Radiotherapy For Squamous Cell Carcinoma Research Articles

Neighborhood Deprivation and Symptoms, Psychological Distress, and Quality of Life Among Head and Neck Cancer Survivors

Socioeconomic deprivation is associated with increased risk of poor health and quality-of-life (QOL) outcomes in head and neck cancer (HNC) survivors. However, there are few data on how neighborhood deprivation affects patient-reported outcome measures (PROMs) in HNC survivors. To investigate whether neighborhood socioeconomic deprivation is associated with symptom burden, psychological distress, and QOL among HNC survivors. This cross-sectional study used prospectively collected data from patients seen in a university-affiliated multidisciplinary HNC survivorship clinic between September 2018 and September 2021 who received radiotherapy for squamous cell carcinoma of the oral cavity, oropharynx, and larynx or hypopharynx. Neighborhood socioeconomic deprivation, measured using the Area Deprivation Index (ADI). The PROMs pertaining to symptom burden and severity of psychological distress were measured using the Neck Disability Index, Insomnia Severity Index, the 10-item Eating Assessment Tool, the Generalized Anxiety Disorder 7-item scale, and the 8-item Patient Health Questionnaire. Physical and social-emotional QOL were obtained using the University of Washington QOL questionnaire. Multivariable linear regression analysis adjusting for individual-level sociodemographic, comorbidity, and treatment characteristics investigated the association between ADI and PROMs. A subgroup analysis was performed to compare the lowest (most affluent areas: ADI, 0%-20%) and highest (most deprived areas: ADI, 80%-100%) ADI quintiles. A total of 277 patients were included in the final analysis (mean [SD] age, 64.18 [9.60] years; 215 [77.6%] male). Cancer sites were the oral cavity (52 [18.8%]), oropharyngeal area (171 [61.7%]), and larynx or hypopharynx (54 [19.5%]). Multivariable analysis showed that for every 1-point increase in ADI, social-emotional QOL changed by -0.14 points (95% CI, -0.24 to -0.05 points), anxiety increased by 0.03 points (95% CI, 0.01-0.06 points), and neck disability worsened by 0.05 points (95% CI, 0.01-0.10 points). Compared with patients in the most affluent areas, those in the most deprived areas had significantly lower physical (-15.89 points; 95% CI, -25.96 to -2.31 points; Cohen d = -0.83) and social-emotional (-13.57 points; 95% CI, -22.79 to -3.49 points; Cohen d = -0.69) QOL and higher depression (2.60 points; 95% CI, 0.21-4.40 points; Cohen d = 0.52), anxiety (3.12 points; 95% CI, 1.56-4.66 points; Cohen d = 0.61), insomnia (3.55 points; 95% CI, 0.33-6.41 points; Cohen d = 0.54), and neck disability (5.65 points; 95% CI, 1.66-9.55 points; Cohen d = 0.66) scores. In this cross-sectional study, a higher ADI score was associated with higher risk of increased psychological distress, higher symptom burden, and decreased QOL after treatment among HNC survivors. These findings suggest that proactive, patient-centered interventions are needed to address these disparities.

Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity

Acute Oral Mucositis During Hypo-Fractionated Radiation in Squamous Cell Carcinoma of Oral Cavity

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. NA Laryngoscope, 134:2019-2027, 2024.

Long-term follow-up of osteoradionecrosis of the mandible

Aim Investigating the prevalence of mandibular ORN in a single Swedish Oncology Center. Methods A total of 450 patients, treated with radiotherapy for squamous cell carcinoma in the oropharynx between 2004 and 2014 were included. Three different techniques of radiotherapy were studied. ORN diagnosis was set when clinical signs according to Marx were observed, or if radiological signs were staged according to Schwartz and Kagan. Results Using the staging system, 90 patients (20%) were diagnosed with ORN. The mean age of the ORN patients was 56.6 years, the older the patient the lower the risk of developing ORN (p = .01). The risk of developing ORN for patients receiving Intensity Modulated Radiotherapy was lower compared to patients treated with the other techniques in the multivariable analysis. Brachytherapy significantly increases the risk of ORN. The risk of ORN increased by 8% each year after radiation (p = .04). The mean time to the ORN diagnosis was 3.9 years. In the multivariate analysis, the risk of ORN increased by 13% each year after radiation (p = .0013). Conclusion The mean radiation dose was of greater importance for the risk of ORN than the maximum dose. Elderly people with oropharyngeal cancer were less prone to develop ORN.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p=0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Erratum to “The Results of Radiotherapy for Squamous Cell Carcinomas of the Skin”

Erratum to “The Results of Radiotherapy for Squamous Cell Carcinomas of the Skin”

Dosimetric comparison of 3DCRT and IMRT in radical chemoradiotherapy of squamous cell carcinoma esophagus.

