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ImportanceProton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear.ObjectiveTo report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT.Design, Setting, and ParticipantsThis case series reports a single-institution experience (Memorial Sloan Kettering Cancer Center, New York, New York) between November 2013 and September 2019 and included 122 radiation therapy–naive patients with OOPC treated with PRT. Data were analyzed from 2013 to 2019.Main Outcomes and MeasuresClinical parameters, including sex, age, comorbidities, tumor histology, concurrent chemotherapy, smoking, comorbidities, and preradiation dental evaluation, were obtained from the medical record. Patients with clinical or radiographic signs of ORN were identified and graded using the adopted modified Glanzmann and Grätz grading system. Characteristics of ORN, such as location, clinical presentation, initial stage at diagnosis, etiology, time to diagnosis, management, and clinical outcome at the last follow-up, were also collected.ResultsOf the 122 patients (mean [SD] age, 63 [13] years; 45 [36.9%] women and 77 [63.1%] men) included in this study, 13 (10.6%) developed ORN following PRT during a median (range) follow-up time of 40.6 (Conclusions and RelevanceIn this case series, the prevalence of ORN following PRT was found to be 10.6%, indicating that ORN remains a clinical challenge even in the era of highly conformal PRT. Clinicians treating patients with OOPC with PRT should be mindful of this complication.

This is a unique case report of a 67-year-old female diagnosed with multiple myeloma and extensive use of intravenous bisphosphonate, whose clinical and radiographic presentation of an oral lesion made it challenging to confirm its definitive diagnosis. This patient was referred to the dental service for a suspected medication-related osteonecrosis of the jaw (MRONJ). Clinically, the lesion was located underneath a fixed partial denture in the left posterior mandible. There was a purulent swelling on the lingual side of the fixed partial denture, and a hyperplastic exophytic lesion on the buccal side of the bridge. Panoramic radiograph showed a well circumscribed radiolucent lesion in the left mandible. A biopsy of the gingival lesion on the buccal aspect was inconclusive. As the positron emission tomography scan showed lytic lesions, oral manifestation of multiple myeloma could not be ruled out. A computed tomography-guided biopsy of the left mandible showed plasma cell neoplasm in the histological analysis. Upon confirmed diagnosis, the patient was treated with 20Gy to the left mandible and subsequent debridement of the loose necrotic bone. Following treatment, this gingival lesion resolved completely, and the tumour has remained stable till date.

Intraoral radiation stents (IRS) are prosthetic devices that assist in the effective delivery of radiation to tumor tissues and aim to avoid unnecessary radiation to adjacent healthy tissues, thus limiting postradiotherapy toxicities. They are used to protect or displace vital structures, assist in positioning of the treatment beam for effective administration of radiotherapy, carry a radioactive material, shield healthy tissues of the oral cavity, and/or maintain the desired mouth opening during radiotherapy. With close collaboration between radiation oncologist and oral health care provider, several IRS can be fabricated by the latter for appropriate targeting and delivery of planned radiation dose and optimized treatment results. Modification of these IRS based on individual patient need is recommended to maximize prosthesis utility. The purpose of this review is to discuss the various types of IRS and highlight their clinical utility and benefits in patients receiving radiation therapy in the head and neck cancers.

Precise planning and evaluation of the fibula bone are necessary if immediate endosseous implant placement is considered. Limited information is available on the anatomical dimensions or density of fibula used in mandibular reconstructions. This study aimed to describe the morphology and dimensions of the fibula used to reconstruct segmental mandibular defects and contrast the findings with the native mandible.A retrospective analysis was performed of patients who underwent segmental mandibulectomy reconstructed with osteocutaneous fibula flaps and had at least one postoperative computed tomography scan. Fibula cross sectional dimensions and densities were evaluated with three-dimensional software. Radiographic measurements were obtained from the contralateral mandible medial to the first molar for comparison.Four hundred seventy-seven fibula cross sections from 159 segments were evaluated. Cross-sectional oval, quadrilateral, triangular, and pentagonal shapes differed significantly in proportion (p0.001). Thirty-eight percent of segments (95 percent CI, 30 to 46 percent) had differences in cross-section height greater than 1 mm (p0.001). Between segments within the same patient, the median height difference was 1.58 mm (range, 0.14 to 6 mm). The superior cortex density was significantly higher for the fibula than the native mandible; however, the medullary space density was significantly lower (p0.001).The current study comprises the most comprehensive description of fibula morphology in mandibular reconstructions and highlights the significant variability that exists. The findings provide justification for the added time and cost of computer-aided design and computer-aided manufacturing in centers interested in performing immediate dental implant placement, as the technology provides the necessary precision and accuracy.

Oral cancer treatment involving the maxilla and/or mandible often results in esthetic and functional deficits that can diminish the patient's quality of life. As a result, expeditious reconstruction of the defect and dental rehabilitation is desirable. Dental rehabilitation shortly after reconstruction with an osteocutaneous free flap and resection prosthesis is a persistent challenge for patients with oncologic defects where immediate dental rehabilitation is not a possibility. Additionally, conventional prosthesis fabrication techniques are impractical or impossible due to postoperative anatomical changes and limitations in clinical armamentarium. To address these limitations, a technique and a novel implant-supported prosthetic workflow for the oncologic patient were developed to provide interim dental rehabilitation for such clinical situations. This article describes the prosthesis fabrication technique, reports short-term outcomes, and evaluates patient-reported quality-of-life outcomes using the FACE-Q Head and Neck Cancer Module.

