The Role of Elective Nodal Irradiation in Treating Clinically Node-Negative Sinonasal Squamous Cell Carcinoma.

PURPOSE: This study aims to examine the role of elective nodal irradiation (ENI) in clinically node-negative (cN0) sinonasal squamous cell carcinoma (SNSCC) and to define the optimal radiation fields for ENI. METHODS AND MATERIALS: We retrospectively reviewed 368 cN0 SNSCC patients treated between 2009 and 2021. The study evaluated the impact of ENI on overall survival (OS), progression-free survival (PFS), regional-failure-free survival (RFS), and distant metastasis-free survival (DMFS), along with the coverage areas of ENI. RESULTS: The majority of patients underwent surgery (n=316, 85.9%), with 75% (n=276) having tumors in the maxillary sinus or nasal cavity and 67.7% (n=249) presenting with T4 disease. Additionally, 32.3% (n=119) of the tumors were poorly differentiated. The 5-year OS, PFS, RFS, and DMFS rates were 59.3%, 54.0%, 57.6%, and 58.8%, respectively. ENI was performed in 217 patients (59%), with sixteen experiencing neck relapse during follow-up. While ENI did not enhance survival rates, it significantly reduced the overall regional-failure rate (7.9% vs. 1.8%, χ2 =7.98, p<0.01) and the cumulative incidence of regional failure (p=0.045). Additionally, the subgroups with maxillary sinus origin (2.33% vs. 13.51%, p=0.025), T4 stage (1.80% vs. 8.54%, p=0.028), and poor differentiation (2.44% vs. 13.51%, p=0.029) had higher cumulative incidences of regional failure in patients without ENI. No significant difference was observed in survival and regional failure rates between patients treated with ENI to levels Ib and II with or without level III, as well as between cN0 patients with non-midline crossing lesions receiving unilateral or bilateral ENI. CONCLUSIONS: Despite no survival benefit, ENI significantly decreases the regional failure rate in cN0 SNSCC patients. For primary lesions not crossing the midline, ipsilateral ENI targeting levels Ib and II proves to be an effective strategy.

Personalized treatment for patients with lacrimal sac squamous cell carcinoma.

OBJECTIVE: Lacrimal sac squamous cell carcinoma (LSSCC) is a rare and poor prognosis malignancy. We aimed to investigate the predictive factors for prognosis and to discuss the optimal treatment mode. METHODS: This retrospective study comprised 84 patients with LSSCC who accepted multidisciplinary treatment. We analyzed the potential prognostic factors and the efficiency of different treatment modes in univariate and multivariate analyses. RESULTS: The 5-year overall survival (OS), progression-free survival (PFS), regional failure-free survival (RFS), and distant metastasis-free survival (DMFS) rates for the entire cohort were 83.7%, 76.3%, 77.2%, and 83.7%, respectively. On univariate analysis, orbital bone erosion, lymph node metastasis, and advanced clinical stage were poor prognostic factors. Multivariate Cox regression analysis showed that orbital bone erosion was a uniquely poor predictor for OS; orbital bone erosion, positive cervical lymph nodes, and old age were poor predictors for PFS. Chemotherapy significantly improved the 5-year OS (90.4% vs. 69.6%, p = 0.03), PFS (82.1% vs. 63.6%, p = 0.036), and DMFS (90.4% vs. 69.6%, p = 0.013), except for RFS (82.5% vs. 65.6%, p = 0.15). Surgery did not improve the 5-year OS (85.6% vs. 79.3%, p = 0.062), PFS (76.0% vs. 76.2%, p = 0.41), RFS (76.1% vs. 79.5%, p = 0.54), and DMFS (85.6% vs. 79.5%, p = 0.096). However, the pre-operative radiotherapy conferred a slightly better OS (p = 0.13) and DMFS (p = 0.16) than post-operative radiotherapy and definitive radiotherapy, but without statistical significance. CONCLUSIONS: Orbital bone erosion and lymph node metastasis were poor prognostic factors in LSSCC. Chemoradiotherapy was vital and effective. Although surgery did not improve survival, multidisciplinary treatment, including surgery, was recommended for LSSCC.

Could a low-dose definitive radiation therapy be the optimal treatment for choroidal hemangioma?