Radical chemoradiation is the standard of treatment for locally advanced squamous cell carcinoma of esophagus and for patients with operable disease, but who are medically unfit or unwilling for surgery. As the esophagus is a central organ, the planning target volume (PTV) is central, lies close to the spinal cord and heart, and is surrounded by the lung, which is a radiosensitive organ. Irradiation of these critical structures is reduced by the use of three-dimensional conformal radiation therapy (3DCRT). Intensity-modulated radiation therapy (IMRT) has the potential to improve the uniformity of dose distribution to the tumor and reduce the dose received by surrounding normal tissues. 1. To compare the dose distribution, conformity, and homogeneity indices in radical radiotherapy of squamous cell carcinoma of esophagus using 3DCRT and IMRT techniques 2. To compare the doses received by critical structures such as heart, lung, spinal cord, and liver. All cases of squamous cell carcinoma esophagus treated with radical chemoradiation to a dose of 50 Gy in 25 fractions using 3DCRT technique from January 2018 to July 2019 were included. IMRT plans were generated for these cases.The parameters that represent dose distribution to the target volume and the dose received by the organs at risk were obtained from the dose-volume histogram. The difference in the mean values of the parameters between the two techniques was calculated. The statistical significance of the difference was determined using Student's t-test and Wilcoxon signed-rank test. The volume of PTV receiving 105% and 107% of prescribed dose was significantly lower with IMRT (3.540% and 0.008%, respectively) compared to 3DCRT (7.654% and 0.623%). The homogeneity index was better with IMRT (0.088 vs. 0.107) than 3DCRT. Conformity index was found to be better with IMRT (1.149 vs. 1.573). Mean heart dose (18.216 vs. 24.591 Gy) and the volume of heart receiving 30 Gy were reduced with IMRT. The volume of lung receiving 20 Gy and the volume receiving 5 Gy were not significantly different between 3DCRT and IMRT. Maximum dose to spinal cord was similar with 3DCRT and IMRT. IMRT avoids areas of excessive irradiation within the PTV. IMRT improves dose conformity to the target volume and homogeneity of dose distribution within the PTV. The cardiac dose is significantly reduced with IMRT. The mean lung dose remains similar to 3DCRT. There is no significant increase in the volume of lung receiving low-dose radiation with IMRT.

OGBN O05 Safety and efficacy of endoscopic self-expanding stent insertion for benign oesophageal strictures – retrospective review of a single-centre case series