PURPOSE: Dental evaluation and management prior to hematopoietic stem cell transplant (HSCT) plays a vital role in identifying and treating infections that may be life-threatening. The purpose of this study is to describe the dental management of patients undergoing pre-HSCT examination with the Dental Service at Memorial Sloan-Kettering Cancer Center (MSKCC) and to report on odontogenic complications. METHODS: Patients referred for evaluation as part of the standard preparation for HSCT were included. Following clinical and radiological examination, patients were assigned to one of three groups based on risk of odontogenic infection and treatment was provided as indicated. Patients were followed, and their medical records were reviewed for odontogenic complications during the transplant admission. RESULTS: Of the 375 patients evaluated, 350 patients underwent HSCT: Allogeneic 143 (40.9%), Autologous 207 (59.1%). The distribution of primary cancer diagnosis was as follows: multiple myeloma 104 (29.7%), leukemias 95 (27.1%), Hodgkin’s lymphoma 28 (8.0%), Non-Hodgkin’s Lymphoma 99 (28.3%), and other conditions 24 (6.9%). The median time from dental evaluation to transplant was 29 days. The median Decayed, Missing, Filled Teeth Index was 17. The median Community Periodontal Index was 1. Based on dental status, 145 patients (41.4%) were classified as low-risk, 133 (38%) as moderate-risk and 72 (20.6%) as high-risk of odontogenic infection. 114 patients (32.6%) required dental treatment prior to HSCT and 100 of these (28.6%) completed treatment. 2 (0.57%) patients had odontogenic complications. CONCLUSIONS: With conservative pre-HSCT dental treatment based on an infection risk classification system, a low odontogenic complication rate was observed.

Introduction A definitive maxillary obturator prosthesis can be used to rehabilitate a maxillary defect with the aim of improving speech, deglutition, and elimination of oronasal regurgitation. The aims of this study were (1) to determine the time required to fabricate a definitive maxillary obturator prosthesis and (2) to compare the fabrication and follow-up times between a patient's first and second definitive maxillary obturator prosthesis. Materials and methods A retrospective review was completed of patients that had maxillary definitive obturators fabricated following head and neck surgery from 2002 to 2018 (n = 173). Demographics, clinical data, date of surgery, start date of fabrication, follow-up dates, and prosthesis follow-up data were collected. Results The median time to delivery of the patient's first definitive maxillary obturator prosthesis from the date of surgery was 7.7 months for nonradiated patients and 9.6 months for radiated patients (P ≤ .05). Additionally, there was a significant difference in the median number of appointments to fabricate the 1st definitive maxillary obturator prosthesis as compared to the 2nd prosthesis (6 vs 5; P ≤ .05). Conclusion Fabrication timelines differed based on history of radiotherapy and patient experience. This data is helpful to set expectations for patients and practitioners regarding the process for prosthesis fabrication and follow-up.

This clinical report describes the expeditious treatment of a geriatric patient with squamous cell carcinoma of the nose treated with total rhinectomy, craniofacial implant placement, and a nasal prosthesis.

Postsurgical malocclusion is a possible sequela of care following segmental mandibulectomy and osteocutaneous free flap reconstruction. Patient-specific factors may make surgical correction an impossibility. In addition, conservative occlusal adjustments may be insufficient for correction of the occlusion. An alternative approach for the management of severe postoperative malocclusion is to fabricate a maxillary occlusal splint, which establishes interocclusal articulating surfaces and facilitates mastication. The purpose of this report is to demonstrate the technique and utility of a maxillary prosthesis to correct posttreatment malocclusion in the oncologic patient.

Background Radiotherapy (RT), the main treatment for patients with head and neck cancer, can lead to dental complications. Methods We identified 244 patients with squamous cell carcinoma of the tonsil treated with RT from 2004 to 2013. For each patient, we contoured the 10 tooth-bearing regions and calculated the radiation dose (gray, Gy) to each region. From this data set, we built two predictive models to determine the expected maximum radiation dose, one for the non-molar regions and another for the molar regions. Results For the non-molars, the final model included location, T-classification, and overall stage, with a median absolute prediction error of 7.0 Gy. For the molars, the final model included location, T-classification, overall stage, and treatment year, with a median absolute error of 6.0 Gy. Conclusions Our current model offers a good estimation of the maximum radiation dose delivered to different regions of the jaw; future work will independently validate these models.

For patients with head and neck cancer requiring a maxillectomy, obturator prostheses help with quality of life. These patients routinely require adjuvant oncologic treatments with significant adverse effects. Treatment sequelae can leave patients with difficulty speaking and swallowing, reduced salivary function, reduction in maximal incisal opening, and at risk of osteoradionecrosis. A 55-year-old African-American woman presented with significant trismus and reduction in maximal incisal opening after treatment for squamous cell carcinoma of the left maxillary sinus. She had received a left total maxillectomy with adjuvant chemotherapy and radiation treatments. With her reduced opening, she was no longer able to insert her interim obturator prosthesis, which caused difficulty speaking and nasal regurgitation. A cone beam computer tomography (CBCT) scan was made of the patient's maxillectomy defect. From the Digital Imaging and Communications in Medicine (DICOM) file, a definitive cast was 3-dimensionally (3D) printed to fabricate a flexible silicone obturator prosthesis. This treatment has allowed the patient return to a functional quality of life and could help other patients in similar situations.

Background Although metastatic involvement of bony sites including cranial bones is common in neuroblastoma (NB), mandibular metastases (MM) are uncommon, and specific outcomes have not been reported upon in the modern therapeutic era. Methods In this retrospective study, medical records on patients with MM from NB were reviewed. Statistical analysis was performed using the Kaplan-Meier method. Results Of 29 patients, nine (31%) had MM at diagnosis, whereas in 20 (69%) MM were first detected at NB relapse at a median time of 26 (6-89) months from diagnosis. Median maximal diameter of lesions was 3 (range 0.8-4.9) cm. MM were unilateral in 83% of patients, with ascending ramus (55%) and mandibular body (38%) being the two most common sites. All patients received systemic chemotherapy, and 26 (93%) patients received radiotherapy to MM. At a median follow-up of 37.3 (24.2-219.5) months, eight of nine patients with MM at diagnosis did not experience mandibular progressive disease. Eighteen of 20 patients with MM at relapse received therapeutic radiotherapy; objective responses were noted in 78%. Seventy-two percent (5/18) had not experienced relapse within the radiation field at a median of 12 (2-276) months postradiotherapy. Dental findings at follow-up after completion of NB therapy included hypodontia, hypocalcification of enamel, and trismus. Median 3-year overall survival in patients with relapsed MM was 51 ± 12% months from relapse. Conclusion MM when detected at diagnosis is associated with a prognosis similar to that for other skeletal metastases of NB. Radiotherapy is effective for control of MM detected both at diagnosis and relapse. Significant dental abnormalities posttherapy warrant regular dental evaluations and appropriate intervention.

