Squamous cell carcinoma of the nasal vestibule in the Netherlands: A clinical and epidemiological review of 763 cases (2008-2021).

BACKGROUND: Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare disease, distinctly different in presentation, treatment, and outcome from squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses. However, these are often not analyzed separately. METHODS: The Netherlands Cancer Registry (NCR) and pathology reports from the Dutch Nationwide Pathology Databank (PALGA) were used to identify all newly diagnosed SCCNV cases in the Netherlands between 2008 and 2021. RESULTS: A total of 763 patients were included. The yearly incidence rate displayed a significant downward trend with an annual percentage change (APC) of -3.9%. The 5-year overall survival (OS) and disease-free survival were 69.0% and 77.2%, respectively. The 5-year relative survival was 77.9% and improved slightly over the inclusion period. OS for patients who were staged cT3 appeared to be worse than those staged cT4a, calling the applicability of the TNM-classification into question. CONCLUSION: SCC of the nasal vestibule is rare, with declining incidence rates. Introducing a specific topography code for SCCNV is recommended to enhance registration accuracy. The TNM classification seems poorly applicable to SCCNV, suggesting the need to explore alternative staging methods.

Squamous Cell Carcinoma of the Nasal Vestibule: A Multi-Centric Observational Cohort Study.

OBJECTIVES: Squamous cell carcinoma of the nasal vestibule (NV-SCC) is a rare but challenging entity, due to the complex anatomy of the region. Consensus on the best treatment strategy is still lacking, as well as a dedicated staging system. Our aim was to analyze oncological outcomes of surgically treated patients and to investigate possible prognostic factors. METHODS: We performed a retrospective multi-centric observational study including six Academic Hospitals over a 10-year period, including only patients who underwent upfront surgery for primary NV-SCC. Patients were staged according to all currently available staging systems. The Kaplan-Meier method was used to compute overall, disease-free, and disease-specific survival. Logistic regression models were used to correlate between survival outcomes and clinical and pathological variables. RESULTS: Seventy-one patients with a median follow-up of 38 months were included in the study. Partial and total rhinectomy were the most commonly performed procedures, respectively, in 49.3% and 25.4% of cases. Neck dissection was performed on 31% of patients, and 45.1% of them underwent adjuvant radiotherapy. Three years overall, disease-specific and disease-free survival were, respectively, 86.5%, 90.3%, and 74.2%. None of the currently available staging systems were able to effectively stratify survival outcomes. Factors predicting lower overall survival on multivariate analysis were age (p = 0.021) and perineural invasion (p = 0.059), whereas disease-free survival was negatively affected by age (p = 0.033) and lymphovascular invasion (p = 0.019). CONCLUSION: Currently available staging systems cannot stratify prognosis for patients who underwent surgery for NV-SCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2634-2645, 2024.

Long-Term Outcomes of Olfactory Neuroblastoma: MD Anderson Cancer Center Experience and Review of the Literature.

OBJECTIVES/HYPOTHESIS: Olfactory neuroblastoma (ONB) is a rare sinonasal malignant neoplasm that is known to develop late recurrence. The aim of this study is to evaluate the long-term outcomes of patients with ONB and to determine the factors associated with prognosis. STUDY DESIGN: Retrospective study. METHODS: A retrospective review of the medical records of 139 patients diagnosed with ONB at MD Anderson Cancer Center was performed between 1991 and 2016. Descriptive statistics were calculated, and Kaplan-Meier curves were utilized to assess survival. RESULTS: Median follow-up time was 75 months. Overall, 129 patients (92.8%) had surgery as part of their treatment and 82 (58.9%) patients received postoperative radiation therapy (PORT) or concurrent chemoradiotherapy. Endoscopic approaches were utilized for 72 patients, 69.4% of whom had pure endoscopic endonasal approaches. Five-year overall survival and disease-specific survival were 85.6% and 93.4%, respectively. Recurrence rate was 39.6% with a median time to recurrence of 42 months. Among the 31 patients who received elective nodal irradiation (ENI), two patients developed neck recurrence (6.4%) compared with 20 who developed neck recurrence when ENI was omitted (34.4%) (P = .003). Advanced Kadish stage, orbital invasion, intracranial invasion, and presence of cervical lymphadenopathy at the time of presentation were significantly associated with poor survival. CONCLUSION: ONB has an excellent survival. Surgical resection with PORT when indicated is the mainstay of treatment. Endoscopic approaches can be used as a good tool. Elective neck irradiation reduces the risk of nodal recurrence among patients with clinically N0 neck. Despite the excellent survival, recurrence rate remains high and delayed, highlighting the need for long-term surveillance. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 132:290-297, 2022.