Abstract Background Benign oesophageal strictures (BOS) are common and are most often managed with endoscopic balloon or bougie dilation. While self-expanding stents (SES) are a key tool for managing malignant strictures, their role in management of BOS is less well defined, usually being reserved for refractory strictures. Potential benefits include reduced frequency of intervention to stabilise nutritional status, and risks include migration, perforation or erosion. We conducted a single-centre retrospective review of our experience using SES for BOS to evaluate their safety and efficacy. Methods All patients undergoing SES insertion at a tertiary oesophago-gastric surgery unit between November 2015 and November 2020 were retrospectively identified using cross-referencing across 3 internal software systems. Patients undergoing primary SES insertion for BOS were identified, records were retrieved and reviewed. Data was collected on pre-insertion stricture management, post-procedure complications and outcomes including further interventions within the next year. Results During the study period, 425 oesophageal SES were inserted. From these cases, 18 patients underwent primary SES insertion for BOS. 14/18 (78%) of patients were male with a mean age of 68 years. Causes of BOS were reflux (7, 39%), 360 degree radiofrequency ablation of dysplastic Barrett's oesophagus (7, 39%), radiotherapy for squamous cell carcinoma (2, 11%), post-achalasia treatment stricture (1, 6%) and anastomotic stricture (1, 6%). In the 12 months prior to SES insertion, patients underwent a median of 3 (IQR 2–4) balloon dilations. During the immediate preceding month, patients underwent a median of 1 (IQR 0–1) dilations. There were no cases of perforation, bleeding or erosion associated with SES insertion. 5 of 18 (28%) stents migrated. Median interval to the next endoscopy was just over 5 weeks (36 days (IQR 27.25–48). During the following 12 months after stent insertion, patients underwent a median of 5 (IQR 3–9.5) further endoscopies after primary stent insertion. Conclusions Stent insertion for BOS is safe and can provide a period of several weeks before further intervention is required. This may facilitate a period during which oral nutrition can be improved. However, SES for BOS is associated with a significant rate of migration, and patients continue to require frequent interventions after stent insertion. We suggest that SES insertion in this setting should be reserved for selected cases where intensive early dilation has failed to achieve progression in diameter with improvement in symptoms and nutrition as part of a standardised approach to improve management of BOS.

RF35 | PSAT304 A Case of COVID-19 Infection; COVID-19 mRNA-Based Vaccine Induced Human Anti-Mouse Antibodies (HAMA) Interfering With TSH Testing

Abstract A 71-year-old male presented to the endocrine clinic for evaluation of hypothyroidism which has recently been difficult for his primary care physician to control. He initially developed hypothyroidism in 1990 after neck radiation for squamous cell carcinoma of his sternocleidomastoid muscle. He was previously controlled for many years on levothyroxine 150mcg daily with TSH readings in the normal reference range. Patient was infected with COVID-19 in 2020 and was hospitalized for 10 days. He was treated with 5 days of Remdesivir and 10 days of Decadron. 6 months after the infection he received mRNA COVID-19 vaccination. Upon his first visit to the endocrine clinic post COVID-19 infection and vaccination, his TSH was elevated at 90 uIU/mL with a free thyroxine that was elevated at 1.8 ng/dL even after multiple attempts by his primary care physician to increase his Levothyroxine which was up to 225 mcg daily before he was referred to endocrinology. He is compliant with his levothyroxine and takes it on an empty stomach first thing in the morning without any of his other medications. He is not taking iron supplements, biotin or any other supplements or new medications. TSH values had been normal 1 month prior to his COVID-19 infection and was first noted to be abnormal 8 months after his COVID-19 infection and 2 months after his mRNA COVID-19 vaccine. There was no TSH drawn between when he had COVID-19 and when he received his vaccine. It was suspected that he may have a factitious elevation in his TSH due to antibody interference. Labs were drawn for a TSH with human anti-mouse antibodies (HAMA) treatment which resulted with a markedly suppressed TSH at 0.007 uIU/mL with an elevated free thyroxine of 1.94 ng/dL. HAMA antibodies came back elevated at 552 ng/mL. Reference Klee, G., 2000. Human Anti-Mouse Antibodies. Archives of Pathology & Laboratory Medicine, 124(6), pp.921-923. Koshida, S., Asanuma, K., Kuribayashi, K., Goto, M., Tsuji, N., Kobayashi, D., Tanaka, M. and Watanabe, N., 2010. Prevalence of human anti-mouse antibodies (HAMAs) in routine examinations. Clinica Chimica Acta, 411(5-6), pp.391-394. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

Impact of Mandated Online Prescription Drug Monitoring Programs on Opiate Analgesic Use and Patient-Reported Pain during Radiotherapy for Oropharyngeal Cancer