Objectives/hypothesis The current role of maxillofacial prosthetic care for head and neck cancer patients is not well understood. Additionally, perceived barriers for service provision are unknown. The purpose of this study was to evaluate the current role of maxillofacial prosthetic care at National Cancer Institute (NCI)-designated comprehensive cancer centers and to identify perceived barriers to care. Study design Multicenter, cross-sectional survey of head and neck division leaders at NCI-designated comprehensive cancer centers. Methods Each head and neck division leader from the 47 NCI-designated comprehensive cancer centers was invited to participate. The main outcomes of this study were: 1) to evaluate the current role of maxillofacial prosthetics for the surgically treated head and neck cancer patient within NCI-designated comprehensive cancer centers and 2) to identify perceived barriers to care. Measured outcomes were obtained from an anonymous online survey and reported. Results Twenty-eight of the 47 head and neck service chiefs responded (60% response rate). Respondents expressed preference for prosthetic rehabilitation for hard palate/upper gum, auricular, and nasal defects. Local flap or free tissue transfer was preferred for lower gum and soft palate defects. Cost-related factors were among the most reported perceived barriers to maxillofacial prosthetic care. Conclusions Maxillofacial prosthetics have an important role in the rehabilitation of the head and neck cancer patient. Perceived barriers for services exist, particularly as it relates to cost. Providers should be aware that these issues are likely to be more severe in regional or community centers. Level of evidence NA Laryngoscope, 129:409-414, 2019.

Rehabilitation of oral functions following surgery on the jaws is a goal that is often difficult to achieve. Removable dentures supported by remaining teeth or gum are often unstable and seldom satisfactory. On the other hand, endosseous (dental) implants offer a mechanism to provide stability to the dentures. This review, discusses factors related to the tumor, patient, treatment, and physicians which impact upon the feasibility and success of dental implants in patients with oral cancer.

Management of patients undergoing treatment for cancer requires a multidisciplinary team including general dentistry providers; however, the relative knowledge and training of general dentists in the management of this patient population are relatively unknown. The purpose of this study was to assess the oncology curricula of postgraduate general dentistry training programs, from the perspective of the program directors, to better understand the opportunities for and/or barriers to dental care for cancer patients. A cross-sectional survey was sent to the 275 Commission on Dental Accreditation-accredited programs; 82 program directors responded (response rate, 30%). More than 50% of respondents indicated "none" or "little" curricular emphasis on cancer biology, bone marrow transplantation, immunotherapy, or prosthetics for use during head and/or neck surgery. Conversely, more than 50% of respondents indicated "moderate" or "substantial" emphasis on acute oral effects of cancer-related therapy, long-term oral effects of cancer-related therapy, antiresorptive medication pharmacology, radiotherapy techniques and biological effects, and osteonecrosis of the jaw. Residents had the most experience with radiotherapy patients and the least with bone marrow or transplantation patients. Overall, general dentistry program directors were enthusiastic to participate in the multidisciplinary team but reported challenges to including oncology curricula in residency training programs. Training for general dentistry providers in formalized postgraduate residency programs may be variable or limited-as a result, communication regarding patient management is critical. Opportunities exist to enhance the general dentistry curricula and, thereby, improve access to dental care for patients receiving treatment for cancer.

CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available. However, most studies reported so far include small series with limited follow-up information, which preclude a more definitive assessment. The present work investigates the clinicopathologic features of a large cohort of sarcomas with CIC gene rearrangement, to define their clinical presentation, morphologic spectrum, and outcome. Our study further examines the overall survival of the CIC-positive cohort compared with a control group of EWSR1-rearranged Ewing sarcoma matched for age and stage. The study cohort included 115 patients, with a mean age of 32 years and a slight male predominance. Most tumors occurred in the soft tissue (86%), predominantly deep-seated and equally divided among trunk and extremity, followed by visceral locations (12%) and rarely in the bone (3%). Microscopically, most tumors showed round to ovoid cytomorphology but half of the cases showed also focal areas of spindling and epithelioid/rhabdoid phenotype, with frequent myxoid stromal changes. Variable CD99 reactivity was seen in 84% cases, with a diffuse pattern only in 23% of cases, whereas nuclear WT1 was seen in 92%. A CIC-DUX4 fusion was detected in 57% of cases, with either DUX4 on 4q35 (35%) or on 10q26 in 25 (22%) cases. No FOXO4 gene rearrangements were present in 39 cases tested. Clinical follow-up was available in 57 patients, with a 5-year survival of 43%, which was significantly lower than the 77% 5-year survival in the control Ewing sarcoma group (P=0.002). Our findings show that CIC-DUX4 sarcomas occur most commonly in young adults within the somatic soft tissues, having a wide spectrum of morphology including round, epithelioid and spindle cells, and associated with an aggressive clinical course, with an inferior overall survival compared with Ewing sarcoma. The results support the classification of CIC-rearranged tumors as an independent molecular and clinical subset of small blue round cell tumors distinct from Ewing sarcoma.

Modern radiotherapy delivery systems and treatment strategies are aimed at limiting the irradiation of healthy structures in the head and neck. This seeks to mitigate post-treatment toxicities and complications such as osteoradionecrosis of the jaw. Given the changes to radiotherapy, conventional workflows for the management of patients requiring dentoalveolar surgery may no longer be suitable. It may therefore be appropriate to revisit current treatment algorithms for the management of patients with radiotherapy to the jaws who require dentoalveolar surgery. At present, there are poor data on this. Development of a randomised trial may be warranted to establish the true relative risk for extraction of teeth in the setting of modern radiation therapy delivery systems.