PURPOSE: To determine the efficacy of low-dose intensity-modulated radiation therapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) in the treatment of symptomatic choroidal hemangioma (CH). MATERIALS AND METHODS: Fifty-three consecutive patients with CH were retrospectively reviewed. All the patients underwent IMRT/VMAT as a unique treatment. Resolution of subretinal fluid (SRF), improvement of best-corrected visual acuity (BCVA), and reduction in tumor thickness were compared before and after radiotherapy. RESULTS: After definitive radiotherapy, 100 % of SRF and 76.7 % of exudative retinal detachment were resolved. 56.6 % of BCVA improvement in more than two lines was observed. The mean best-corrected visual acuity was 20/280 (range, 20/1200-20/40) at diagnosis and 20/100 (range, 20/1200-20/20) after treatment. The mean tumor thickness decreased significantly from 3.8 mm initially to 1.2 mm after treatment (p < 0.01). 66.0 % of patients were delivered with 21.6 Gy (range, 21.6-42 Gy), 84.9 % of fractional dose was 1.8 Gy (range, 1.8-2 Gy). No radiation-induced keratitis, retinopathy, or optic neuropathy were observed. Initial vision (p = 0.042), duration time of vision (p = 0.004), and tumor thickness (p = 0.049) were prognostic factors for vision recovery. CONCLUSION: Low-dose IMRT/VMAT could effectively induce involution of the CH, with reduction of subretinal fluid and relief of damage to the neurosensory retina, which is an effective treatment mode for CH.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

PURPOSE: In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). METHODS: 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. RESULTS:  Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of 61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). CONCLUSIONS: The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

The treatment efficacy of radiotherapy for optic nerve sheath meningioma.

OBJECTIVES: Optic nerve sheath meningioma (ONSM) is a rare benign tumour that accounts for approximately 2% of all orbital tumours. Radiotherapy has gradually become an important treatment for ONSM because of its good effect in preserving or improving vision. We aimed to explore the effect of radiotherapy on tumour control and vision preservation/improvement in patients with ONSM. METHODS: Forty-three patients with primary ONSM treated in our institution from 2015 to 2021 were enrolled. The irradiation dose was from 50.4 to 54 Gy with 28-30 fractions. We evaluated the tumour volume on MRI or CT, and visual acuity before and after the radiotherapy. RESULTS: Thirty-four patients (79%) experienced a vision decrease at diagnosis. The mean duration of follow-up was 54.1 months (ranges: 18-93, median: 56). Among 25 patients who had tumour evaluation using MRI, 16 patients (37.2%) showed stable tumours, 7 patients (16.3%) had tumour shrinkage, but 2 patients (4.7%) experienced tumour progression. Among the 39 patients performing vision acuity evaluation, 16 patients (37.2%) had vision improvement or recovery. 16 of the 23 patients without vision improvement demonstrated severe visual loss at diagnosis. Two patients had evidence of tumour progression during the follow-up. Additionally, 4 (10.2%) patients had dry eyes, 7 (17.9%) patients experienced watery eyes, and 3 (7.7%) patients had eye swelling. Patients with vision loss for more than 12 months had a lower possibility of vision recovery than those with vision loss for less than 12 months. CONCLUSIONS: Radiotherapy such as IMRT, VMAT, and 3D-CRT plays an important role in the treatment of ONSM. The probability of vision recovery is lower in patients with severe vision loss at diagnosis or the duration of vision loss is more than 12 months.

Surgery for adult head and neck rhabdomyosarcoma: A retrospective report from one institution.

KEY POINTS: Surgery in adults with head and neck rhabdomyosarcoma does not improve survival rates. Surgery should be performed deliberately and focused on the timing of combined treatment modality. Adult head and neck rhabdomyosarcoma benefits from salvage surgery following chemoradiotherapy.

Immunohistochemical p16 expression in the prognosis of patients with sinonasal squamous cell carcinoma.

