Sinonasal Cancer Research Articles

Nasal packing does not affect the dosimetry of sinonasal cancers treated with intensity-modulated radiotherapy or volumetric-modulated arc therapy

Introduction: To investigate the impact of nasal packing on radiotherapy dosimetry for nasal and paranasal sinus cancers treated with intensity modulate radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) technique. Methods: A prospective database identified all patients with primary nasal and paranasal sinus cancers treated with adjuvant radiotherapy. All patients were simulated using CT scanning with packing in the nasal cavity. For this study the nasal packing was contoured and assigned an electron density equivalent to air. The dose to the pre-operative gross tumour volume (GTV), planned tumour volume (PTV) and organs-at-risk (OAR) were re-calculated and compared to those with nasal packing, using both the Pinnacle (Collapsing Cone Convolution) and Monaco (Monte Carlo) planning systems. Results: 24 patients were identified, predominantly ethmoid (14) or maxillary (4) primaries. The predominant histology was SCC (12/24). The majority (22/24) were treated with curative intent. Using Collapsing Cone Convolution calculation, the median [range] coverage of 95% of prescribed dose to high-dose PTV (95.5% [92.2-98.5%] vs 95.2% [92.1-98.5%]; packing vs no packing, P=1.00) and low-dose PTV (95.8% [90.0-99.4%] vs 95.9% [91.1-99.7%]; packing vs no packing, P=1.00) were not impacted by packing the nasal cavity. There was also no impact by no packing on the maximal dose to the brainstem, optic nerves, optic chiasm nor lens. Conclusions: Packing of nasal cavity does not change the dose to the PTVs or critical OARs in patients with nasal and paranasal sinus cancers treated with adjuvant IMRT or VMAT radiotherapy and can be safely omitted.

Attributable Fraction of Cancer Related to Occupational Exposure in Italy.

Exposure to occupational carcinogens is an important and avoidable cause of cancer. We aimed to provide an evidence-based estimate of the burden of occupation-related cancers in Italy. The attributable fraction (AF) was calculated based on the counterfactual scenario of no occupational exposure to carcinogens. We included exposures classified as IARC group 1 and with reliable evidence of exposure in Italy. Relative risk estimates for selected cancers and prevalences of exposure were derived from large-scale studies. Except for mesothelioma, a 15-20-year latency period between exposure and cancer was considered. The data on cancer incidence in 2020 and mortality in 2017 in Italy were obtained from the Italian Association of Cancer Registries. The most prevalent exposures were UV radiation (5.8%), diesel exhaust (4.3%), wood dust (2.3%) and silica dust (2.1%). Mesothelioma had the largest AF to occupational carcinogens (86.6%), followed by sinonasal cancer (11.8%) and lung cancer (3.8%). We estimated that 0.9% of cancer cases (N~3500) and 1.6% of cancer deaths (N~2800) were attributable to occupational carcinogens in Italy. Of these, about 60% were attributable to asbestos, 17.5% to diesel exhaust, followed by chromium and silica dust (7% and 5%). Our estimates provide up-to-date quantification of the low, but persistent, burden of occupational cancers in Italy.

Trends in the incidence of head and neck cancer: A nationwide population-based study