PURPOSE To report the feasibility of oral rehabilitation in patients who had undergone marginal mandibulectomy and to describe the factors that impact the selection of a mandibular resection prosthesis. MATERIALS AND METHODS A retrospective review of patients who had undergone marginal mandibulectomy over a 14-year period at a tertiary care cancer center was undertaken. Measurements of the vertical height and width of the mandible and the distance between the alveolar crest and mandibular canal were measured after marginal mandibulectomy. The feasibility and success of tooth-borne or implant-supported resection prostheses were measured. RESULTS Following marginal mandibulectomy, the median heights between the alveolar crest and lower border of the mandible were 21.8 mm, 17.7 mm, and 14.3 mm in the anterior, premolar, and molar regions, respectively. However, the median distances between the alveolar crest and the mandibular canal in the premolar and molar regions were only 3.98 and 3.4 mm, respectively. These residual bone measurements are not satisfactory for implant-supported mandibular resection prostheses, which can be considered only in the anterior region of the mandible. Patients with marginal mandibulectomy in the premolar and molar regions can only be rehabilitated with removable dentures, provided they have remaining stable teeth to clasp and anchor the removable denture. CONCLUSION Implant-supported resection prostheses after marginal mandibulectomy are feasible only in the anterior segment of the mandible and are not possible in the premolar and molar regions.

Leiomyosarcoma is a rare malignant condition occurring in the maxillofacial region in which the mandible may be affected. Management of this tumor in the mandible may include segmental mandibulectomy, osteocutaneous fibula free-flap reconstruction, endosseous implants, and postoperative radiotherapy. Posttreatment malocclusion can be managed with an overpartial mandibular resection prosthesis. The purpose of this report is to describe the expeditious oral rehabilitation of an oncologic patient with posttreatment malocclusion, demonstrating the utility of an overpartial mandibular resection prosthesis.

Objective The purpose of this study was to compare the dosimetric distribution of ipsilateral proton beam radiation therapy (PBRT) with intensity-modulated radiation therapy (IMRT) in the tooth-bearing region of the mandible in patients with head and neck cancer (HNC). Study Design The mandibular dosimetric distribution in patients with head and neck cancer treated with ≥60 Gy relative biologic equivalent PBRT was evaluated. The mean radiation doses were calculated in 5 regions: ipsilateral molar, ipsilateral premolar, anterior, contralateral premolar, and contralateral molar (CM) regions. CM was used as the reference region for comparative analysis. The mandibular dosimetric distribution in patients treated with PBRT was compared with that in IMRT patients with similar tumor sites and planning target volumes. Results The mean radiation dose to the contralateral regions was lower in patients treated with PBRT compared with those treated with IMRT. The average mean radiation doses to the reference region (CM) in patients treated with PBRT (relative biologic equivalent) versus IMRT were oropharynx (2.2 Gy vs 23.2 Gy; P P = .01), and oral cavity (0.4 Gy vs 15.6 Gy; P = .006). Conclusions This study revealed the effective tissue-sparing capability of PBRT compared with IMRT. Utilization of PBRT could translate to less radiation-related toxicity.

Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort.Patients managed for HNRMS in our institution (1996-2015) were analyzed. The presence of a FOXO1 fusion was required for the classification of ARMS. MYOD1 mutations in SRMS-ScRMS were tested when material available. Univariate and multivariate analyses were performed to evaluate variables related to overall survival (OS).Ninety-nine HNRMS patients (52 males and 47 females, mean of 16years) were included in the study after pathologic re-review. The most common location was parameningeal (PM) (n=64), followed by non-orbital/non-PM (n=25) and orbital (n=10). There were 53 ERMS, 33 fusion-positive ARMS and 13 SRMS-ScRMS [SRMS (8); ScRMS (5)]. The 5-year OS rate for ERMS patients was significantly higher (82%) compared to ARMS (53%) and SRMS-ScRMS (50%) [SRMS (75%); ScRMS (30%)]. Univariate analysis showed that survival was dependent on histology (P=0.012), tumor size5cm (P0.001), regional lymph node involvement (P=0.002), metastasis at initial presentation (P0.001), stage (P0.001), and recurrence (P=0.002). Multivariate analysis confirmed histologic subtype to be significant (P=0.043).Our findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS having an equally unfavorable outcome.

PurposeMetastatic solid tumors to the oral cavity are rare, frequently indicative of an end-stage disease process, and associated with poor survival rates. We performed a 20-year retrospective clinical analysis of our institution's cases of solid metastases to the oral cavity, and investigated these patients' clinical outcomes.Material and methodsA retrospective study of patients with metastatic solid tumors to the oral cavity over a 20-year period (October 1996 to September 2015) was conducted at Memorial Sloan Kettering Cancer Center. Patients were selected if they had a histopathologically confirmed diagnosis. Demographic, pathologic, and clinical information were reviewed to identify patient outcomes.ResultsA total of 44 patients with metastatic non-melanocytic non-hematopoietic tumor to the oral cavity were identified: 24 males and 20 females (39 adults and 5 children) with a mean age of 54.3 years. In all, 24 cases involved the jaw and 20 cases involved the oral soft tissue. Eight patients (18.2%) had oral cavity metastases as the first indication of an occult malignancy. In adult patients, the common primary sites were the lungs (n=9, 20%), kidney (n=7, 16%), breast (n=5, 11%), and colon (n=4, 9%); and in pediatric patients the adrenal gland (3/5) was the most common site. Of the adult patients, 33 (84.6%) died of disease. From the time of metastasis diagnosis, patients with jaw metastases had a median and mean survival of 12 months and 27.7 months, respectively. In comparison, patients with oral soft tissue metastases had a median survival time of 5 months, and mean of 8 months. One pediatric patient (20%) died of disease 8 months after metastasis diagnosis.ConclusionMetastatic solid tumors to the oral cavity can be the first sign of a malignancy. Pediatric patients with oral cavity metastases have a better prognosis compared to adult patients. In this series, adults with oral soft tissue involvement had shorter survival times compared to patients with jaw involvement.