In sinonasal squamous cell carcinoma (SNSCC), the prognostic relevance of p16INK4a (p16) expression has been reported rarely. This study aims to examine the immunohistochemical expression of p16 and investigate the possibility of p16 as a prognostic factor for SNSCC. The medical records of 173 individuals with SNSCC between 2010 and 2022 were retrospectively reviewed. The researchers examined patients' demographics, p16 status, staging, tumor histological subtypes, treatment details, recurrence, metastasis, and survival outcomes. p16 was found in 22.0% (38/173) of SNSCC patients, and there was no difference between inverted papilloma-SNSCC (19.6%) and de novo SNSCC (23.0%). p16 status did not correlate with all the cases' age, gender, clinical stage, or therapy features. p16-positive patients had a considerably superior 5-year overall survival (OS) rate (80.7% vs. 57.5%, p=0.039) and a slight tendency in progression-free survival (PFS) rate (68.1% vs. 52.0%, p=0.15), except in stage T4b cases. In maxillary sinus lesions, p16-positive SNSCC had a better 5-year OS (87.4% vs. 49.2%, p=0.03) rate and PFS (79.1% vs. 40.7%, p=0.01) rate than p16-negative SNSCC. Among patients without skull base involvement (82.9% vs. 57.7%, p=0.037) or orbital invasion (86.9% vs. 57.3%, p=0.02), p16-positive SNSCC confers benefits in OS rates more than p16-negative SNSCC. Immunohistochemical p16 expression may be a predictive predictor in individuals with maxillary sinus SCC, non-T4b stage, without skull base involvement, and without orbital invasion.

Metal artifacts reduction in kV-CT images with polymetallic dentures and complex metals based on MV-CBCT images in radiotherapy.

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation.

Definitive-intent (chemo)radiotherapy for sinonasal undifferentiated carcinoma.

OBJECTIVE: The current study aimed to investigate the value of definitive-intent (chemo)radiotherapy in treating sinonasal undifferentiated carcinoma (SNUC) in a single institution. METHODS: The medical records of 21 patients with SNUC treated with definitive-intent (chemo)radiotherapy between 2011 and 2021 in one single institution were retrospectively reviewed. We analyzed the treatment efficiency and long-term survivals. RESULTS: A total of 21 patients were included in this cohort, 12 patients presented with T4 stage at diagnosis, and 6 in T1/T2, 3 in T3 stage. Nine patients (42.9%, 9/21) showed cervical lymph node metastases. All the patients were scheduled to receive definitive (chemo)radiotherapy and five patients had been performed surgery for residual tumor after (chemo)radiotherapy. 66.7% (14/21) of patients had a complete response after the completion of treatment, 23.8% (5/21) of partial response, one of stable disease, and one of progressed disease. The 3-year overall survival of the entire group were 86.2%, and the 3-year progress-free survival were 66.3%, respectively. 52.4% of the patients (11/21) presented orbit invasion, compared with patients without orbit invasion, the patients who had orbit invasion were not found to have significantly poor 3-year overall survival (87.5% vs 83.3%, p = 0.38) and 3-year progression-free survival (75.0% vs 55.3%, p = 0.59). CONCLUSION: Definitive-intent (chemo)radiotherapy could be the preferred treatment for patients with advanced SNUC, and salvage surgery should be performed for the lesions showing stable disease, progressed disease, or residual tumor. ADVANCES IN KNOWLEDGE: The value of definitive chemoradiotherapy in treating sinonasal undifferentiated carcinoma.

A preliminary analysis of prognostic genes in advanced laryngeal squamous cell carcinoma patients with postoperative radiotherapy.

Advanced laryngeal squamous cell carcinoma (LSCC) has a high mortality rate, and the prognosis is poor. However, the underlying molecular biological mechanisms bringing about the development and progression of advanced LSCC are not entirely clarified. This study aimed to find out the potential biomarkers to predict the prognosis in advanced LSCC patients who had undergone postoperative radiotherapy alone. The next-generation sequencing of RNA was performed to detect the mRNAs expression profiling in 10 advanced LSCC samples, comprised of 5 samples from LSCC patients with favorable outcome and 5 samples from paired patients with poor outcome. Then bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to find out functional core genes that were significantly different between the two groups. 1630 differentially expressed genes (DEGs) were confirmed to have significant differences between the two groups. 53 GO terms and 19 pathways which were closely related to the DEGs were identified. Finally, 52 intersection DEGs which were both related to the top three GO terms and pathways were identified. The expression of several core genes was confirmed with RT-qPCR in tissues from another 75 patients. RT-qPCR confirmed that the genes of c-JUN, LYN, PIK3R2, and TNFAIP3 were significantly differentially expressed between the two groups, which was in accordance with the RNA sequencing data. The DEGs identified above may be potential prognostic markers for advanced LSCC patients with postoperative radiotherapy, and may provide essential guidance for following-up.

Treatment for SMARCB1 (INI-1) deficient sinonasal tumor: a single-institution study.