ObjectiveThis study aimed to demonstrate the temporal trend in incidence of head and neck cancer (HNC) in Taiwan. Materials and methodsPatients with a HNC were retrieved from the Taiwan’s Health Insurance Database. We identified 16,894 patients aged ≥20 years who had received a first-time diagnosis of cancer of the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, sinonasal, salivary gland or thyroid gland between 2010 and 2018. We calculated the annual incidence rate per 100,000 population, overall, and classified by gender and cancer type. We also used the annual percent change (APC) to characterize trends in head and neck cancer rates over time. ResultsThe incidence rate showed a gradual decline during this period from 2010 to 2018 with an APC of −2.81% (p < 0.001). Within gender groups, the decline was not statistically significant among females (APC = −1.69, 95% CI = −3.58 ∼ 0.23, p = 0.080). Within cancer types, strikingly high magnitude and statistically significant declines were observed in respect of cancer of the nasopharynx (APC = −7.89%, 95% CI = −9.43%∼−6.31%, p < 0.001), sinonasal cancer (APC = −10.08%, 95% CI = −16.66%∼−2.99%, p = 0.012) and oropharyneal cancer (APC = −9.47%, 95% CI = −15.15%∼−3.42%, p = 0.013) over the study period. In contrast, there was a statistically significant increase in incidence on thyroid cancer over the study period with an APC of 4.75% (95% CI = −2.81%∼6.75%, p < 0.001). ConclusionsHNCs in Taiwan are showing a decreasing trend, led by the upper respiratory and oropharyngeal cancers. However, there was a concurrent increasing trend of the incidence on thyroid cancer. These trends may be attributable to changing lifestyles and behavioral choices in Taiwan.

The SINTART 1 study. A phase II non-randomised controlled trial of induction chemotherapy, surgery, photon-, proton- and carbon ion-based radiotherapy integration in patients with locally advanced resectable sinonasal tumours

PurposeSinonasal tumours are rare diseases with poor prognosis. Multimodal approach including surgery is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment—induction chemotherapy (ICT), surgery and radiotherapy (RT)—modulated by histology and response to ICT. MethodsPatients with untreated, operable sinonasal tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enrolled in a single-arm, phase II, multicenter clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype, followed either by curative chemo-RT for pts with ≥80% reduction of initial tumour diameter or surgery and adjuvant (chemo)RT. Photon and/or proton/carbon ion-based RT was employed according to the disease site and stage. Primary end-point was 5-year progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate (ORR) per RECIST 1.1 and safety. ResultsThirty-five patients were evaluable for primary end-point. Fourteen patients (40%) were treated with definitive (CT)RT and 20 (57%) underwent surgery. Five-year PFS was 38% (95% confidence interval [CI], 21–69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28–75), with a median OS of 36 months. Three-year PFS—OS for pts achieving PR/CR versus stable disease (SD)/PD to ICT were 49.8–57% versus 43.2–53%, respectively. Three-year PFS for patients achieving major volumetric partial response (≥80% reduction of initial tumour volume, major partial volumetric response [mPRv]) versus non-mPRv were 82% versus 28% and 3-year OS were 92% versus 36% (p value 0.010 and 0.029, respectively). The ORR to ICT was 54% and 60% across all histotypes and in the sinonasal undifferentiated carcinoma (SNUC) subpopulation, respectively, with 6/15 SNUCs (40%) achieving mPRv. ConclusionTreatment of advanced sinonasal cancer with histology-driven ICT followed by (CT)RT in responsive patients was feasible. Overall, these findings suggest a possible role of ICT as the primary approach in newly diagnosed, resectable sinonasal tumours—especially SNUC—to select patients with favourable prognosis. Histology heterogeneity limits generalisation of trial results.

Abstract 6077: Comprehensive multi-omic characterization of genetic changes associated with sinonasal squamous cell carcinoma progression