Osteoradionecrosis (ORN) remains an unintended debilitating complication of radiation therapy despite the advent of intensity-modulated radiation therapy (IMRT) which aims to deliver doses of radiation to the tumor site while minimizing doses to healthy tissues [[1], [2], [3], [4]. The etiopathogenesis of ORN has been attributed to the avascular effect of radiation to the bone resulting in hypoxia, hypovascularity, and hypocellularity [5], [6]. Radiation-induced fibrosis has also been implicated in the pathophysiology of ORN [7. Recent studies have placed reported incidences of ORN at 1–30% [2], [8], [9], [10], [11]. ORN of the jaw was defined as an area of exposed necrotic bone greater than 1 cm in an area of previous irradiation that failed to heal after 6 months [5]. This definition of ORN has been used for years and still remains the most widely used clinical criterion for the diagnosis of ORN though it fails to incorporate cases with radiologic evidence of necrosis with intact mucosa [5], [12], [13], [14], [15]. Although a report by Van Merkesteyn et al. described a case of ORN of the jaw with intact mucosa [16], subsequently only two series have likewise reported this condition. In 2000, Store and Boysen reported 17 patients with radiographic osteoradionecrosis of the jaw (rORN) with intact mucosa at initial diagnosis as did He et al. in a recent article where they described 16 patients presenting with rORN with intact mucosa [17], [18]Thus, it appears that rORN with intact mucosa is underdiagnosed. The objectives of this article are to: 1. Describe new cases of rORN with intact mucosa. 2. Correlate the dosimetric analyses of the involved area with the radiographic presentation and to determine the best predictor of rORN with intact mucosa. 3. Propose modification of Store and Boysen’s staging system of ORN. 4. Propose clinical guidelines for early identification of rORN with intact mucosa.

Successful intraoral rehabilitation for patients with head and neck cancer can be extremely challenging to both the patient and the physician due to anatomical, functional, and esthetic changes from the cancer and its treatment. The measures with optimal oral hygiene to prevent or minimize the sequelae of cancer treatments are fundamental to preservation of function and avoidance of complications of therapy. In patients with loss of teeth, endosseous (dental) implants offer an option to improve intraoral rehabilitation. This review presents the indications, problems, and relevant issues pertaining to the use of endosseous implants in a head and neck oncologic population. The problems associated with the traditional approaches for cancer treatment including surgery, radiotherapy, and chemotherapy, as well as those with antiresorptive medications are discussed as they relate to consideration for endosseous implants. This information can aid dental practitioners to select appropriate candidates for implant surgery, minimize postoperative complications, and maximize the successful oral rehabilitation of this patient population.

After ablative surgery, especially a total maxillectomy, an obturator is commonly used as a method of reconstruction. However, the loss of a palatal denture-bearing area and vestibular retentive undercuts leaves an anatomically deficient base on which to construct the definitive prosthesis. As a result, retention and stability is compromised. A solution to the retention problem is to construct an obturator that engages undercuts and scar bands. Engagement of all undercuts can lead to a prosthesis that is too cumbersome and difficult to insert, especially in a patient with scars after radiation. In this article, a technique for creating a 2-piece magnetic obturator that engages the nasal scar band is described.

ObjectiveThe aim of this study was to investigate the relationship between type of antiresorptive medication and medication-related osteonecrosis of the jaw (MRONJ) onset and the role of premedication dental evaluation (PMDE) in the prevention of MRONJ.Study designOur database of patients with MRONJ was reviewed. The Kruskal-Wallis test was used to analyze the onset dose of the 3 frequent medication types associated with MRONJ. To evaluate the role of PMDE in the prevention of MRONJ, all patients on antiresorptive and/or antiangiogenic medications seen in the Dental Service of Memorial Sloan Kettering Cancer Center during a 10-year period were subclassified into 2 groups. Group I comprised patients seen for PMDE before the commencement of A/A and group II patients seen after prior exposure to antiresorptive and/or antiangiogenic medications. Fischer's exact test was used to compare the incidence of MRONJ in both groups.ResultsPatients on denosumab developed MRONJ earlier compared with zoledronate and pamidronate (P = .003). Group I had a significantly reduced incidence of MRONJ (0.9%) compared with group II (10.5%) (P

Statement of problem Treatment and timing considerations for patients seeking oral rehabilitation after marginal or segmental mandibulectomy (with osseous reconstruction) are not well understood. Purpose The purpose of this retrospective review study was to report the type and timing of oral rehabilitation for mandibular defects without discontinuity and to describe additional treatment considerations for rehabilitation. Material and methods The records were reviewed of all patients who received a mandibular resection prosthesis after marginal mandibulectomy, marginal mandibulectomy with fasciocutaneous free-flap reconstruction, and segmental mandibulectomy with fibula free-flap reconstruction between 2000 and 2017 in the tertiary cancer care institution. Patients not treated by the Dental Service in the institution were excluded. The specific type of rehabilitation was noted, as was the time interval between primary surgery and prosthesis delivery. Results During the study period, 111 consecutive patients were treated by the Memorial Sloan Kettering Cancer Center Dental Service for mandibular rehabilitation. Forty-three patients underwent marginal mandibulectomy, 9 patients underwent marginal mandibulectomy with fasciocutaneous free-flap reconstruction, and 59 patients underwent segmental mandibulectomy with fibula free-flap reconstruction. Most patients in all 3 groups received mandibular resection prostheses without the use of endosseous implants. Only 4 (8%) patients who had undergone marginal mandibulectomy underwent endosseous implant placement, all of which followed marginal mandibulectomy in anterior mandibular segments without free-flap reconstruction. Patients who underwent marginal mandibulectomy with fasciocutaneous free-flap reconstruction were only restored with removable mandibular resection prostheses, and none had endosseous implants. In patients who underwent segmental mandibulectomy, 13 (22%) were rehabilitated with endosseous implants. The majority in this cohort (>50%) received radiation therapy as part of their treatment. The median time to oral rehabilitation was 8 months after marginal mandibulectomy, 14 months after marginal mandibulectomy with fasciocutaneous free-flap reconstruction, and 12 months after segmental mandibulectomy with fibula free-flap reconstruction. Conclusions Timing for oral rehabilitation may differ depending on the treatment modality followed for mandibular tumors in the patient with oral cancer. However, most patients in this cohort underwent rehabilitation with removable mandibular resection prostheses regardless of the timing of care. Endosseous implants were used infrequently, but research is needed to better understand their potential role and indication in the patient with oral cancer.