Currently, less than 200 cases of SMARCB1-deficient sinus cancer (SDSC) have been documented. Little information is available about the best treatment options or prognosis for SDSC. From September 2016 to November 2022, the medical records of 22 people with SDSC were evaluated retrospectively. Patient demographics, staging, pathology findings, treatment details, recurrence, metastasis, and survival outcomes were all investigated by the researchers. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort were 89.8%, 84.2%, and 45.1%, respectively, as were the 1-, 2-, and 3-year progression-free survival (PFS) rates of 81.8%, 63.8%, and 31.9%. After induction chemotherapy, 66.7% (10/15) of patients exhibited decreased tumor volume. Patients who accepted chemoradiotherapy had a better 2-year OS (100% vs. 72.7%, p=0.048) than those who accepted surgery as a preference. However, there is no difference in 2-year PFS between the two groups (53.0% vs. 75.8%, p=0.59). Patients with progressed or stable disease after induction chemotherapy had a higher risk of developing local recurrence (p=0.007); they also showed poor 2-year PFS (40.0% vs. 82.1%, p=0.019). SDSC had a poor 3-year OS, with a PFS of less than 50%. For locally advanced SDSC, chemoradiotherapy might be managed before surgery, especially in patients who benefit from induction chemotherapy.

The prognostic value of S-100 protein and Ki-67 index in olfactory neuroblastoma.

OBJECTIVE: To evaluate the prognostic value of S-100 protein and Ki-67 labeling index in olfactory neuroblastomas. METHODS: A retrospective study was conducted on a cohort of 85 patients with olfactory neuroblastomas. The immunohistochemical expression of S-100 and Ki-67 was assessed, and the predictive value of S-100 and Ki-67 was further evaluated. The optimal cutoff value of Ki-67 labeling index was determined using time-dependent receiver operating characteristic curve analysis. Overall survival and progression-free survival were assessed using the Kaplan-Meier method. RESULTS: A cut-off Ki-67 labeling index value of 67.5% was determined for prognosis in patients with olfactory neuroblastomas. There was a significant correlation between Ki-67 expression and cervical lymph node metastasis (P = 0.049). Compared with S-100 (+), S-100 (-) was associated with a higher rate of lymph node metastasis and a higher level of Ki-67 (P = 0.007, < 0.001, respectively), as well as an advanced Kadish stage (P = 0.037). Survival analyses showed that patients with S-100 (+) had better 5-year overall survival than those with S-100 (-) (P = 0.028), and patients with both S-100 (+) and Ki-67 (<67.5%) had superior 5-year overall survival compared with all the other patients (P = 0.0225). CONCLUSION: Our findings suggest that S-100 combined with Ki-67 labeling index are reliable prognostic factors in patients with olfactory neuroblastomas.

Mucosa-associated lymphoid tissue of nasopharynx: A case report and literature review.

Nasopharyngeal MALT lymphoma is a rare disease, with limited cases reported in the literature. To the best of our knowledge, there is no research detailing the treatment of nasopharyngeal MALT lymphoma. In this present paper, we report an unusual case of a 70-year-old female patient with nasopharyngeal MALT lymphoma. The patient was treated with radiotherapy alone. The detailed radiation therapy of the treatment was demonstrated. The patient is free of locally recurrent or distant disease at two years. Radiotherapy alone can be a helpful treatment for MALT lymphoma confined to the nasopharyngeal cavity.

Is prophylactic neck irradiation indicated for patients with cN0 adenoid cystic carcinoma of the paranasal sinuses?

PURPOSE: To study the prevalence of nodal metastases in sinonasal adenoid cystic carcinoma (SNACC) and to evaluate whether prophylactic neck irradiation (PNI) should be performed in patients with clinical N0 (cN0) disease. PATIENTS AND METHODS: Between April 1992 and November 2020, 166 patients with SNACC who had undergone radiotherapy at our department were retrospectively analyzed. The median follow-up time was 71.3 months. RESULTS: Among 166 cases of SNACC, a total of 13 (7.8%) had retropharyngeal or cervical nodal metastasis and 93% (12/13) cases occurred in patients with advanced T stage (T3-T4). Levels VIIa, Ib, and IIa were the most common sites of initial nodal involvement. Only 1.2% (2/166) of patients presented late neck recurrence. Lymph node metastasis independently predicted a poor progression-free survival (PFS) (P = 0.017) but had no impact on overall survival (OS) (P = 0.38). PNI was performed on 36% (55/153) of cN0 patients. The OS (P = 0.42), PFS (P = 0.59), nodal recurrence-free survival (NRFS) (P = 0.46) and distant metastasis-free survival (DMFS) (P = 0.63) rates showed no significant difference between cases with and without PNI. Furthermore, cN0 patients with T4b (P = 0.53; P = 0.61), tumor origin from maxillary sinus (P = 0.55; P = 0.53) or nasopharynx involvement (P = 0.56; P = 0.60) showed no extended OS or PFS associated with PNI. CONCLUSIONS: Regardless of the T stage or the site of origin, prophylactic neck irradiation (PNI) for cN0 patients did not provide any benefit on OS and PFS, suggesting that its application on such patients is not warranted unless there is clinical suspicion.