Abstract Approximately 50-80% of sinonasal tract cancers are sinonasal squamous cell carcinoma (SNSCC), a rare malignancy which occur in the nasal cavity and maxillary sinus. These lesions possess a propensity for local invasion into adjacent structures including the skull base, brain, and orbit. Owing to relatively mild symptoms during early stages, which resemble benign sinonasal disease, most patients are already in clinically advanced stages when diagnosed. Therefore, despite improvements in endoscopic surgical approaches, radiotherapy and imaging techniques, the 5-year overall survival for advanced SNSCC patients remains poor (~40%). Inverted sinonasal papilloma (IP) is a locally aggressive, benign epithelial neoplasm arising in the paranasal sinuses which has a high recurrence rate and transforms to SNSCC in 10%-25% of cases. As some IP evolve to malignant neoplasms, it has been presumed that they represent an intermediate step in SNSCC progression. However, the current tools for detecting altered epithelial cells, such as clinical examination and histological characteristics, have limited prognostic value for predicting which IP will progress to malignancy, and the link between IP and invasive disease remains unclear. Activating mutations in EGFR and PIK3CA genes as well as loss-of-function mutations in TP53 have been reported in a few very small cohorts of IP and SNSCC lesions, suggesting their role in IP pathogenesis and progression to invasive malignancy. Other observed alterations potentially associated with malignant transition include KRAS mutations, loss of heterozygosity (LOH) at the 9p21 locus (containing p16INK4a), mismatch repair genes deficiency, amplification of FGFR1 and SOX2 genes, as well as NFκB, COX2 and HOXA9 overexpression. While these studies provide a snapshot of molecular changes in SNSCC, genetic alterations critical to the development of SNSCC are poorly understood, and the exact mechanism underlying malignant transformation remains unknown. In this study we have used PandaOmic, a multi-omic data analysis and visualization algorithm, to perform a first comprehensive integrative analysis of WES, mitochondrial sequencing and transcriptomic data obtained from 11 IP lesions, matched invasive SNSCC tumors and histologically normal paranasal sinus epithelium collected from the same patients. Our analysis reveals heterogeneous mutational patterns, gene expression changes and signaling pathways features associated with SNSCC pathogenesis, and provides crucial insights that may aid in the development of novel means of prevention, diagnosis, and treatment of this rare, aggressive and poorly characterized malignancy. Citation Format: Alka Singh, Nikita Babushkin, Michael Korzinkin, Viktoria Sarkisova, Vasudha Mishra, Ari Rosenberg, Mark Lingen, Justin Bishop, Alex Zhavoronkov, Nyall London, Nishant Agrawal, Xuanyao Liu, Evgeny Izumchenko. Comprehensive multi-omic characterization of genetic changes associated with sinonasal squamous cell carcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6077.

Particle Reirradiation of Malignant Epithelial and Neuroectodermal Sinonasal Tumors: A Case Series from CNAO

Sinonasal cancers (SNCs) are rare and heterogeneous in histology and biological behavior. The prognosis is generally unfavorable, especially in inoperable cases. In recent years, for some histologies, such as undifferentiated sinonasal carcinoma (SNUC), multimodal treatment with a combination of induction chemotherapy, surgery, and chemo/radiotherapy (RT) has improved the prognosis. Nevertheless, still about half of the patients treated incur a recurrence, in most of the cases at the local site. Surgery with and without RT is usually the treatment choice in cases of recurrence after previous RT in combination with systemic therapy or RT in a histology-driven fashion. In the case of inoperable disease or contraindications to surgery, RT is still a valid treatment option. In this context, hadron therapy with protons (PT) or carbon ions (CIRT) is often preferred due to the physical and biological characteristics of charged particles, allowing the administration of high doses to the tumor target while sparing the surrounding healthy tissues and potentially limiting the side effects due to the high cumulative dose. In the absence of a standard of care for the recurrent setting, we aimed to investigate the role of re-RT with PT or CIRT. We retrospectively analysed 15 patients with recurrent, previously irradiated, SNCs treated at our institution between 2013 and 2020. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Acute and late toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events CTCAE version 5.0. A total of 13 patients received CIRT and 2 patients received PT. The median re-RT dose was 54 GyRBE (range 45-64 GyRBE) delivered in 3 or 4 GyRBE/fr (fraction) for the CIRT, and 2 Gy RBE/fr for the PT schedule. LC was 44% at the 1-year follow-up and 35.2% at the 3-year follow-up. OS at 1 and 3 years were 92.9% and 38.2%, respectively. Fourteen patients developed G1-G2 acute toxicity (dermatitis and mucositis), and no patients developed G3-G5. Regarding late toxicity, 10 patients encountered at maximum G1-2 events, and 4 did not experience any toxicity. Only for one patient G3 late toxicity was reported (dysphagia requiring a percutaneous endoscopic gastrostomy).