Outcomes of sinonasal oncocytic papilloma by endoscopic approach in 69 patients.

OBJECTIVE: Sinonasal oncocytic papilloma (SOP) is a rare subtype of sinonasal papilloma. There are currently few reports on its clinical features and outcomes after endoscopic surgical resection. This study aims to explore the clinical characteristics of SOP and potential factors predicting tumor recurrence through a single-center retrospective case series analysis. METHODS: We conducted a retrospective analysis of 69 patients who underwent endoscopic surgery of SOP from June 2012 to April 2019. The data of patients' demographics, clinical features, follow-up period, and treatment outcomes were collected. RESULTS: The series includes 43 males and 26 females with an average age of 60.2 years. The tumor commonly involved the nasal cavity (n = 59; 89.4%), followed by maxillary sinus (n = 31; 44.9%), ethmoid sinus (n = 28; 40.6%), frontal sinus (n = 6; 8.7%) and sphenoid sinus (n = 6; 8.7%). The follow-up period ranged from 3 months to 96 months (mean, 34.6 months) and nine patients (13%) developed tumor recurrence during the follow-up period. Univariate analysis found that the recurrence of SOP was significantly related to tumor attachment site, Oikawa tumor stage, and histological dysplasia (p<0.05). Multivariate COX regression analysis found that Oikawa staging system (p = 0.024) and presence of dysplasia (p = 0.04) were significantly related to tumor recurrence. CONCLUSION: SOP had low recurrence rate which was comparable to sinonasal inverted papilloma in the endoscopic era. Our findings also demonstrated that presence of dysplasia is an independent prognostic factor for recurrence free survival.

Absence of Survival Improvement for Patients with Esthesioneuroblastoma Over the Past 2 Decades: A Population-Based Study.

OBJECTIVE: Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we reviewed survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes. METHODS: We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A χ2 test was used to compare the categorical covariates and a t test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into 4 periods including 1998-2002, 2003-2007, 2008-2012, and 2013-2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test. RESULTS: ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared with patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages, whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past 2 decades, surprisingly, there has been no change in survival rates for patient with ENB (P = 0.793). CONCLUSIONS: Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

Model to predict cause-specific mortality in patients with olfactory neuroblastoma: a competing risk analysis.

PURPOSE: The main objective of this study was to evaluate the cumulative incidence of cause-specific mortality and other causes of mortality for patients with olfactory neuroblastoma (ONB). The secondary aim was to model the probability of cause-specific death and build a competing risk nomogram to predict cause-specific mortality for this disease. METHODS: Patients with ONB from 1975 to 2016 were identified from the Surveillance, Epidemiology, and End Results database. We estimated the cumulative incidence function (CIF) for cause-specific mortality and other causes of mortality, and constructed the Fine and Gray's proportional subdistribution hazard model, as well as a competing-risk nomogram based on Fine and Gray's model, to predict the probability of cause-specific mortality for patients with ONB. RESULTS: After data selection, 826 cases were included for analysis. Five-year cumulative incidence of cause-specific mortality was 19.5% and cumulative incidence of other causes of mortality was 11.3%. Predictors of cause-specific mortality for ONB included tumor stage, surgery and chemotherapy. Age was most strongly predictive of other causes of mortality: patients aged > 60 years exhibited subdistribution hazard ratios of 1.063 (95 % confidence interval [CI] 1.05-1.08; p = 0.001). The competing risk nomogram for cause-specific mortality was well-calibrated, and had good discriminative ability (concordance index = 0.79). CONCLUSIONS: We calculated the CIF of cause-specific mortality and other causes of mortality in patients with the rare malignancy ONB. We also built the first competing risk nomogram to provide useful individualized predictive information for patients with ONB.

