma patients (NPC) with unilateral cervical lymph node metastasis. Materials and methods Retrospective review of 546 patients with unilateral cervical lymph node metastasis treated between November 2009 and February 2012 at one institution. All patients were staged using magnetic resonance imaging and received radical IMRT. Patients were classified into two groups: the inferior border of the negative neck irradiation field only covered Levels III to Va in Group 1; the inferior border covered entire neck down to Levels IV to Vb in Group 2. Results Median follow-up was 49.9 months (range, 1.3–69.2 months). Four-year overall survival (OS:89.3% vs. 88.9%, P = 0.91), disease-free survival (DFS:81.7% vs. 81.0%, P = 0.91), distant metastasis-free survival (DMFS:88.2% vs. 87.9%, P = 0.95), local relapse-free survival (LRFS:96.7% vs. 94.7%, P = 0.70) and nodal relapse-free survival (NRFS: 96.1% vs. 95.9%, P = 0.94) were not significantly different between Group 1 and Group 2. Twenty-two patients developed cervical lymph node relapse; of whom 20/22 (91.0%) developed unilateral relapse within pretreatment positive neck. Only one patient developed out-of-field relapse, though this patient also relapsed within the neck irradiation field (Level II). No clinicopathological feature tested had significant prognostic value for NRFS in multivariate analysis. Conclusions In the IMRT and MRI era, contralateral lower neck sparing IMRT seems to be feasible for NPC patients with unilateral cervical lymph node metastasis.

Previous radical neck dissection and neck irradiation pose considerable operative risks in patients requiring carotid endarterectomy for symptomatic carotid disease. Carotid stenting is an acceptable alternative for these patients but carries a higher risk of cerebrovascular accidents especially in patients with type III aortic arch anatomy. Herein, we present a technically challenging case of a patient with an irradiated neck and a history of radical neck dissection who presented with a symptomatic high-grade left internal carotid artery stenosis in the setting of a type III aortic arch. He was treated via a hybrid approach for carotid artery stenting.

The baroreflex is an important afferent mechanism controlling autonomic functions. As afferent nerves course through the neck, they are susceptible to damage by neck irradiation in head and neck cancer patients. With increased survival of head and neck cancer patients because of improved therapy, the cardiovascular morbidity and mortality in them have become apparent and this is of clinical concern. There are few case reports of baroreflex failure as a chronic sequel to neck irradiation.The present study evaluated the changes in cardio-autonomic tone and postural cardiovascular reflex in neck-irradiated patients.Head and neck cancer patients who had received neck irradiation (n = 15) and healthy controls (n = 15) were evaluated for heart rate variability with time domain analysis of 5 min ECG recording. Postural cardiovascular reflexes were studied with changes in blood pressure and heart rate in the lying to standing test.Our results suggest that there is a reduction in overall time domain measures of heart rate variability and weakened postural reflexes in neck-irradiated patients.Decreased heart rate variability in neck-irradiated patients reflects an independent risk of cardiovascular morbidity. The early detection of cardiovascular impairment in such patients may help healthcare professionals in providing better care. Furthermore, the dose delivered to the carotid sinus should be monitored and restricted.

