Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial.

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

[Retracted] Knockdown of circ_0001883 may inhibit epithelial­mesenchymal transition in laryngeal squamous cell carcinoma via the miR­125­5p/PI3K/AKT axis.

[This retracts the article DOI: 10.3892/etm.2021.10440.].

Efficacy and safety of Huachansu combined with adjuvant chemotherapy in resected colorectal cancer patients: a prospective, open-label, randomized phase II study.

Although some studies in China have suggested Huachansu (HCS) combined with chemotherapy is effective in the treatment of various cancers, there are few studies on colorectal cancer (CRC), especially in postoperative adjuvant chemotherapy. The aim of this study was to test the hypothesis that HCS combined with adjuvant chemotherapy would improve survival probability in resected CRC patients. This was a prospective, open-label, randomized phase II study. Patients with stage III or high-risk stage II resected CRC were randomly assigned to the chemotherapy and HCS + chemotherapy groups. The Chemotherapy group was treated with the FOLFOX regimen for ≥ 6 cycles or the CAPEOX regimen for ≥ 4 cycles. The HCS + chemotherapy group was treated with HCS on the basis of the chemotherapy group. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 3-year overall survival (OS) and toxicity. A total of 250 patients were included in this study (126 chemotherapy, 124 HCS + chemotherapy). There were significant differences in 3-year DFS between the two groups (median 28.7 vs. 31.6 months, respectively; P = 0.027), but no significant differences in 3-year OS between the two groups (median 32.7 vs. 34 months, respectively; P = 0.146). No patients experienced grade four adverse events, and the rates of leukopenia, neutropenia, and diarrhea in the HCS + chemotherapy group were lower than that those in the chemotherapy group. HCS combined with adjuvant chemotherapy after radical resection for patients with stage III or high-risk stage II CRC was demonstrated to be an effective and feasible treatment.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

Abstract Objectives The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. Results Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T = 3.425) and right calcarine sulcus (T = 3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. Conclusions The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up.

OBJECTIVES: The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. METHODS: 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. RESULTS: Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = -8.797), left insular lobe (T = -7.96), and the right insular lobe (T = -6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = -2.366), left olfactory bulb (T = -2.52), left Rolandic operculum (T = -2.431), and right olfactory bulb (T = -3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. CONCLUSIONS: The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma.

BACKGROUND: For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed. METHODS: Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3). RESULTS: Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302). CONCLUSIONS: Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.

Induction chemotherapy of modified docetaxel, cisplatin, 5-fluorouracil for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma.

BACKGROUND: Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC). METHODS: One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019. RESULTS: In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p = 0.03). There was no difference in overall survival and the adverse events were tolerable. CONCLUSIONS: The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.

Elevation of miR-125b-5p is related to improved prognosis in laryngeal squamous cell carcinoma and inhibits the malignancy and glycometabolic disorder by targeting MAP3K9.

Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck cancer, with a poor prognosis. As we know, microRNAs (miRNAs) play a vital role in the initiation and development of various cancers including LSCC. In this study, we explored the role of miR-125b-5p and its downstream regulatory pathway in LSCC. Our data demonstrated that miR-125b-5p expression was significantly downregulated in LSCC tissues and cells. LSCC patients with high expression of miR-125b-5p had higher overall survival (OS) and were closely related to the clinical stage. Overexpression of miR-125b-5p impaired viability and glycolysis, and facilitated apoptosis in LSCC cells. And miR-125b-5p silencing had the opposite effects. Bioinformatics website predicted that MAP3K9 was one of the potential target genes of miR-125b-5p. Cell experiments demonstrated that miR-125b-5p repressed the MAP3K9 levels by directly targeting MAP3K9. Additionally, the negative correlation between miR-125b-5p and MAP3K9 was validated in LSCC tissues. Overexpression of MAP3K9 attenuated the inhibitory effect of miR-125b-5p on viability and glycolysis, and the pro-apoptosis effect of miR-125b-5p in LSCC cells. Furthermore, in vivo experiments demonstrated that tumor growth was hampered in AMC-HN-8 cells transfected with miR-125b-5p mimic. In contrast, the knockdown of miR-125b-5p reduced tumor growth in vivo. Meanwhile, the in vivo immunohistochemistry and TUNEL assays suggested that the miR-125b-5p overexpression restrained cell proliferation and promoted apoptosis via targeting MAP3K9. Overall, these above results suggested that miR-125b-5p suppressed proliferation and glycolysis, and promoted apoptosis by directly targeting MAP3K9 in LSCC cells. Thus, miR-125b-5p acts as a tumor suppressor miRNA and the miR-125b-5p/MAP3K9 axis may be a promising candidate for LSCC treatment.