IMPORTANCE: The current role of maxillofacial prosthetic care for head and neck cancer patients is not well understood. Additionally, perceived barriers for service provision are unknown. OBJECTIVE: The purpose of this study is to evaluate the current role of maxillofacial prosthetic care at NCI-Designated Comprehensive Cancer Centers and to identify perceived barriers to care. DESIGN: cross-sectional survey SETTING: Multicenter survey of Head and Neck Division leaders at NCI-Designated Comprehensive Cancer Centers PARTICIPANTS: Each Head and Neck Division Leader from the 47 NCI-Designated Comprehensive Cancer Centers was invited to participate. MAIN OUTCOME(S) AND MEASURE(S): The main outcomes of this study are: (1) to evaluate the current role of maxillofacial prosthetics for the surgically treated head and neck cancer patient within NCI-Designated Comprehensive Cancer Centers and (2) to identify perceived barriers to care. Measured outcomes were obtained from an anonymous online survey and reported. RESULTS: 28 of the 47 Head and Neck Service Chiefs responded (60% response rate). Respondents expressed preference for prosthetic rehabilitation for hard palate/upper gum, auricular, and nasal defects. Local flap or free tissue transfer was preferred for lower gum and soft palate defects. Cost related factors were among the most reported perceived barriers to maxillofacial prosthetic care. CONCLUSIONS AND RELEVANCE: Maxillofacial prosthetics have an important role in the rehabilitation of the head and neck cancer patient. Perceived barriers for services exist, particularly as it relates to cost. Providers should be aware that these issues are likely to be more severe in regional or community centers.

The basic objective in prosthetic restoration of confluent maxillary and orbital defects is to achieve a comfortable, cosmetically acceptable prosthesis that restores speech, deglutition, and mastication. It is a challenging task complicated by the size and shape of the defects. The maxillary obturator prosthesis often satisfies the objective of adequate deglutition; however, orbital defects that are not obturated in the medial, septal, or posterior walls allow air to escape, negatively impacting phonation. This article describes a technique to achieve favorable prosthetic rehabilitation in a patient with a maxillectomy and ipsilateral orbital exenteration. The prosthetic components include maxillary obturator, orbital conformer, and orbital prosthesis connected using rigid magnetic attachments.

Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST. MPNSTs with PRC2 loss are associated with complete loss of trimethylation at lysine 27 of histone H3 (H3K27me3), which emerged as a reliable immunohistochemical marker in the diagnosis of sporadic and radiation induced MPNST. As the diagnosis of MPNST in the HN is particularly challenging to distinguish from melanoma and other sarcoma types, we carried out a clinicopathologic analysis on HN-MPNST patients managed at our institution over a 20-year period (1997-2016), using the latest diagnostic criteria including H3K27me3 staining and other molecular investigations. The overall survival of HN-MPNST was compared with other HN soft tissue sarcomas. The diagnosis of HN-MPNST was confirmed in 13 patients (seven males and six females), with a mean age of 31 years; with 3 (23%) patients being of pediatric age. The most common site was the neck soft tissue (77%). Two-thirds of patients (n = 9) had stigmata of NF1, three had prior radiotherapy and only one developed a de novo MPNST. All except one tumor (86%) tested showed loss of H3K27me3 expression, including all non-NF1 patients. The 2 and 5-year DSS rates were 50 and 30%. The 2-year DFS rate was 21%. Adverse predictors on DSS included adult age (p = 0.011), prior-history of RT (p = 0.003) and recurrence (p = 0.003). Compared to other molecularly confirmed subsets of HN sarcomas (Ewing and Ewing-like sarcoma, rhabdomyosarcoma and synovial sarcoma), HN-MPNST had the worst overall survival (p

CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the ‘Ewing sarcoma-like tumors’. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations. A total of 41 HN round cell sarcoma patients were selected from our institutional and consultation files, including 25 ES (median 20 years) and 16 CRS (median 29 years). Clinical follow-up information was available for all ES patients, ranging from 4 to 436 months (median 70 months), while for CRS, follow-up information was available in 11 patients (69%), ranging from 1 to 269 months (median 27 months). The most common location for ES was the facial and jaw bones (56%), while CRS occurred exclusively in the soft tissue, commonly in the neck. CRS showed variable CD99 staining in 75% of cases and diffuse WT1 (6/6) reactivity, while all ES expressed diffuse membranous staining for CD99 but none for WT1 (0/6). The 2-year overall survival (OS) rate for HN-CRS patients was 78%, while for HN-ES it was 100%. The OS of ES and CRS showed a trend toward a favorable outcome for HN-round cell sarcomas compared to other sites. Our findings suggest that HN-CRS have different clinical presentation and pathologic features compared to ES and should be classified as a stand-alone pathologic entity.