Background Free fibular flap (FFF) mandible reconstruction is at high risk of complications due to patient comorbidities, microvascular surgery after neck irradiation and intrabuccal exposure. We aimed to describe clinical and microbiological features, management and outcome of osteomyelitis following mandibular reconstruction with FFF. Methods Patients referred to our reference center for an osteomyelitis following FFF reconstruction of the mandible were included in a retrospective cohort. Microbiology was described based on gold-standard samples. Risk factors for treatment failure (infection persistence or relapse, need for additional surgery for septic reason, infection-related death) were assessed by logistic regression and Kaplan-Meier survival curve analysis. Results 48 patients (age, 60.5 [IQR, 52.4–66.6]; 30 males; 62.5%; modified Charlson comorbidity index, 4 [3–5]) were included. Indications for FFF mandible reconstruction were mostly carcinoma (n=27; 56.3%) and osteoradionecrosis (n=12; 25.0%), with 44 (82.9%) previous neck irradiation. FFF osteomyelitis were mostly early (≤ 3 months post-surgery; n=43; 89.6%). Main symptoms were local inflammation (n=28; 59.6%), ununion or sinus tract (n=28; 59.6%), bone or device exposure (n=21; 44.7%), and were associated with radiological signs for infection in 33 (75.0%) cases. Microbiological documentation highlighted Enterobacteriaceae (n=25; 61.0%), Streptococcus spp. (n=22; 53.7%), S. aureus (n=10; 24.4%), anaerobes (n=10, 24.4%), Enterococcus spp. (n=9; 22.0%) and non-fermenting Gram negative bacilli (GNB; n=8; 19.5%). Thirty-nine (81.3%) required surgery, consisting in debridement with implant retention in 25 (64.1%) cases, associated with a 93 (64–128) day course of antibiotherapy. After a follow-up of 18 (11–31) months, 24 (50.0%) treatment failure were observed. An early ID-specialist referral was the only significant predictor of favorable outcome (OR, 0.167; p=0.005). Non-fermenting GNB infections tended to be associated with a higher risk of failure (OR, 8.4; p=0.058). Probability of treatment failure of osteomyelitis following FFF mandible reconstruction according to ID-referral (A), CRP level 2 weeks after surgery (B) and presence of non-fermenting GNB Conclusion Osteomyelitis following mandibular reconstruction with FFF represent difficult-to-treat infections. Our results advocate for a multidisciplinary management, including an early ID-specialist referral. Disclosures All Authors: No reported disclosures

Abstract. A carotid artery pseudoaneurysm in an irradiated neck is a rare entity with possible devastating results and management should be multidisciplinary. We present a successful endovascular treatment of a late carotid artery pseudoaneurysm following patch endarterectomy and cervical radiotherapy.

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.

Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased ( P < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.

Objective: We aim to quantify the magnitude of setup errors in intensity-modulated radiotherapy (IMRT) treated Head and Neck cancer patients and recommend appropriate PTV margin. Methods: 60 patients with head and neck cancer required bilateral neck irradiation were planned and treated by simultaneous integrated boost IMRT technique either treated radically or postoperative. Patients undergoing image-guided radiotherapy (IGRT) each with once weekly scheduled cone beam computed tomography (CBCT). The 3D displacements, systematic and random errors were calculated. The appropriate PTV expansion was determined using Van Herk’s formula. Results: Mean 3D displacement was 0.16 cm in the vertical direction, 0.14 cm in the horizontal direction and 0.16 cm in the longitudinal direction. Conclusion: Use of weekly CBCT allows the planning target volume (PTV) expansion to be reduced according to our setup. The appropriate clinical target volume (CTV)-PTV margin for our institute is 0.30 cm, 0.38 cm, and 0.33 cm in the horizontal, vertical, and longitudinal directions, respectively.

Background: The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted. Methods: PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated. Results: Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p = 0.008), and involvement of midline (p = 0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p = 0.344). Conclusion: The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups. (C) 2017 Elsevier Ltd. All rights reserved

Purpose Nasopharyngeal carcinoma (NPC) is a central tumor with a rich lymphatic network and a propensity for bilateral cervical lymph node metastasis. There is an orderly pattern of lymph node involvement in NPC. There is no current standard for prophylactic neck irradiation in node-negative or limited retropharyngeal (RP) node–positive NPC. This study aims to synthesize the current evidence on upper neck irradiation (UNI) versus whole neck irradiation (WNI) as prophylactic neck irradiation in node-negative or limited RP node–positive NPC. Materials and Methods A search of relevant articles was done from 2000 to October 2015. Critical appraisal and meta-analysis of the eligible studies were undertaken to assess the effectiveness of UNI versus WNI as prophylactic neck irradiation in node-negative or limited involved RP node NPC. Results Only one randomized controlled trial investigated the use of prophylactic UNI versus WNI and showed no confirmed nodal relapse in both arms. Pooled analysis of four retrospective studies showed no significant difference in nodal recurrence, whether in-field or out-of-field recurrence. There was also no significant difference in terms of 5-year distant metastasis–free and overall survival. Conclusion In node-negative or limited RP node–positive NPC, the current evidence shows the possibility of treating only the upper neck (levels II, III, and VA) without compromising nodal control, distant metastasis, and overall survival. As a result of the scarcity of data, more randomized clinical trials are warranted in this subset of patients.