<h3>Purpose/Objective(s)</h3> Owing to the dramatic rise in opiate-related deaths, the use of online prescription drug monitoring programs (PDMPs) concurrent with new laws restricting opiate administration has become commonplace across the U.S. Some oncologists, however, have expressed concerns that they may unintentionally limit treatment access to at-risk oncology populations. As opiates are frequently used in the acute management strategies for those undergoing radiotherapy for squamous cell carcinoma of the oropharynx, we sought to evaluate changes in short-term opiate prescription use following the implementation of mandated use of an online PDMP in an outpatient radiation oncology practice. <h3>Materials/Methods</h3> Between July of 2017 and December of 2019, 64 patients with biopsy-confirmed oropharyngeal squamous cell carcinoma undergoing curative-intent radiotherapy were evaluated and divided into two cohorts: (1) 26 patients treated 1 year before and (2) 38 patients treated 1.5 years following mandated PDMP use and implementation of new opiate prescription laws. The primary endpoint was opiate prescriptions during therapy and within 3 months after therapy as well as patient-reported pain per the Defense and Veterans Pain Rating Scale. Opiate doses were treated as the response in a series of chi-square tests using a three-level format: no vs. 40 to 3000 vs. 3000+ MME. Cochran-Mantel-Haenszel chi-square analysis with the row mean score test statistic assessed any proportional shifts in dose rates between strata of selected prognostic factors. <h3>Results</h3> The median total opiate doses were 975 MME and 1025 MME in the pre- and postintervention groups with no significant differences in MMEs prescribed (p=0.8441). There was also no difference in patient-reported uncontrolled pain (p=0.38) between the treatment cohorts. Univariate analysis showed tonsillar/soft-palate subsite (p<0.01) and alcohol use (p=0.04) were associated with higher rates of prescribed opioids. While 75% of patients (n=48) received opiates during their acute care, 78% (n=50) were off all prescription narcotics by 3 months or sooner following treatment. <h3>Conclusion</h3> Although potential concerns that mandated PDMP use would affect opiate utilization, there was no associated change in total opiate use by MME for the management of acute pain during radiotherapy for patients with oropharyngeal squamous cell carcinoma nor differences in patient-reported uncontrolled pain. Furthermore, despite high utilization of opiates during radiotherapy, few patients continued use past 3 months after treatment.

The imaging of the hypoxic microenvironment in tumorous tissue using PET/CT and PET/MRI

Tissue hypoxia becomes the driver of the micro-environmental transformation of the malignant tumorous tissue in majority of solid tumors. Even more, during the development of solid tumors, a large amount of nutrients is consumed due to rapid proliferation of tumor cells. The way of use of nutrients could be assessed using the probes during positron emission tomography (PET), the most frequent is the use of 18F-fluorodeoxyglucose (18F-FDG) demonstrating the turn-over of glucose exploitation in a manner of Warburg phenomenon. Even tumor cells can undergo metabolic reprogramming by changing the expression of glycolysis-related proteins, development of hypoxic condition increases glucose uptake to promote their growth. The hypoxic conditions are stimulation also the development of drug and/or radiation resistance, thus, the identification of the hypoxic tissue could play an important role in therapy planning. The process that enables use of hypoxia specific PET radiopharmaceutical starts when it enters cell by passive diffusion. Intracellularly, a model substance - 18F-fluoromisonidazol (18F-FMISO) is reduced by nitroreductase enzymes to become trapped in cells within reduced tissue oxygen partial pressure. The identification of the hypoxic tissue aids to plan the target to radiotherapy in squamous cell carcinomas of head and neck or cervical carcinoma, when 18F-FMISO-PET/CT is used as a planning procedure for a target volume, while 18F-FDG-PET/MRI is being the local and whole body staging procedure. Hypoxia imaging helps to identify the high-grade component of an astrocytic tumor before stereotactic biopsy.

P-238 Pattern of failure after radiotherapy for squamous cell carcinoma of the anus