Survival Outcomes of De Novo vs Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Importance: Overall, the prognosis of sinonasal squamous cell carcinoma (SCC) is poor. This malignancy can arise de novo or from inverted papillomas, but it is unclear whether survival differences between the 2 pathologies exist. Objective: To assess for survival differences between patients with sinonasal de novo SCC (dnSCC) and those with inverted papilloma-associated SCC (IPSCC). Data Sources: A search of Ovid MEDLINE, Embase, Scopus, and the Cochrane Library from inception to January 23, 2020, with cross-referencing of retrieved studies, was performed. Additional data were requested from authors. Study Selection: Inclusion and exclusion criteria were designed to capture studies with survival outcomes of adults with sinonasal SCC who underwent regular treatment. Clinical trials, cohort studies, case-control studies, and case series with more than 10 adults aged 18 years or older with sinonasal SCC were included. Exclusion criteria were studies on non-SCC sinonasal neoplasms, studies without histopathologic diagnoses, non-English language articles, nonhuman animal studies, and abstract-only articles. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) screened each abstract and full text, and a third investigator (J.J.L. or P.P.) adjudicated discrepancies. Of 729 unique citations, 26 studies of 1194 total patients were included. Data Extraction and Synthesis: Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed. The Methodological Index for Nonrandomized Studies (MINORS) criteria were used to assess study quality. Two blinded investigators (J.J.L., A.M.P., T.W.E., or N.S.W.) independently extracted data from each study. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was overall survival, and secondary outcomes were disease-free and disease-specific survival. Before data collection, it was hypothesized that the dnSCC cohort would have worse survival outcomes than the IPSCC cohort. Results: One study of patients with dnSCC, 12 studies of patients with IPSCC, and 5 studies with both cohorts were included in the meta-analysis of overall survival. The pooled 5-year overall survival rate for 255 patients with dnSCC was 56% (95% CI, 41%-71%; I2 = 83.8%) and for 475 patients with IPSCC was 65% (95% CI, 56%-73%; I2 = 75.7%). Five comparative studies of both cohorts totaling 240 patients with dnSCC and 155 patients with IPSCC were included in another meta-analysis. The pooled overall survival hazard ratio was 1.87 (95% CI, 1.24-2.84; I2 = 0%). Conclusions and Relevance: This systematic review and meta-analysis found that patients with dnSCC had almost a 2-fold increased risk of mortality compared with those with IPSCC. Large, multicenter studies are necessary to validate these findings before considering treatment alterations such as de-escalation based on histopathology.

Survival outcomes in sinonasal carcinoma with neuroendocrine differentiation: A NCDB analysis.

BACKGROUND: Sinonasal carcinoma with neuroendocrine differentiation (SCND) is a rare group of tumors with poor prognosis. Treatment and sequence of therapies are still unclear. The goal of this study is to analyze treatment outcomes in SCND using a national database. METHODS: The National Cancer Database was queried for SCND from 2004 to 2014. Patient demographics, tumor characteristics and treatment paradigms were tabulated. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on overall survival (OS). RESULTS: A total of 415 patients were identified. Most patients were male (61.2%), with a median age of 58 years and the most common primary site was the nasal cavity (52.5%). T4 tumors were observed in 67.7% of cases. Unimodality (41.9%) and bimodality (43.9%) therapies were the most common treatment modalities. Radiation therapy was the only treatment administered in 30% of the patients, while 27.2% received definitive chemoradiation (CRT) and 11.6% had surgery with adjuvant CRT. In our Cox-PH model, age (HR = 1.04, p < 0.001), T4 (HR = 2.6, p = 0.004) and N2/N3 (HR = 2.18, p = 0.001) were associated with worse survival. Trimodality (HR = 0.49, p = 0.005) and bimodality (HR = 0.65, p = 0.009) therapies had a better OS compared to unimodality. Patients treated with definitive CRT or surgery with adjuvant CRT had a significant increase in OS (p = 0.01 and 0.002 respectively). CONCLUSION: SCND appears to be best treated using a multimodality approach with definitive CRT or surgery followed by CRT. Neoadjuvant chemotherapy could be helpful in selecting the best treatment strategy.