Aims and Objectives: During course of radiation therapy, anatomical variations occur risking overdose of parotid gland. We tried to quantify volume of parotid gland and mean dose to parotid gland after every 10 fractions (#). Materials and Methods: We conducted the prospective study from July 2016 to May 2017 in 25 patients of early-stage oropharyngeal carcinoma. Patients had Karnofsy Performance Score of 80–100, median age was 54 years, and 18 patients were males. Patients were planned with intensity-modulated radiation therapy planning with dose as 66 Gy/30# to planning target volume (PTV) including primary and 54 Gy/30# to PTV-nodal including elective neck irradiation. After each 10#, replanning was done, and variations in parotid volume were studied including Dmean(mean dose to parotids) and D50(the dose delivered to 50% of volume). Other tumor characteristic like PTV of primary was also assessed and minimum PTV volume covered by 95% isodose line was kept as 95%. Results: Average parotid volumes decreased by the mean value of 10% and 6% for the left and right parotids, respectively, and PTV of primary target decreased by mean of 13%. The difference in Dmeandoses to parotid glands was 32% and 42% and difference in D50dose was 30% and 35% on the left and right side, respectively. Conclusions: The parotid volumes differ considerably during adaptive planning done after every ten fractions. These differences in parotid volumes and doses received to parotid glands play a significant role in the risk of xerostomia observed during later follow-up.

Yujiao Li,1,2,* Xiaomin Ou,1,2,* Chunying Shen,1,2 Tingting Xu,1,2 Weiwei Li,1,2 Chaosu Hu1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College, Shanghai, China *These authors contributed equally to the paper Background: To demonstrate the robustness of clinical target volume delineation for nasopharyngeal carcinoma (NPC) patients, this study makes a detailed analysis of the initial irradiated dose of the recurrent site and local failure patterns after intensity-modulated radiation therapy (IMRT). Based on this analysis, further improvement of delineation recommendations may be made in order to improve the quality-of-life in NPC, without decreasing the local control and survival rate. Methods: In total, 382 newly diagnosed non-metastatic NPC patients were retrospectively enrolled, receiving elective neck irradiation to levels II, III, and VA. For patients with local failure, the location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. The dose of radiation received by GTVr (gross tumor volume of recurrence) was calculated and analyzed with dose-volume histogram (DVH). Failures were classified as: “in field” if 95% of GTVr was within the 95% isodose, “marginal” if 20%–95% of GTVr was within the 95% isodose, or “outside” if less than 20% of GTVr was inside the 95% isodose. Results: With a median follow-up time of 61.3 months, 12 patients developed local recurrence (10 cases available). The 5-year overall survival, local relapse–free survival, regional relapse–free survival, distant metastasis failure–free survival, and disease–free survival were 87.8%, 95.2%, 99.1%, 93.3%, and 82.5%, respectively. Dose conformity with IMRT was excellent, and the recurrence was mainly within 3 years after the first treatment. The dosimetric analysis showed that seven failures were classified as “in-field”, two failures as “marginal”, and only one failure as “out-field”. Most local relapse sites located just the same site of primary tumor and most anatomic sites were at low risk of concurrent bilateral tumor invasion. Conclusions: IMRT with elective neck irradiation provides excellent local control for NPC patients without cervical lymph node metastasis. In-field failures are the main patterns for local recurrence, and the radioresistant subvolumes within the gross tumor volume are needed to be identified. This study proposed suggestions for reduction of target volume during IMRT treatment for NPC patients. Keywords: nasopharyngeal carcinoma, intensity-modulated radiotherapy, patterns of local failure, reduction of clinical target volume