Aspergillus Species and Human Papillomavirus Infections in Epithelial Tumors of Nasal and Paranasal Cavities

Background: There are diverse lesions originating from the paranasal sinuses and nasal cavity. Tobacco use, alcohol consumption, and malnutrition have been identified to play a role in the development of head and neck carcinomas. Recently, fungi and viruses have been recognized as potential causes of nasal cavity and paranasal tumors. Objectives: This study aimed at specifying the prevalence of Aspergillus and human papillomavirus (HPV) infections in the epithelial tumors of nasal cavity and paranasal sinuses. Methods: In this cross-sectional study, 57 paraffin-embedded tissue samples of malignant and benign lesions of the paranasal sinuses and nasal cavity were evaluated for the presence of Aspergillus and HPV DNA by nested polymerase chain reaction (nPCR) technique with specific primers. Results: Despite the absence of angular hyphae (acute angle) of the fungus on histopathological slides, overall, 10 (17.54%) out of 57 paraffin-embedded samples were found to be positive for Aspergillus species. However, HPV-DNA was not found in any of the samples. Conclusions: Our data suggest that fungal infections (especially aspergillosis) as an etiological factor can be contributed to the development of sinonasal cancer and, therefore, they should be considered in the management of patients with sinonasal cancer. In addition, PCR can provide an alternative to culture-dependent identification methods.

22O Sinonasal cancer: Molecular biomarkers for tumor classification and targeted treatment

22O Sinonasal cancer: Molecular biomarkers for tumor classification and targeted treatment

High-risk human papillomavirus 16/18 associated with improved survival in sinonasal squamous cell carcinoma.

There has been conflicting evidence on the independent prognostic role of human papillomavirus (HPV) status in sinonasal cancer. The objective of this study was to assess whether the survival of patients with sinonasal cancer differs based on various HPV statuses, including HPV-negative, positive for the high-risk HPV-16 and HPV-18 (HPV16/18) subtypes, and positive for other high-risk and low-risk HPV subtypes. In this retrospective cohort study, data from the National Cancer Database were extracted from the years 2010-2017 for patients who had primary sinonasal cancer (N = 12,009). The outcome of interest was overall survival based on HPV tumor status. Study included an analytic cohort of 1070 patients with sinonasal cancer who had confirmed HPV tumor status (732 [68.4%] HPV-negative; 280 [26.2%] HPV16/18-positive; 40 [3.7%] positive for other high-risk HPV; and 18 [1.7%] positive for low-risk HPV). HPV-negative patients had the lowest all-cause survival probability at 5 years postdiagnosis (0.50). After controlling for covariates, HPV16/18-positive patients had a 37% lower mortality hazard than HPV-negative patients (adjusted hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82). Patients aged 64-72 years (crude prevalence ratio, 0.66; 95% CI, 0.51-0.86) and 73 years and older (crude prevalence ratio, 0.43; 95% CI, 0.31-0.59) presented with lower rates of HPV16/18-positive sinonasal cancer than those aged 40-54 years. In addition, Hispanic patients had a 2.36 times higher prevalence of non-HPV16/18 sinonasal cancer than non-Hispanic White patients. These data suggest that, for patients with sinonasal cancer, HPV16/18-positive disease may confer a significant survival advantage compared with HPV-negative disease. Other high-risk and low-risk HPV subtypes have survival rates similar to the rates for HPV-negative disease. HPV status might be an important independent prognostic factor in sinonasal cancer that could be used in patient selection and clinical decisions.

Incidence, risk factors, and prognostic value of nodal involvement in sinonasal cancers.

Incidence, risk factors, and prognostic value of nodal involvement in sinonasal cancers.

Molecular Evidence for Olfactory Neuroblastoma as a Tumor of Malignant Globose Basal Cells

Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.

Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms-A Systematic Review.

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

The Role of Induction Therapy for Sinonasal Cancers.