Squamous cell carcinoma of the anus (SCCA) is primarily treated with radiotherapy (RT). Treatment failure is predominantly locoregional within the pelvic area. Information on the pattern of failure is important when optimizing treatment strategies. The aim of this study was to evaluated pattern of failure and outcome after radiotherapy for SCCA. A single center, retrospective study was conducted, including patients with histopathological proven SCCA diagnosed between 1998 and 2018 and treated with RT with curative intention. Data was collected from medical records and included patient-, disease-, and treatment characteristics, and outcome data. Disease stage was reclassified according to the 8th edition of the TNM staging system. Locoregional failure (LRF) was defined as failure within the pelvis, and distant failure (DF) as failure outside the pelvis. Survival data were estimated using the Kaplan-Meier method. In total 420 patients treated with curative RT were identified. Median age was 60 years (range 28-89), 75.0% were female, 68.8% had T1-T2 tumors, and 30.9% were diagnosed with lymph node (LN) positive disease. All patients received RT, RT only (79.8%) or with concomitant chemotherapy (19.3%), further 30.7% received induction chemotherapy. Treatment planning was done with IMRT/VMAT in 76.4% of cases, and median prescribed dose to tumor was 64Gy (range 45-64), 64Gy (range 50-64) to pathological LN and 51.2Gy (range 39-54) to the elective nodal areas. Median follow-up (FU) time was 6.1 years (range 0.05-23.6). Overall survival for all stages at 3- and 5 years was 84.0% and 75.5%, respectively and disease-free survival was 73.2% and 69.9% at 3 and 5 years. 85.9% (n=361) achieved complete response (CR) after RT whereas 13.8% (n=58) was diagnosed with progressive or persistent disease, of whom 94.8% had salvage surgery performed. Of patients with CR after RT 19.1% (n=69) experienced treatment failure during FU. As first site of recurrence 13.0% had LRF (n=47), 5.0% had DF (n=18), and 1.1% had both LRF and DF (n=4). When combining both persistent disease and later recurrence 30.2% experience treatment failure. In general, few regional LN recurrences were observed (1.7% of first failures including 0.6% with LN only failures). Recurrence in regional LN was located to the mesorectal LN (n=2), inguinal LN (n=3) or iliac LN (n=1). DF as first site of failure was seen in 22 cases (6.1%) located to either the lung (n=11), liver (n=7) distant LN (n=8), bone (n=1), brain (n=1) or other (n=2) with 8 patients having failure to more than one site. When looking at subsequent failures DF was seen in further 14 cases with a total DF rate of 8.6%. Recurrences to regional LN and DF were low, and the majority of recurrences were thus located within the standard irradiated area. Consequently, it is highly relevant to investigate the exact anatomical location and its relation to specific treatment dose. A dose-mapping study is therefore ongoing.

Post-radiation Osteosarcomas of the Jaws and a Review of the Literature

Patients with a primary malignancy have a 1.29 times increased risk for developing a second malignancy compared to people with no history of malignancy. Radiation is an effective treatment for malignancies but is also known to induce tumor formation. The most common radiation induced sarcomas (RIS) include fibrosarcoma, chondrosarcoma, malignant fibrous histiocytoma and osteosarcoma. Radiation induced sarcomas of the head and neck are rare and are associated with poor long-term prognosis. The most common sites in the head and neck are the paranasal sinuses and nasal cavity, neck and mandible. Cahan's criteria for diagnosis of radiation induced sarcomas include history of radiation, latency period of several years, occurrence of sarcoma in the field of irradiation, and histologic confirmation. An approximate dose of 30Gy is known to induce RIS. A latency period of 10-12 years is supported by the literature. Between the years of 1986 to 2020 the Oral Pathology Lab at New York Presbyterian Queens diagnosed 29 cases of osteosarcoma, 10 cases of chondrosarcoma, and 9 cases of MFH. Only 6 of the 48 sarcoma cases were radiation induced and all of them were osteosarcomas. The mean age of the 6 osteosarcomas was 52.83 years. All our cases were in males. Based on past medical history 5 of the cases received radiation for squamous cell carcinoma and 1 for Hodgkin Lymphoma. Of the 4 cases with documented radiation timelines, a mean latency period of 11.87 years was identified. The submitting surgeons suspected malignancy in 5 cases based on clinical appearance. The literature states RIS usually occurs in bone, however, 5 of our cases occurred in soft tissue within the radiation field. Histologically, cases showed malignant spindle cells producing osteoid matrix except case 1 in which the tumor cells embedded in eosinophilic hyalinized stroma demonstrated SATB2 nuclear expression, supporting osseous differentiation.

Definitive radiotherapy for squamous cell carcinoma of the oral cavity: a single-institution experience.