Introduction Baroreceptor damage and hypersensitivity can produce labile autonomic blood pressure control. Neck irradiation for malignancy is a well-known but under-recognised cause of baroreceptor failure. Case presentation We describe a dramatic delayed complication of neck irradiation treatment. Our patient developed recurrent unexplained hypotension and pulseless electrical activity cardiac arrest upon connection to intermittent haemodialysis, which he had previously tolerated uneventfully until exposure to radiotherapy. Conclusion No other cause was identified, and this case thus highlights baroreflex dysfunction as an important differential diagnosis in patients with profound hypotension.

Background The risk for cerebrovascular late effects among childhood cancer survivors is considerable. According to recent studies it is not clear which marker could be reliable for the screening of cerebrovascular diseases among the long-term survivors of childhood cancer. The purpose of this study is to analyse arterial stiffness and intima-media thickness as possible early markers of later occurring stroke in long-term survivors of childhood cancer after neck radiotherapy. Patients and methods Twenty-three patients, treated for Hodgkin disease (HD) in childhood, were included. They had received radiation therapy to the neck with 20–65 (median 30) Gy. Twenty-six healthy controls, matched in age, sex, body mass index, arterial hypertension, smoking history and total cholesterol levels were compared. Highresolution colour-coded duplex sonography and power Doppler sonography of the carotid arteries were performed and intima-media thickness, number and quality of plaques were measured. Arterial stiffness indices were calculated. Results Plaque deposits and/or arterial wall calcinations were found in 24 out of 43 (55.8%) irradiated vessels in cancer survivors group and 0 out of 52 vessels in the group of healthy controls (p < 0.01). We found significant group differences for all the stiffness parameters we used (P < 0.05), but there was no difference in intima-media thickness between cases and controls (p = 0.92). In a multivariate model, carotid pulse wave velocity was positively associated with smoking. Conclusions The arterial stiffness has appeared as a possible surrogate marker for stroke in long-term survivors of childhood cancer. Smoking habit might have an additional negative influence on vascular aging in the group of patients after neck radiotherapy.

According to the 2011 and the 2014 updated American Heart Association/American Stroke Association Guidelines, carotid artery stenting (CAS) is indicated as an alternative to carotid endarterectomy (CEA) for the management of symptomatic carotid patients. According to these recommendations, CAS is preferred to CEA in symptomatic patients with specific technical, anatomic, or physiological characteristics that render these individuals at "high risk" for surgery (e.g., contralateral carotid occlusion, previous neck irradiation, recurrent carotid stenosis, and so forth). This article presents emerging data suggesting that most of these criteria do not comprise contraindications for CEA. In fact, CEA is associated with similar (or even better) outcomes compared with CAS in many such "high-risk" patients. Based on these results, the indications of CAS in symptomatic patients may need to be reconsidered.

Background Elective neck irradiation of a clinical node-negative (N0) neck in squamous cell carcinoma (SCC) of the maxillary sinus is a controversial issue. Methods A systematic review of electronic databases and a meta-analysis were conducted to clarify the role of elective neck irradiation in patients with SCC of the maxillary sinus and clinical N0 neck. Regional (neck) nodal recurrence was chosen as the primary endpoint. Results Four retrospective studies with a total of 129 patients met the inclusion criteria. The results of the meta-analysis showed that elective neck irradiation reduced the risk of regional nodal recurrence (fixed effects model: odds ratio [OR] = 0.16; 95% confidence interval [CI] = 0.04–0.67; p = .01; random-effects model: OR = 0.17; 95% CI = 0.04–0.76; p = .02) compared to observation. Conclusion This systemic review and first meta-analysis confirmed that elective neck irradiation can significantly reduce the rate of nodal recurrence in patients with N0 SCC of the maxillary sinus. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1823–1828, 2015