The role of induction chemotherapy in sinonasal cancers is promising; however, prospective studies with higher grades of evidence are needed. With the currently available literature, the authors would advocate for the use of induction chemotherapy (IC) in locally advanced sinonasal squamous cell carcinoma (T3-T4) for organ preservation and potentially for improved survival outcomes. In sinonasal undifferentiated carcinoma (SNUC), IC should be considered in all patients given its tendency for aggressive invasion and poor outcomes. In SNUC, response to IC may direct the modality of definitive treatment to follow. In responders (partial or complete), chemoradiation therapy should be strongly considered. In non-responders or in those with progression of disease, surgical therapy is favored. For esthesioneuroblastoma, surgical resection with negative margins and adjuvant radiation therapy remains the gold standard. However, IC may be considered for locally advanced disease especially with orbital invasion or in recurrent/distant disease. There is no definite indication for IC in sinonasal adenoid cystic carcinoma or sinonasal adenocarcinoma. Recommendations are summarized in Table 1.

Implications of diabetes in head and neck cancer - A single center real-world data.

Diabetes mellitus (DM) and altered glucose metabolism have been associated with carcinogenesis, but also with prognosis and tolerance to treatment in different types of cancer. Head and neck cancers (HNC), the sixth most common malignancy worldwide, require a multimodal approach, especially in advanced stages and cancer specific treatment is often associated with therapeutic failure and severe toxicities even if it is delivered according to current standards. The aim of the study was to evaluate the clinical, biological and outcomes implications of DM in patients with HNC. The cases diagnosed with HNC associated with DM between January 2008 and December 2016 were selected from the database of the oncology clinic and the oncology outpatient clinic of the Craiova County Hospital. Under the limits of a relatively reduced patient lot of 23 cases, certain particular aspects of these cases are highlighted possibly due to the association of DM with HNC. This category of patients should not be treated differently even if a precaution is necessary due to the increased risk of complications related to treatment. The use of Metformin could bring outcome benefit and the treatment of DM with insulin could be associated with a worst prognostic. The use of poly-chemotherapy regimens (platinum double or triple combination including platinum salts) demonstrates the feasibility of using chemotherapy for these subtypes of patients. A tendency to de-escalate the treatment by omitting radiotherapy for this category of patients should also be noted. Neutrophil to lymphocyte ratio (NLR), a less specific biomarker could be less useful than the Glasgow Prognostic Score (GPS) which can be considered an accessible biomarker. A large percent of sinonasal cancers compared to the data reported in the literature could be also related to DM. Both this possible association and the benefit of Metformin and 5-Flurouracil must be reevaluated in studies in larger groups of patients (Ref. 25). Keywords: diabetes, head and neck cancers, metformin, toxicity, outcomes, chemotherapy.

Sinonasal adenocarcinomas: Retrospective analysis from an oncology center

Introduction and objectivesSinonasal adenocarcinomas are rare and heterogeneous tumors and for this reason remain understudied. Our purpose is to analyze clinical presentation, outcomes and factors affecting survival of patients with sinonasal adenocarcinomas, treated at our institution. Material and methodsRetrospective review of clinical records of patients with sinonasal adenocarcinoma, treated at a tertiary oncology institution (January 2010 to December 2019). ResultsSixty patients diagnosed with adenocarcinoma were included, with male preponderance (54.90%) and a mean age of 57.5±14.9 years. Adenocarcinoma was the most frequent type of sinonasal cancer, contrary to previous reports from our institution. In most patients, it was detected at an advanced disease stage, significantly decreasing their survival rate when compared to patients diagnosed at initial stages (p<0.029). Intestinal type adenocarcinoma was established in 47 patients, the most frequent being the colonic subtype (24%). Tumors with good/moderate histologic differentiation presented a survival advantage over those that were poorly differentiated (p=0.043). The most common treatment modality was surgery followed by radiotherapy. Endoscopic resection was performed in 53% of the patients and an external approach was used in 40% of the patients. Estimated overall survival rates at 3 and 5-years were 64% and 53%, respectively, and cancer specific survival 72% and 65%, for the same period. Recurrence rate was 32% and occurred mainly locally. Disease Free Survival rate was 71% at 3 years and 65% at 5 years. ConclusionsDespite being the most common sinonasal malignancy in our sample, in contrast to other series, sinonasal adenocarcinomas are still rare tumors with a substantial local failure rate of around 30%. Advanced stage at diagnosis and histologic differentiation grade negatively affected prognosis of these tumors.