Targeting HIF-1α/NOTCH1 pathway eliminates CD44+ cancer stem-like cell phenotypes, malignancy, and resistance to therapy in head and neck squamous cell carcinoma.

Poor prognosis of head and neck squamous cell carcinomas (HNSCCs) results from resistance to chemotherapy and radiotherapy. To uncover the drivers of HNSCC resistance, including stemness and hypoxia, in this study, we compared the gene expression between CD44+ and CD44- HNSCC cells and assessed the correlation of CD44 and hypoxia-inducible factor 1α (HIF-1α) expression with mouse features and outcomes of patients with HNSCC. We combined the knockdown or activation of HIF-1α with in vitro and in vivo assays to evaluate effects on stemness and resistance of HNSCC cells. Analysis of clinical data showed that activation of HIF-1α in CD44+ patients with HNSCC was correlated with worse prognosis. Functional assays showed that HIF-1α promoted stemness, resistance, and epithelial-mesenchymal transition in HNSCC CD44+ cells. HIF-1α activated NOTCH1 signaling in HNSCC stem-like cells characterized by CD44 expression. Moreover, inhibition of these signaling proteins using shRNA or Evofosfamide (Evo) development for cancer treatment, reversed chemoresistance in vitro and in vivo. Taken together, our results indicated that targeting HIF-1α attenuated NOTCH1-induced stemness, which regulates responses to chemotherapy or radiotherapy and malignancy in CD44+ HNSCCs. HIF-1α/NOTCH1 signaling may represent a target for HNSCC treatment.

The role of 18F-FDG PET/CT in diagnosis and treatment evaluation for ocular adnexal mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. RESULTS: The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. CONCLUSION: 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. ADVANCES IN KNOWLEDGE: The value of 18F-FDG PET/CT for patients with OAML.

Induction chemotherapy plus nimotuzumab followed by concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma.

INTRODUCTION: This study investigated the best mode for the application of nimotuzumab (Nimo) in combination with chemoradiotherapy to treat nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS: Data were prospectively collected from 168 patients with NPC from September 2009 to February 2014. One hundred twelve patients received 2-3 cycles of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT), and 56 patients with well-matched propensity scores received IC + CCRT + Nimo. Patients were divided into 3 subgroups according to the application schedule of Nimo: group A, IC + CCRT; group B: IC (combined with Nimo) + CCRT; and group C: IC + CCRT (combined with Nimo). The 5-year overall survival (OS) and progression-free survival (PFS) and adverse events were investigated. RESULTS: With a median follow-up of 61.4 months (range: 1.7-96.5 months), the 5-year OS and PFS for group A vs. groups B + C were 74.8 ±4.1% versus 87.0 ±4.6% (p = 0.043) and 72.7 ±4.3% vs. 83.1 ± 5.1% (p = 0.243), respectively. The 5-year OS of group B was significantly improved over that of group A (93.0 ±4.8% vs. 74.8 ±4.1%, p = 0.038); however, there was no benefit to the 5-year PFS (89.3 ±5.9% vs. 72.7 ±4.3%, p = 0.144). The 5-year OS and PFS for group C were 80.4 ±7.9% and 76.4 ±8.5%, respectively, and there was no statistically significant difference from group A (p = 0.257 and p = 0.611, respectively). No significant increase in toxicities was observed with the addition of Nimo. CONCLUSIONS: Nimo administered with chemoradiotherapy is effective for NPC. Nimo concurrent with IC followed by CCRT could be the optimal mode of sequential treatment.

TERT Promoter Mutations Are Enriched in Oral Cavity Cancers and Associated With Locoregional Recurrence.