BackgroundSurgery is standard of care for oral cavity cancer (OCC). We provide a single-institution experience using definitive radiotherapy (RT) with or without concurrent systemic therapy for primary unresectable OCC.Patients and methodsWe retrospectively examined 49 patients with non-metastatic primary unresectable OCC treated with definitive RT between 2000 and 2019. The majority of patients (63.3%) were treated with definitive chemoradiotherapy while 26.5% were given single-agent cetuximab weekly simultaneous to definitive RT. Five patients were treated with definitive RT alone because of limited disease and no nodal involvement.ResultsMedian follow-up was 73 months (range, 6–236 months), median progression free survival (PFS) was 42 months (range, 2–157 months), median local disease-free survival (LDFS) was 44 months (range, 2–157 months) and median overall survival (OS) from the time of RT initiation was 52 months (range, 5–236 months). There were 65.3% locoregional failures, 84.4% local and 15.6% distant metastasis. The majority of patients with local failure presented with American Joint Committee on Cancer (AJCC) Stage III–IV disease (59.2%). The 5-year Kaplan-Meier estimates for OS (III–IV vs. I–II) was 22.8% vs. 54.2 % (p = 0.03, HR 2.090, 1.1–4.2). Patients who were treated with systemic therapy had a significant better 5-year overall survival compared to those with RT alone (43.9% vs. 23.1%, p = 0.05, 1.0–4.1). RT with doses less than 70 Gy (p = 0.046, HR 2.1 (1.0–4.5) was associated with worse overall survival. Mucositis was the most common ≥ grade 3 acute toxicity and occurred in 19 patients (39%). Incidences of chronic toxicities were loss of taste, trismus, osteoradionecrosis and xerostomia.ConclusionsDefinitive RT with or without concurrent systemic agents in patients with unresectable OCC resulted in an eloquent rate of locoregional control and good overall survival rates and is currently the best available treatment option in this patient collective.

Radiation-Associated Sarcoma of the Head and Neck: Incidence, Latency, and Survival.

Radiation-associated sarcomas of the head and neck (RASHN) are known but rare sequelae after radiation for squamous cell carcinoma. The purpose of this study was to characterize RASHN, estimate the risk of RASHN in head and neck squamous cell patients after therapeutic radiation, and compare their survival to that of patients with de novo sarcomas of the head and neck (dnSHN). Retrospective database analysis. RASHN and dnSHN cases were collected from the Surveillance, Epidemiology, and End Results Database to identify risk factors and calculate incidence and latency. Survival was compared between RASHN and dnSHN. The risk of RASHN was 20.0 per 100,000 person-years. The average latency period was 124.2 months (range 38-329). The cumulative incidence of RASHN at 20 years was 0.13%. Oral cavity and oropharynx primaries demonstrate increased risk. Five-year overall survival of RASHN was 22.4% compared to 64.5% for dnSHN. RASHN are confirmed to be rare. RASHN have poor overall survival and worse survival compared to dnSHN. The impact of intensity-modulated radiation therapy protocols on this risk is unknown. Modifiable risk factors of smoking and alcohol consumption continue to dwarf radiation therapy as risk factors of second primary head and neck cancers. 3 Laryngoscope, 132:1034-1041, 2022.

Sparing the Larynx and Hypopharynx With Radiotherapy for Squamous Cell Carcinoma of Unknown Primary Site and Predominant Adenopathy in Level IIA