Objective To determine the prevalence and correlation of various risk factors [radiation dose, periodontal status, alcohol and smoking] to the development of osteoradionecrosis (ORN). Patients and methods The records of 1023 patients treated with IMRT for oral cavity cancer (OCC) and oropharyngeal cancer (OPC) between 2004 and 2013 were retrospectively reviewed to identify patients who developed ORN. Fisher exact tests were used to analyze patient characteristics between ORN patients with OCC and OPC. Paired Wilcoxon tests were used to compare the dose volumes to the ORN and contralateral non-ORN sites. To evaluate an association between ORN and risk factors, a case-control comparison was performed. One to 2 ORN-free patients were selected to match each ORN patient by gender, tumor site and size. General estimation equations models were used to compare the risk factors in ORN cases and matched controls. Results 44 (4.3%) patients developed ORN during a median follow-up time of 52.5 months. In 82% of patients, ORN occurred spontaneously. Patients with OPC are prone to develop ORN earlier compared to patients with OCC (P = 0.03). OPC patients received a higher Dmax compared to OCC patients (P = 0.01). In the matched case-control analysis the significant risk factors on univariate analysis were poor periodontal status, history of alcohol use and radiation dose (P = 0.03, 0.002 and 0.009, respectively) and on multivariate analysis were alcohol use and radiation dose (P = 0.004 and 0.026, respectively). Conclusion In our study, higher radiation dose, poor periodontal status and alcohol use are significantly related to the risk of developing ORN.

CASE PRESENTATION In October 2012, a 70-year-old black woman presented to her ophthalmologist, who noted that she had a left parotid mass. She was subsequently referred to a hospital to have the mass evaluated. It was unclear how long the mass was present, but there were no symptoms. The patient reported no family history of malignancy, and her health was significant for type 2 diabetes mellitus, non-insulin-dependent. The patient had smoked 2 packs a day for 22 years, but she stated that she had quit 40 years ago. She stated she drank 1 to 2 alcoholic beverages per month. At an outside hospital, ultrasonography found a heterogeneously hypoechoic mass with irregular margins containing focal necrosis with possible deep extracapsular extension measuring 1.96 2.49 cm. No increased flow signal was seen on Doppler mode. A fine-needle aspiration (FNA) of the parotid mass was suspicious for acinic cell carcinoma. Within the same month, the patient was sent to Memorial Sloan Kettering Cancer Center. A computed tomography (CT) scan of the neck found an ill-defined, enhancing soft tissue mass in the left parotid tail with no deep parotid involvement, measuring 2.3 1.9 2.0 cm (Figure 1). No abnormal lymphadenopathy was noted in the neck. A second FNA taken of the left parotid found a salivary gland neoplasm with a cylindromatous pattern, which favored pleomorphic adenoma (Figure 2). The FNA slides from the previous hospital were also reviewed, and ultimately the diagnoses encompassed a differential diagnosis that included both acinic cell carcinoma and pleomorphic adenoma. A positron emission tomographyecomputed tomography scan found a 1.3 1.5-cm left parotid nodule with a maximum standardized uptake value of 2.7 (Figure 3). No hypermetabolic lymphadenopathy was noted in the neck.

Ameloblastoma is a histologically benign but locally aggressive tumor of the jaws. We conducted a retrospective cohort study to review the clinical, radiologic, and pathologic features of patients with ameloblastoma of the mandible and maxilla and to report the outcomes of treatment. Our study population was made up of a series of 30 consecutively presenting patients-15 men and 15 women, aged 19 to 81 years (median: 61.5)-who had undergone their primary treatment of ameloblastoma of the mandible or maxilla at Memorial Sloan Kettering Cancer Center from January 1987 through December 2012. In addition to demographic data, we compiled information on clinical characteristics, imaging findings, the type of surgery, surgical margins, adjuvant treatments, histologic patterns, length of follow-up, time to recurrence, treatment of recurrence, and factors that had an influence on recurrence. All but 2 patients with negative margins were cured. Favorable outcomes were associated with the administration of adjuvant postoperative radiotherapy for patients with positive margins and a repeat resection for patients with recurrences. Complete excision with negative margins, however, remains the gold standard for curative treatment.

Aim: The aim of this study is to retrospectively, observe a consecutive series of patients with segmental mandibulectomy defects reconstructed with fasciocutaneous free flaps and mandibular resection prostheses, and to review treatment concepts for the management of such patients. Settings and Design: Observational study done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Materials and Methods: Records were reviewed of all patients who had fasciocutaneous free-flap reconstruction and fabrication of mandibular resection prostheses following segmental mandibulectomy between 2000 and 2017 at a tertiary cancer center. Mandibular resection prosthesis fabrication interval data, as well as follow-up interval data, were recorded. Statistical Analysis Used: Descriptive statistics. Results: Twenty-one consecutive patients had mandibular resection prostheses fabricated following segmental mandibulectomy and fasciocutaneous free-flap reconstruction during the study. The median time for mandibular resection prosthesis delivery following surgery was 9 months (range 4–41 months). There was a median of two-follow-up visits (range 0–4) within the first 90 days of mandibular resection prosthesis delivery. Conclusions: Oral rehabilitation with mandibular resection prosthesis following segmental mandibulectomy and fasciocutaneous free-flap reconstruction is an attainable treatment goal for the oncologic patient. Reviewing the proposed course of care is helpful for patient management.