Geographic and Socioeconomic Factors on Survival in Esthesioneuroblastoma.

OBJECTIVES: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy with little known regarding how regional and socioeconomic differences in the United States alter disease survival. The aim of this study is to explore the geographic difference in clinical features, socioeconomic factors, and survival outcomes of ENB patients. METHODS: ENB cases were extracted from the Surveillance, Epidemiology, and End Results registry from 1975-2016. Patient data were stratified based on geographical location and comparative analyses of socioeconomic features, disease characteristics, and survival patterns were performed. Kaplan-Meier regression analyses were used to estimate disease-specific survival (DSS). RESULTS: A total of 987 patients were identified: 56.4% West, 14.0% South, 12.7% Midwest, and 16.6% East. The West had the highest proportion of patients with Medicaid coverage (P < .001), stage A malignancy (P < .001), and treated with surgery and adjuvant radiotherapy (P < .001). The South had the highest proportion of patients who were Black (P < .001), uninsured (P < .001), and resided in rural areas (P < .001). Five-year DSS patterns were 81.0% (West), 79.8% (East), 67.4% (Midwest), and 72.7% (South) [P = .018]. Ten-year DSS outcomes were 74.0% (West), 73.7% (East), 60.9% (Midwest), and 63.6% (South) [P = .017]. CONCLUSION: In ENB patients, survival disparity exists in the United States based on geographical region. Patients from the West and East exhibit higher survival than those from the South and Midwest. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2162-E2168, 2021.

Comparison of Open and Endoscopic Approaches in the Resection of Esthesioneuroblastoma.

BACKGROUND: Olfactory neuroblastoma, or esthesioneuroblastoma (ENB), is an uncommon sinonasal malignancy arising from olfactory neuroepithelium that is optimally treated with surgical resection. The objective of this study is to determine preoperative predictors of undergoing open versus endoscopic approach for ENB and to investigate significant postoperative survival outcomes between the two surgical approaches. METHODS: The National Cancer Database (NCDB) was queried for cases of ENB histology that were treated surgically from 2010 to 2015. Groups were stratified into open or endoscopic approach cohorts. Patient demographics, tumor characteristics, treatment modality, and 5-year overall survival were compared between the two groups using Chi-Square analysis and Kaplan-Meier survival analysis. Cases were classified as Kadish stage A, B, C, or D based on the "Collaborative Stage-Extension" codes in NCDB. RESULTS: Of 533 patients meeting inclusion criteria, 276 (51.8%) patients underwent open, and 257 (48.2%) patients underwent endoscopic surgical approaches. Patients undergoing endoscopic surgery were more likely to be Kadish stages A and B and less likely to be stages C and D (P = .020). Those undergoing endoscopic approach overall had a shorter mean hospital stay postoperatively (3.8 vs. 7.0 days, P < .001). Endoscopic cases had a greater 5-year overall survival (81.9% vs. 75.6%, P = .030); after multivariate regression, there was a trend toward survival benefit to endoscopic surgery that did not reach clinical significance (HR 0.644, [0.392-1.058], P = .083). CONCLUSION: Although not statistically significant, there is a trend toward increased overall survival with an endoscopic approach in patients undergoing surgery for ENB as compared to an open approach, regardless of Kadish stage. An endoscopic approach is an adequate alternative to an open approach for the surgical treatment of ENB.