There is controversy about the need to target the mucosa of the larynx and hypopharynx during radiotherapy (RT) for squamous cell carcinoma of unknown primary site (SCCA-UP). By 1997, the policy in our department was to target only the oropharynx and nasopharynx in patients with SCCA-UP metastatic to the level II cervical nodes. The purpose of this study is to report the rate of cancer recurrence in the larynx or hypopharynx using an approach that excluded these areas from the RT target volumes.We reviewed the medical records of patients who met the following inclusion criteria: received RT in our department for SCCA-UP between January 1, 1997, and December 31, 2019; no history of surgery that could disrupt the cervical lymphatics; predominant adenopathy in level IIA; and neck stage N1-2c. We excluded N3 because the incidental dose to the larynx and hypopharynx is usually high in patients with a > 6-cm nodal conglomerate. We calculated the following from the date of the last RT fraction: mucosal control to the date of first recurrence in a mucosal site in the head and neck; regional control with or without distant control to the date of first recurrence in ipsilateral or contralateral neck nodes with or without distant disease; distant control to the date of first documented metastatic lesion most likely originating from SCCA-UP; relapse-free survival to the date of recurrent disease at any site or death; cause-specific survival to the date of death due to SCCA-UP; and overall survival to the date of death from any cause.The study population included 50 patients with a median follow-up after RT of 7.1 years. No patient developed recurrent cancer in a mucosal site (0/50), 2% (1/50) developed a neck recurrence in a high-dose area with synchronous distant metastases, and 2% (1/50) developed distant metastases with no evidence of local or regional recurrence. At most recent follow-up, 70% (35/50) of patients were alive without evidence of recurrent SCCA-UP (NED), 4% (2/50) died of recurrent cancer, 22% (11/50) died of intercurrent disease (DID), and 4% (2/50) died of unknown causes (unknown).When delivering RT for SCCA-UP metastatic predominantly to level IIA, it is not necessary to target the mucosa of the larynx or hypopharynx. The extent to which the incidental RT dose to these areas contributes to cancer control is not evaluated in this study.

Clinical Factors Associated With Post-Treatment Aspiration in Patients Receiving Radiotherapy for Squamous Cell Carcinomas of the Head and Neck

Radiotherapy (RT) is an integral component of curative treatment of head and neck squamous cell carcinomas (HNSCC). Compromise of dysphagia/aspiration-related structures remains a clinically significant, and potentially life threatening, treatment complication. We hypothesized that treatment intensification might increase the long term risk of aspiration events, and investigated clinical factors contributing to this risk.A single institution database of patients who received curative-intent RT for HNSCC from 1996 to 2018 was queried. Included patients had laryngeal/hypopharyngeal, oral cavity, or oropharyngeal cancers and did not experience locoregional failure. An aspiration event was defined as aspiration on modified barium swallow, or aspiration pneumonia, > 3 months after RT. 324 patients were eligible, with a median follow up of 42 months (range 4-195). Independent variables investigated included age, primary site, sex, T stage, N stage, overall stage, IMRT vs 3D RT, standard vs altered fractionation, prior vs never smoker, definitive vs post-operative RT, and the use of chemotherapy with RT. Univariate logistic regression was used to identify statistically significant risk factors and multivariate regression was then used to derive the final model. Kaplan Meier analysis was used to assess time to last aspiration event; significance was assessed via the log-rank test.On univariate analysis patients who received chemotherapy (P = 0.007), were treated using 3D RT (P = 0.0009), or were prior smokers (P = 0.02) had a significantly increased risk of an aspiration event. No differences were seen with respect to age, sex, site, overall stage, T stage, N stage, postoperative vs definitive therapy, or fractionation. On multivariate analysis the use of chemotherapy [P = 0.004, OR 3.5 (95% CI 1.5 - 8.2)] and prior smoking [P = 0.03, OR 2.7 (95% CI 1.1 - 6.7)] remained significantly associated with increased risk, while use of IMRT significantly diminished risk [P = 0.001, OR 0.35 (0.19 - 0.35)]. In patients who received chemotherapy, the actuarial risk of aspiration via Kaplan Meier was 24% at five years, as opposed to 8% for RT alone (P = 0.007). Of the six patients who died secondary to aspiration pneumonia, five received chemotherapy with RT.In this analysis the use of chemotherapy, prior smoking, and the use of 3D RT increased the odds of aspiration in patients receiving RT for HNSCC. Of note, use of chemotherapy increased this risk almost three-fold; this risk persisted long term, supporting the hypothesis that treatment intensification has a significant, persistent clinical impact on dysphagia-related structures. These data highlight the need to refine criteria for the use of chemotherapy with RT in the adjuvant setting, and support diminished dysphagia risk seen in de-intensification trials in HPV-associated oropharyngeal cancers.

Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival

AimsWe conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS). Materials and methodsSCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables. ResultsIn total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21–30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5–0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis. ConclusionA large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.

Unilateral versus bilateral nodal irradiation: Current evidence in the treatment of squamous cell carcinoma of the head and neck.