Purpose Oversuppression of bone turnover can be a critical factor in the pathogenesis of osteonecrosis of the jaw (ONJ). We investigated N-telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) as potential predictors of ONJ onset. Patients and Methods Patients with ONJ and available stored serum were identified retrospectively from the institutional databases. Four approximate points were examined: point of ONJ diagnosis and 12, 6, and 1 month before the diagnosis. NTX and BAP were measured using enzyme-linked immunosorbent assays and examined as possible predictors of ONJ. Results From March 1998 to September 2009, we identified 122 patients with ONJ. Of these, 56 (46%) had one or more serum samples available. Overall, 55 patients (98%) received bisphosphonates. Using the exact dates, no obvious patterns in either NTX or BAP were noted. Similarly, using the ordinal points, no evidence of suppression of NTX or BAP over time was seen. The consecutive median values were as follows: The median NTX values were 8.0 nmol/L (range 3.8 to 32.9) at 12 months before ONJ; 9.5 nmol/L (range 4.7 to 42.7) at 6 months; 9.5 nmol/L (range 4.5 to 24.6) at 1 month, and 10.4 nmol/L (range 4.4 to 32.5) at the ONJ diagnosis. The median BAP values were BAP 18.0 U/L (range 7.0 to 74) at 12 months before ONJ; 18.0 U/L (range 4.0 to 134) at 6 months; 14.0 U/L (range 4.0 to 132) at 1 month, and 18.0 U/L (range 0.7 to 375) at the ONJ diagnosis. Only 2 patients (4%) had NTX and 17 (30%) had BAP below the normal range at the ONJ diagnosis. Conclusions In the present large retrospective study, no trends were seen in the NTX and BAP levels before the ONJ diagnosis.

Background and purpose To study internal and external generalizability of temporal dose–response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Material and methods Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006–2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1 , and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p -values, and Hosmer–Lemeshow p -values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose–response curves. Results The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11–12months) in Cohort1/Cohort2 . Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi ( Cohort1 : 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p =0.0002±0.002; p HL =0.22±0.23; Cohort2 : AUC=0.81; p HL =0.27). The identified minimum Dmean contra thresholds were lower than in the QUANTEC guidelines ( Cohort1/Cohort2: Dmean contra =12/19Gy; Dmean contra , Dmean ipsi =16, 25/20, 26Gy). Conclusions Increased Dmean contra and Dmean ipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose–response relationship was established for this follow-up time.

ObjectiveTo determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma.Patients and methodsWe retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS). Fisher exact test was performed to evaluate variables related to local recurrence.ResultsThirty-four patients (20 males and 14 females, mean of 31years) with SS18-SSX fusion-positive SS-HN were identified. The parapharyngeal region of the neck was the most common site. The mean tumor size was 4.8cm (0.8-10cm). Two-thirds (n=23) of cases had a monophasic histology. The 2, 5 and 10-year DSS rates were 97%, 79% and 68%. The 5-year DSS rates for the adult/pediatric cohort were 74%/88%. Recurrence showed significant effect on DSS (p=0.021). There was no significant effect on DSS with age, therapy modality, tumor site, surgical margin, tumor size (⩽5cm vs. >5cm) and histopathologic subtype. Tumor site (i.e. skull base/paranasal sinus region) was associated with local recurrence (p=0.003).ConclusionIn our cohort DSS rate was associated with recurrence. Tumors located in the skull base/paranasal sinus region were associated with a higher rate of local recurrence. Thus appropriate selection of high risk patients who can benefit from multimodality therapies might improve survival.

Dentofacial developmental abnormalities have been reported in head and neck rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy technique and chemotherapy. This current study investigates dentofacial long-term effects among HNRMS survivors managed with intensity-modulated radiotherapy (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal radiotherapy technique, which delivers high doses of radiation to the tumor target while minimizing doses received by the surrounding normal tissues. The medical records and radiographs were reviewed to identify the following: 1. Facial asymmetry and jaw hypoplasia. 2. Effects on the dental tissue causing tooth agenesis/hypodontia, root agenesis/stunting/malformation, and/or enamel hypoplasia. 3. Trismus, hyposalivation/xerostomia. Thirteen patients reviewed were evaluated at the dental service. Seven patients presented with facial asymmetry and jaw hypoplasia, 9 patients presented with effects on the dental tissue [root agenesis/stunting/malformation (9), tooth agenesis/hypodontia (7) and enamel hypoplasia (3)] and 7 patients developed trismus and /or xerostomia. All patients with facial asymmetry and jaw hypoplasia also developed dental abnormalities. Patients with dentofacial developmental abnormalities were ≤ 7 years of age at treatment. Our study shows that dentofacial developmental abnormalities are still a burden in the era of IMRT and as prognosis of childhood malignancy improves and more patients become long-term survivors, these late dentofacial sequelae among childhood cancer survivors will be common. To minimize these complications, dental oncologists should be integrated into the care of children with head and neck cancers.

PurposeThe aim of this study was to estimate the prevalence of trismus in oral and oropharyngeal cancer patients (OOPC) treated with intensity-modulated radiation therapy (IMRT) and to identify the role of risk factors in patients who developed trismus.Materials and methodsA retrospective cohort study of OOPC treated with IMRT in our institution from 2009 to 2014 was performed. Patients eligible for this study had pre-RT and post-RT maximal inter-incisal opening (MIO) measurements at 6-48 months post-RT, treated with high-dose radiation (≥60Gy) and pre-RT MIO ≥36mm. A descriptive analysis to identify the incidence of trismus, with trismus stated as MIO ≤35mm at or after 6 months post-RT measurement was performed. The role of risk factors such as age, gender, tumor site, tumor size (T), tumor stage, pre-RT MIO measurements and radiation dose to the tumor were assessed using Fisher exact test and the radiation doses to the ipsilateral muscles of mastication in patients who developed trismus were assessed by matching with control (non-trismus) patients using Wilcoxon Signed Rank test.ResultsThe study consisted of 54 patients with a median age of 55 years and 81% were males. The median follow-up time was 10 months. The prevalence of trismus was 14.8%. Patients with pre-RT MIO measurements ≤40mm were at risk of developing trismus (P&nbsp

BackgroundThe aims of this study were to investigate temporal patterns and potential risk factors for severe hyposalivation (xerostomia) after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and to test the two QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines.Patients and methodsSixty-three patients treated at the Memorial Sloan Kettering Cancer Center between 2006 and 2015, who had a minimum of three stimulated whole mouth saliva flow measurements (WMSFM) at a median follow-up time of 11 (range: 3-24) months were included. Xerostomia was defined as WMSFM ≤25% compared to relative pre-radiotherapy. Patients were stratified into three follow-up groups: 1