Squamous Cell Carcinoma of Nasal Vestibule and Pyramid: Outcomes and Reconstructive Strategies.

OBJECTIVES: Squamous cell carcinoma of nasal vestibule and pyramid is rare, thus classification, treatment protocol, and indications for elective neck treatment are still controversial. Nasal reconstruction is challenging, as well, and prosthesis is still used. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective review of patients surgically treated from 2010 to 2018 in a single Institution. Advanced tumors were further treated with adjuvant irradiation. Reconstruction strategy included grafts, locoregional and free flaps, and was customized on layers removed. RESULTS: Forty-five patients were enrolled. The 5-year overall survival and disease-free survival were 81.9% ± 7.45% and 61.9% ± 9.09%, respectively. Wang's classification, site of origin, extent of surgery and margins status significantly correlated with prognosis and recurrence rate. Regional recurrences occurred in patients affected by advanced tumors who did not receive any form of elective neck treatment. CONCLUSION: Multidisciplinary management and a proper reconstructive algorithm are recommended. Adjuvant irradiation and elective neck treatment should be advocated for advanced stage high-risk patients. LEVEL OF EVIDENCE: 4. Laryngoscope, 131:E1198-E1208, 2021.

Carbon ion radiation therapy for sinonasal malignancies: Promising results from 2282 cases from the real world.

The aim of this study is to compare the effectiveness of carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon-based intensity-modulated radiation therapy (IMRT) in the treatment of sinonasal malignancies. We identified studies through systematic review and divided them into three cohorts (CIRT group/PRT group/IMRT group). Primary outcomes of interest were overall survival (OS) and local control (LC). We pooled the outcomes with meta-analysis and compared the survival difference among groups using Chi2 (χ2 ) test. A representative sample of 2282 patients with sinonasal malignancies (911 in the CIRT group, 599 in the PRT group, and 772 in the IMRT group) from 44 observation studies (7 CIRT, 16 PRT, and 21 IMRT) was included. The pooled 3-year OS, LC, distant metastasis-free survival, and progression-free survival rates were 67.0%, 72.8%, 69.4%, and 52.8%, respectively. Through cross-group analysis, the OS was significantly higher after CIRT (75.1%, 95% CI: 67.1%-83.2%) than PRT (66.2%, 95% CI: 57.7%-74.6%; χ2  = 13.374, P < .0001) or IMRT (63.8%, 95% CI: 55.3%-72.3%; χ2  = 23.814, P < .0001). LC was significantly higher after CIRT (80.2%, 95% CI: 73.9%-86.5%) than PRT (72.9%, 95% CI: 63.7%-82.0%; χ2  = 8.955, P = .003) or IMRT (67.8%, 95% CI: 59.4%-76.2%; χ2  = 30.955, P < .0001). However, no significant difference between PRT and IMRT for OS and LC was observed. CIRT appeared to provide better OS and LC for patients with malignancies of nasal cavity and paranasal sinuses. A prospective randomized clinical trial is needed to confirm the superiority of CIRT in the treatment of sinonasal tumors.

Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastomas: a single center results of 138 patients.

BACKGROUND: The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB). MATERIALS AND METHODS: Between April 1984 and December 2018, 138 patients with non-metastatic ENB were retrospectively analyzed. The treatment modalities mainly included surgery alone (n = 7), radiotherapy alone (n = 33), concurrent chemoradiotherapy (n = 17), surgery combined with current chemoradiotherapy (n = 32), and surgery plus radiotherapy (n = 49). RESULTS: The median follow-up time for the entire cohort was 61 months (range, 4-231 months). The 5-year overall survival (OS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS) rate were 69.6, 78.0 and 73.9%, respectively. Surgery combined with radiotherapy elicited superior survival results, and the combination of surgery and current chemoradiotherapy achieved the best prognoses for all patients, patients with advanced Kadish disease, patients receiving intensity modulated radiation therapy and those with positive surgical margin. Univariate analysis identified orbital invasion and treatment modalities were predictors for OS, LRFFS and DMFS. Lymph node metastasis was associated with OS and DMFS, but not LRFFS. Intracranial invasion, advanced Kadish stage and not receiving concurrent chemotherapy were also predictive of lower OS. Multivariate analyses indicated that lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modalities was independent prognostic factors for OS and LRFFS. CONCLUSION: Orbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. Regarding the treatment modality, the optimal strategy remined surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.