Telomerase reverse transcriptase (TERT) promoter mutations are prognostic in many cancers and have been observed in human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). However, the role of TERT promoter mutations in HPV-negative HNSCCs remains poorly understood in these cancers, which have increased risk for locoregional failure (LRF). PATIENTS AND METHODS: We retrospectively identified patients who were diagnosed with HNSCC between July 1, 2004, and October 12, 2017, at Memorial Sloan Kettering Cancer Center and whose tumors underwent next-generation sequencing using the MSK-IMPACT panel. Patients with HPV-positive oropharyngeal squamous cell carcinoma (SCC) were excluded. Cumulative incidence of LRF, patterns of failure, and overall survival were measured. RESULTS: We identified 117 patients with SCC of the oral cavity (OSCC), larynx, hypopharynx, or HPV-negative oropharynx whose tumors underwent next-generation sequencing. Sequencing was performed on 95 tumors that were obtained after recurrence and 22 that were obtained before recurrence. TERT promoter mutations were enriched in OSCC compared with laryngopharyngeal cancers (81.1% v 7.0%; P < .001), which was the largest genetic difference between these anatomic disease subsites. TERT promoter mutations were associated with LRF in OSCCs (Gray's test, P < .001) and in the overall cohort (Gray's test, P < .001). On multivariate analysis, TERT promoter mutations were associated with an increased risk for LRF (subdistribution hazard ratio, 2.82; 95% CI, 1.47 to 5.42; P = .0019), independent of oral cavity primary site and TP53 mutation status. CONCLUSION: TERT promoter status is associated with the cumulative incidence of LRF and patterns of failure. TERT promoter mutations may define a subset of OSCCs with unique pathogenesis that is associated with an increased risk of LRF. Validation in prospective cohorts is warranted.

The Treatment Outcomes of Olfactory Neuroblastoma Patients With Frontal Lobe Invasion.

BACKGROUND: To investigate whether frontal lobe invasion (FLI) was an unfavorable prognostic factor in patients with olfactory neuroblastoma (ONB), and to explore the optimal treatment strategy for ONB patients with FLI. METHODS: Some 37 patients with FLI were retrospectively studied, and 74 well-matched patients without FLI were enrolled as the control group. The long-term survivals were compared between the two groups. RESULTS: No significant differences were found between the two groups in overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS) (all p >0.05). Multivariate analyses showed that FLI wasn't an independent predictor for OS (HR = 1.100, 95% CI = 0.437-2.772, p = 0.840). Among the 37 patients with FLI, patients who received surgery combined with chemo-/radiotherapy showed better OS (89.4% vs. 53.6%, p = 0.001) and PFS (87.8% vs. 53.6%, p = 0.001) compared with those who didn't undergo surgery. CONCLUSIONS: FLI wasn't a poor prognostic factor for ONB patients. Endoscopic resection combined with radiotherapy was an effective therapeutic method for ONB patients with FLI.

Pathogenic ATM Mutations in Cancer and a Genetic Basis for Radiotherapeutic Efficacy.

BACKGROUND: Radiation therapy is one of the most commonly used cancer therapeutics but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common event in a wide variety of cancers, but its clinical actionability remains obscure. METHODS: We analyzed 20 107 consecutively treated advanced cancer patients who underwent targeted genomic sequencing as part of an institutional genomic profiling initiative and identified 1085 harboring a somatic or germline ATM mutation, including 357 who received radiotherapy (RT). Outcomes of irradiated tumors harboring ATM loss-of-function (LoF) mutations were compared with those harboring variants of unknown significance. All statistical tests were 2-sided. RESULTS: Among 357 pan-cancer patients who received 727 courses of RT, genetic inactivation of ATM was associated with improved radiotherapeutic efficacy. The 2-year cumulative incidence of irradiated tumor progression was 13.2% vs 27.5% for tumors harboring an ATM LoF vs variant of unknown significance allele, respectively (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.34 to 0.77, P = .001). The greatest clinical benefit was seen in tumors harboring biallelic ATM inactivation (HR = 0.19, 95% CI = 0.06 to 0.60, P = .005), with statistically significant benefit also observed in tumors with monoallelic ATM inactivation (HR = 0.57, 95% CI = 0.35 to 0.92, P = .02). Notably, ATM LoF was highly predictive of outcome in TP53 wild-type tumors but not among TP53-mutant tumors. CONCLUSIONS: We demonstrate that somatic ATM inactivation is associated with markedly improved tumor control following RT. The identification of a radio-sensitive tumor phenotype across multiple cancer types offers potential clinical opportunities for genomically guided RT.