Cancers of the head and neck region often present with nodal involvement. There is a long-standing convention within the community of head and neck radiation oncology to irradiate both sides of the neck electively in almost all cases to include both macroscopic and microscopic disease extension (so called elective nodal volume). International guidelines for the selection and delineation of the elective lymph nodes were published in the early 2000s and were updated recently. However, diagnostic imaging techniques have improved the accuracy and reliability of nodal staging and as a result, small metastases that used to remain undetected and were thus in the past included in the elective nodal volume, will now be included in high-dose volumes. Furthermore, the elective nodal areas are situated close to the parotid glands, the submandibular glands and the swallowing muscles. Therefore, irradiation of a smaller, more selected volume of the elective nodes could reduce treatment-related toxicity. Several researchers consider the current bilateral elective neck irradiation strategies an overtreatment and show growing interest in a unilateral nodal irradiation in selected patients. The aim of this article is to give an overview of the current evidence about the indications and benefits of unilateral nodal irradiation and the use of SPECT/CT-guided nodal irradiation in squamous cell carcinomas of the head and neck.

POS-692 Euglycemic Diabetic Ketoacidosis Related to SGLT2 Inhibitor Use in Kidney Transplant Patient with Squamous Cell Carcinoma

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have renal protective effect in diabetic and non-diabetic patients with significant reduction of cardiovascular events. The data is emerging for the short-term efficacy and safety of SGLT2 inhibitor in diabetic kidney transplant patients. Diabetic ketoacidosis is a well recognized side effect of SGLT2i with variable predisposing factors. There is limited data regarding the use of SGLT2i in oncology patients. We described a case of diabetic kidney transplant patient on dapagliflozin who developed DKA during active therapy for squamous cell carcinoma. A 65 years old female, known to have hypertension and diabetes mellitus type 2 leading to end stage renal disease. She underwent living unrelated kidney transplantation in 2018. Her home medications included insulin glargine, dapagliflozin 10 mg, pantoprazole 40mg, prednisolone 7.5 mg daily, cyclosporine 125 mg q12 hours and atorvastatin 20mg. She was diagnosed with right inner cheek moderately differentiated keratinizing squamous cell carcinoma with submandibular lymphadenopathy (Stage: cT4aN2M0). She was initiated on concurrent chemotherapy (Cetuximab) and radiotherapy. Cycle 4 of therapy was complicated with poor oral intake and severe mucositis for 3 days prior to admission. She had evidence of acute kidney injury stage 1 in transplanted kidney (serum creatinine increased from baseline of 58 to 110 micromole/l). Other laboratory investigations revealed hyperkalemia 5.7mmol/l, metabolic acidosis 6mmol/l, high anion gap metabolic acidosis, normal lactate level, arterial PH of 7.1, ketones were positive in urine and blood glucose level of 12mmol/l. She was diagnosed with severe euglycemic diabetic ketoacidosis DKA, due to SGLT2i (dapagliflozin 10 mg) and starvation. She required critical care admission with rigorous IV hydration, insulin infusion per DKA protocol, IV sodium bicarbonate, IV hydrocortisone and IV cyclosporine. Her clinical condition improved by fifth day of critical care. Urinary tract infection and re-feeding syndrome post nasogastric enteral feeding complicated her hospital course. Dapagliflozin was held and next cycle of chemo-radiotherapy was delayed. Some of the potential risk factors for euglycemic DKA induced by SGLT2 inhibitors are infections, withdrawal of insulin, starvation, dehydration and acute kidney injury. The underlying pathophysiologic process of ketoacidosis induced by SGLT2 inhibitors is not well established. There are few case reports describing this complication in diabetic oncology patients, leading to discontinuation of the drug. The use of SGLT2 inhibitor is limited in diabetic kidney transplant patients and about 100 cases reported in literature without evidence of DKA in short-term follow up. To the best of our knowledge, this is the first case describing a successful management of dapagliflozin-induced euglycemic DKA in kidney transplant patient with squamous cell carcinoma. SGLT2 inhibitor associated eDKA is very rare in oncology patients and this is the first case reported in kidney transplant patient who was on active chemotherapy and radiotherapy for squamous cell carcinoma. We suggest to hold SGLT2i therapy during active oncology treatment especially in the setting on severe mucositis.