Particle beam radiation therapy for sinonasal malignancies: Single institutional experience at the Shanghai Proton and Heavy Ion Center.

BACKGROUND: Sinonasal malignancies (SNM) include malignant neoplasms of various histologies that originate from the paranasal sinuses or nasal cavity. This study reported the safety and efficacy of particle-beam radiation therapy (PBRT) for the treatment of sinonasal malignancies. METHODS AND MATERIALS: One-hundred-and-eleven patients with nonmetastatic sinonasal malignancies received definitive (82.9%) or salvage (31.5%) PBRT. The majority (85.6%) of patients presented with T3/4 disease, and only 19 (17.1%) had R0 or R1 resection. Seventy (63.1%) patients received carbon-ion radiotherapy (CIRT), 37 received proton radiotherapy (PRT) followed by CIRT boost, and 4 received PRT alone. Prognostic factors were analyzed using Cox regression for univariate and multiple regression. Toxicities were reported using the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS: The median follow-up was 20.2 months for the entire cohort. The 2-year local progression-free survival (LPFS), regional progression-free survival (RPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 83%, 97.2%, 85.9%, 66%, and 82%, respectively. Re-irradiation and large GTV were the significant factors for OS. Melanoma and sarcoma patients had significantly higher distant metastatic rate, and poorer OS and PFS. Late toxicity occurred in 22 (19.8%) patients, but only 4 (3.6%) patients experienced grades 3-4 late toxicity. CONCLUSIONS: Particle-beam radiation therapy results in excellent local-regional control with extremely low serve toxicities for patients with SNM. Sarcoma and melanoma were featured with a greater risk of death from distant dissemination. Patients who underwent re-irradiation had significantly worse OS. PBRT is feasible and safe in the management of SNM.

Aberrant Expression of Prohibitin Is Related to Prognosis of Nasal Extranodal Natural Killer/T Cell Lymphoma, Nasal Type.

INTRODUCTION: Nasal extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) is a high-grade Epstein-Barr virus (EBV)-associated malignancy with poor outcomes. There are few biomarkers for the accurate diagnosis and prognostic prediction of the disease. The aim of this study was to investigate the clinicopathological significance of prohibitin (PHB) expression in nasal ENKTCL. METHODS: The expression level of PHB was detected via immunohistochemical staining in 49 nasal ENKTCL tissues and age- and sex-matched controls of 30 nasal mucosa-reactive lymphoid hyperplasia (NRLH) tissues. The correlations between the PHB expression and clinicopathological features of patients with nasal ENKTCL were evaluated. RESULTS: The results indicated a significantly decreased expression of PHB in nasal ENKTCL tissues compared with in NRLH tissues. Low-level PHB expression was significantly associated with younger age and fever (p = 0.008 and 0.018, respectively). The Kaplan-Meier analysis showed that the cytoplasm expression level of PHB in nasal ENKTCL was inversely related to overall survival (p = 0.046). CONCLUSIONS: PHB may be a potential diagnostic marker and prognostic predictor of nasal ENKTCL.