Background The purpose of this study was to summarize the treatment outcomes and evaluate the feasibility of partial neck irradiation in patients with nasopharyngeal carcinoma (NPC) with only retropharyngeal lymph nodes (RLNs) metastasis. Methods Between January 2003 and December 2007, 54 patients with NPC who received partial neck irradiation to levels II, III, and VA and 100 patients who received whole neck irradiation were reviewed. Results The 5-year disease free survival (DFS), disease metastasis-free survival, (DMFS) local relapse-free survival (LRFS), and regional relapse-free survival (RRFS) rates were 81.8%, 87.7%, 94.8%, and 98.1%, respectively. The 5-year RRFS and DFS rates for the partial neck irradiation group and whole neck irradiation group were 98.1% versus 98.0% (p = .882), 87.0% vs 77.0% (p = .117), respectively. Partial neck irradiation was not considered a significant prognostic factor for any endpoint in univariate and multivariate analyses. Conclusion Partial irradiation of neck levels II, III, and VA might be acceptable for patients with NPC with only RLN metastasis. © 2013 Wiley Periodicals, Inc. Head Neck 36: 468–473, 2014

Introduction: Extracranial carotid stenosis, a risk factor for ischemic stroke, is thought to be accelerated by irradiation to the neck region. Nasopharyngeal carcinoma (NPC) has a predilection for East Asian with an incidence of 200-300 annually in Singapore. We studied the prevalence and severity of extracranial carotid disease in patients with prior neck irradiation for NPC, who were at different timepoints from the time of irradiation. Hypothesis: The prevalence of extracranial carotid disease is high among patients with prior neck irradiation, and this may justify a screening programme for early detection and primary stroke prevention. Methods: We conducted a pilot study to examine 50 patients (median age 55.2 years) with prior radiation for NPC with intensity-modulated radiation therapy (IMRT): 26 with =5 years after treatment. All patients received radiation therapy to the neck. Carotid disease was assessed by duplex sonography for severity of stenosis. The European Carotid Surgery Trial (ECST) criteria was employed for assessment for degree of stenosis. Results: Among patients with IMRT >=5 years ago, 25% (6/24) had carotid stenosis of >=50% compared to only 8% (2/26) of patients with IMRT within 5 years. Of these 8 patients with carotid stenosis >=50%, 5 (63%) had plaques with irregular or ulcerated surfaces, which is known to be associated with stroke risk. Based on these preliminary data, the study would require a larger sample size of 100 in each group to be powered at 90% with an alpha of 0.05. All 8 patients with carotid stenosis >=50% from the screening were referred for further evaluation for symptoms and risk factors, and management for secondary stroke prevention. Conclusions: Based on our findings, there is a rationale for screening for carotid disease among patients with prior neck irradiation and the timing of screening is more optimal after 5 years from IMRT. Patients found to have carotid disease should be counselled about risk factor control, antiplatelet medication and possibly carotid intervention for primary stroke prevention.

Previously, we have proposed Erasmus-iCycle, an algorithm for fully automated IMRT plan generation based on prioritised (lexicographic) multi-objective optimisation with the 2-phase ϵ-constraint (2pϵc) method. For each patient, the output of Erasmus-iCycle is a clinically favourable, Pareto optimal plan. The 2pϵc method uses a list of objective functions that are consecutively optimised, following a strict, user-defined prioritisation. The novel lexicographic reference point method (LRPM) is capable of solving multi-objective problems in a single optimisation, using a fuzzy prioritisation of the objectives. Trade-offs are made globally, aiming for large favourable gains for lower prioritised objectives at the cost of only slight degradations for higher prioritised objectives, or vice versa. In this study, the LRPM is validated for 15 head and neck cancer patients receiving bilateral neck irradiation. The generated plans using the LRPM are compared with the plans resulting from the 2pϵc method. Both methods were capable of automatically generating clinically relevant treatment plans for all patients. For some patients, the LRPM allowed large favourable gains in some treatment plan objectives at the cost of only small degradations for the others. Moreover, because of the applied single optimisation instead of multiple optimisations, the LRPM reduced the average computation time from 209.2 to 9.5 min, a speed-up factor of 22 relative to the 2pϵc method.