Effect of sarcopenia on survival outcomes in patients with nasopharyngeal and sinonasal cancer.

Effect of sarcopenia on survival outcomes in patients with nasopharyngeal and sinonasal cancer.

Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers

This prospective observational study examines if circulating tumor human papillomavirus DNA can be used as an accurate measure of disease status at the time of diagnosis, throughout treatment, and during monitoring in human papillomavirus-associated sinonasal and nasopharyngeal squamous cell carcinomas.

Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers.

Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.

O2.3 Detection and monitoring of circulating tumor HPV DNA in HPV-associated sinonasal and nasopharyngeal cancers

O2.3 Detection and monitoring of circulating tumor HPV DNA in HPV-associated sinonasal and nasopharyngeal cancers

Patterns of Failure in Sinonasal Cancers after Curative Intensity Modulated Radiation Therapy

<h3>Purpose/Objective(s)</h3> To study the pattern of failure in sinonasal cancers treated with curative intent radiotherapy using IMRT/ VMAT techniques, with or without chemotherapy. and also, to document the disease outcomes and toxicity. <h3>Materials/Methods</h3> Patients with sinonasal cancers who had been treated with curative intent radiation therapy using IMRT/ VMAT technique at our institute between January 2007 to December 2019 were evaluated. All demographic, disease, treatment and outcomes related details were retrieved from the electronic medical records (EMR), radiation oncology information system (ROIS) and treatment planning system (TPS). Locoregional failure (LRF) was defined either as persistent disease post treatment less than 6 months or reappearance of tumor at either primary site or draining regional lymph-nodes which was histologically or radiologically proven. MRI/PET-CT done at the time of recurrence was imported into the TPS and volume of failure (Vf) was contoured slice by slice. Overlap volume between Vf and 95% isodose of PTV1/PTV2/PTV3 was generated using Boolean tool in TPS. Failure was defined as in-field if >95% volume of recurrent tumor fell within the 95% isodose line of PTV1, marginal if 20- 95% of the volume of recurrence was within the 95% isodose line and outfield if <20% of the recurrent tumor was in the 95% isodose line of PTV1. Similar definitions were considered for PTV2 and PTV3 if any. Treatment related toxicity and control rates were also documented. <h3>Results</h3> A total of 126 patients were treated with IMRT of which 39 patients developed recurrences either at local, regional or distant sites. Of these 28 patients had developed LRF with or without distant metastases while 11 patients had distant metastases alone. Imaging at recurrence was available in 19/28 patients with LRF which forms the cohort for the present study. Eight of these patients had persistent residual disease at primary, 2 patients had local recurrence only, 2 patients had local and regional recurrence,7 patients had a regional recurrence. In patients with local failure 6 had in- field failure, 5 patients had marginal and 1 patient had out of field failure. Four of 5 patients with marginal recurrence had recurrence and PTV close to the critical structures resulting in compromised doses. All the regional recurrences were out of field failure in un-irradiated neck. However, there was no difference in regional failure in irradiated vs non-irradiated neck (p=0.73). The median follow-up of the entire cohort was 42.5 months. The 5-year OS, DFS, LC, RC and LRC were 74.4%, 62%, 76.8%, 89.1% and 69.6% respectively. The grade 3 and grade 4 late ocular toxicity were 4.8% (n=6) and 1.6%(n=2), respectively. <h3>Conclusion</h3> Local recurrence with in-field recurrence was the most common type of failure. Majority of the marginal failures were close to the critical structures. All the regional recurrences were observed in the unirradiated neck.