Treatment and outcome in 12 cases of olfactory neuroblastoma at Mexico´s National Cancer Institute: A retrospective clinical analysis and literature review.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a malignant neoplasm that arises from the upper nasal vault. OBJECTIVE: We present a retrospective case series and clinical analysis of 12 ONB cases. MATERIALS AND METHODS: Patients with ONB treated at Mexico´s National Cancer Institute between 2011 and 2018. RESULTS: The Kadish proportion of B, C, and D stage was 16%, 58%, or 25%, respectively. Hyams Grade 1, 2, or 3 was 25%, 50%, and 25%, respectively. The most common surgical approach was the craniofacial in 5 cases (42%), followed by the transfacial in 4 cases (33%), and the endonasal endoscopic approach in 3 cases (25%). Gross total resection was achieved in 8 patients (67%). Five patients (42%) underwent a second operation due to recurrent/progressive disease. The surgical complication rate was 8.3%. Progression-free survival was 41 months and the mean overall survival was 63.6 months. CONCLUSIONS: Surgical resection followed by radiotherapy, and chemotherapy for metastatic and recurrent disease provides the best outcome in terms of survival and recurrence. To the best of our knowledge, this is the first series of cases reported in Mexico.

ANTECEDENTES: El neuroblastoma olfatorio es una neoplasia maligna que se origina en la bóveda nasal superior. OBJETIVO: Presentar una serie de casos y un análisis clínico retrospectivo. MÉTODO: Pacientes con neuroblastoma olfatorio tratados en el Instituto Nacional de Cancerología, de México, entre 2011 y 2018. RESULTADOS: La proporción de Kadish en las etapas B, C y D fue del 16, el 58 y el 25%, respectivamente. Los grados 1, 2 y 3 de Hyams fueron el 25, el 50 y el 25%, respectivamente. El abordaje quirúrgico más frecuente fue el craneofacial, en cinco casos (42%), seguido del transfacial en cuatro (33%) y del abordaje endoscópico endonasal en tres (25%). La resección total macroscópica se logró en ocho pacientes (67%). Cinco pacientes (42%) se sometieron a una segunda operación debido a enfermedad recurrente o progresiva. La tasa de complicaciones quirúrgicas fue del 8,3%. La sobrevida libre de progresión fue de 41 meses y la supervivencia media global fue de 63,6 meses. CONCLUSIONES: La resección quirúrgica seguida de radioterapia y quimioterapia para la enfermedad metastásica y recurrente proporciona el mejor resultado en términos de supervivencia y recurrencia. Hasta donde sabemos, esta es la primera serie de casos reportados en México.

Cost-effectiveness analysis of proton beam therapy for treatment decision making in paranasal sinus and nasal cavity cancers in China.

BACKGROUND: Cost-effectiveness is a pivotal consideration for clinical decision making of high-tech cancer treatment in developing countries. Intensity-modulated proton radiation therapy (IMPT, the advanced form of proton beam therapy) has been found to improve the prognosis of the patients with paranasal sinus and nasal cavity cancers compared with intensity-modulated photon-radiation therapy (IMRT). However, the cost-effectiveness of IMPT has not yet been fully evaluated. This study aimed at evaluating the cost-effectiveness of IMPT versus IMRT for treatment decision making of paranasal sinus and nasal cavity cancers in Chinese settings. METHODS: A 3-state Markov model was designed for cost-effectiveness analysis. A base case evaluation was performed on a patient of 47-year-old (median age of patients with paranasal sinus and nasal cavity cancers in China). Model robustness was examined by probabilistic sensitivity analysis, Markov cohort analysis and Tornado diagram. Cost-effective scenarios of IMPT were further identified by one-way sensitivity analyses and stratified analyses were performed for different age levels. The outcome measure of the model was the incremental cost-effectiveness ratio (ICER). A strategy was defined as cost-effective if the ICER was below the societal willingness-to-pay (WTP) threshold of China (30,828 US dollars ($) / quality-adjusted life year (QALY)). RESULTS: IMPT was identified as being cost-effective for the base case at the WTP of China, providing an extra 1.65 QALYs at an additional cost of $38,928.7 compared with IMRT, and had an ICER of $23,611.2 / QALY. Of note, cost-effective scenarios of IMPT only existed in the following independent conditions: probability of IMPT eradicating cancer ≥0.867; probability of IMRT eradicating cancer ≤0.764; or cost of IMPT ≤ $52,163.9. Stratified analyses for different age levels demonstrated that IMPT was more cost-effective in younger patients than older patients, and was cost-effective only in patients ≤56-year-old. CONCLUSIONS: Despite initially regarded as bearing high treatment cost, IMPT could still be cost-effective for patients with paranasal sinus and nasal cavity cancers in China. The tumor control superiority of IMPT over IMRT and the patient's age should be the principal considerations for clinical decision of prescribing this new irradiation technique.

Combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase (GDP-ML) for patients with newly diagnosed extranodal natural killer/T cell lymphoma, nasal type: a single arm, single center, prospective phase 2 study.

Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p < 0.001). Patients who achieved CR had significantly better 2-year OS rate compared with non-CR patients (90.8% vs. 24.5%, p < 0.001). The main adverse event was hematologic toxicity. Grade 3/4 neutropenia occurred in 59.1% of patients. These results indicate that GDP-ML is an effective and well-tolerated induction regimen with newly diagnosed ENKL patients. This clinical trial was registered on www.chictr.org.cn (ChiCTR-ONC-12002055).

Comparing Kadish and Modified Dulguerov Staging Systems for Olfactory Neuroblastoma: An Individual Participant Data Meta-analysis.

OBJECTIVE: To compare the Kadish and the modified Dulguerov staging of individual participants to determine the impact of stage and other prognostic factors on disease-free (DFS) and overall survival (OS). DATA SOURCES: Systematic review of EMBASE, MEDLINE, Cochrane Library, and CINAHL databases. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) was followed for this study. Articles including patients with olfactory neuroblastoma (ONB) staged with both Kadish and Dulguerov staging systems were reviewed. The raw data from eligible studies were requested to perform an individual participant data (IPD) meta-analysis. RESULTS: Pooled data from 21 studies representing 399 patients with ONB undergoing treatment with curative intent showed that increasing age, treatment with chemotherapy, and positive or unreported margin status portended worse DFS (P < .05). Increasing stage for both Kadish and Dulguerov staging systems was prognostic for worse DFS and OS (P < .05), with Kadish C representing a heterogeneous group with regard to outcome and corresponding Dulguerov T stage. Using the Akaike information criterion, the Dulguerov staging system had superior performance to the Kadish system for DFS (1088.72 vs 1092.54) and OS (632.71 vs 644.23). CONCLUSION: This study represents the first IPD meta-analysis of ONB directly comparing the outcomes of Kadish and Dulguerov staging systems in patients treated with primary surgery. Both systems correlated with DFS and OS, with superior performance in the Dulguerov system. Furthermore, the Kadish C group represented a heterogeneous group with regard to outcomes after stratification by the Dulguerov system. Dulguerov T4 patients had the worst outcome, with most being approached with open resection.

Local and disease control for nasal melanoma treated with radiation and concomitant anti-programmed death 1 antibody.

Mucosal melanoma of the nasal cavity is a rare disease that has been consistently associated with poor outcome. While complete surgical excision offers the only prospect of a cure, it is associated with a high risk of surgical morbidity due to the challenging anatomical location, and most patients still develop incurable metastatic disease. The efficacy of immunotherapy on mucosal melanoma is lower in comparison with cutaneous melanoma, and mucosal melanoma rarely has BRAF mutations. Although preclinical data have shown that combination treatment with immune checkpoint inhibitors and radiotherapy (RT) improve the response, there have been few reports on the combination of RT and anti-programmed death 1 therapy for mucosal melanoma of the nasal cavity. We retrospectively investigated 10 cases of mucosal melanoma of the nasal cavity in which combined treatment was applied. The local control (LC) rate of the primary lesion and regional lymph nodes was favorably 100%. On the other hand, the median progression-free survival (PFS) time was 29.6 weeks (range, 2-82). The 6-month PFS rate was 60%. Although severe mucositis occurred in one patient, the incidence of treatment-related adverse events was not significantly increased. RT with anti-programmed death 1 antibody therapy for mucosal melanoma of the nasal cavity was tolerable and had the potential to improve LC and PFS.