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.

Knockdown of circ_0001883 may inhibit epithelial-mesenchymal transition in laryngeal squamous cell carcinoma via the miR-125-5p/PI3K/AKT axis.

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with increasing incidence and poor prognosis. Circular RNAs (circRNAs) are known to modulate tumorigenesis and cancer development that may function through microRNAs (miRs). The aim of the present study was to investigate the functional roles of circ_0001883 in LSCC and the underlying molecular mechanism. The expression of circ_0001883 was upregulated and measured using reverse transcription-quantitative PCR (RT-qPCR) and RNase R. miR-125b-5p expression was downregulated in LSCC tissues and cells as determined using RT-qPCR. Subsequently, knockdown of circ_0001883 inhibited LSCC cell migration, invasion and epithelial-mesenchymal transition (EMT), which were tested by wound healing assays, Transwell assays and western blotting, respectively. Bioinformatics analysis predicted that circ_0001883 was a sponge of miR-125b-5p, which was verified using a dual-luciferase reporter assay. Knockdown of circ_0001883 played a functional role by sponging miR-125b-5p. Additionally, circ_0001883 and miR-125b-5p influenced phosphorylation of PI3K and AKT, detected via western blotting. In an in vivo study, knockdown of circ_0001883 reduced tumor volume and weight in mice, along with enhanced miR-125b-5p and E-cadherin expression levels, and decreased N-cadherin, phosphorylated (p)-PI3K/PI3K and p-AKT/AKT ratios. In conclusion, knockdown of circ_0001883 inhibited cell migration, invasion and EMT of LSCC by sponging miR-125b-5p. This is hypothesized to be via the PI3K/AKT signaling pathway, which suggested that circ_0001883 has potential for LSCC therapy.

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

PURPOSE: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). METHODS AND MATERIALS: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival. RESULTS: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. CONCLUSIONS: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

Radiotherapy versus partial laryngectomy in the management of early glottic cancer with anterior commissure involvement: A propensity score matched study with 256 patients.

OBJECTIVES: The study was intended to compare the outcomes for T1-T2N0M0 glottic squamous cell carcinoma with anterior commissure involvement who had undergone partial laryngectomy (PL) or radiotherapy (RT). MATERIALS AND METHODS: We retrospectively analyzed 256 patients who were treated by RT (n = 70) or PL (n = 186). Patients received prophylactic irradiation of the neck in RT group whereas PL was not associated with lymphadenectomy. Propensity score matching (PSM) was used to eliminate the baseline variations. RESULTS: The average age of the RT group (67 years) was significantly higher than that of the PL (59 years). Local recurrence was noted in 14 patients of the RT group and 22 of the PL. While regional recurrence was noted in only 1 patient of the RT group and 23 of the PL. After PSM, the 5-year overall survival (82.8% vs. 83.9%, p = 0.302), 5-year cancer-specific survival (88.3% vs. 89.7%, p = 0.793), 5-year local relapse-free survival (79.3% vs. 84.5%, p = 0.127) were not significantly different between two groups. However, 5-year regional relapse-free survival in the RT group was significantly better than that in the PL (100% vs. 87.1%, p = 0.014). In the PL group, infection, granuloma, laryngeal stenosis, chylous leakage, and pharyngeal fistula were reported in six, 11, 12, one, and two patients, respectively. CONCLUSIONS: RT resulted in comparable rates of survival, local control, and larynx preservation compared to PL. However, RT was associated with higher regional control rate. The complication rates were extremely low in RT group.

Treatment outcomes after definitive radio(chemo)therapy for 17 lacrimal sac squamous cell carcinoma.

OBJECTIVES: Tumors of the lacrimal sac are rare and life-threatening. Because of their rarity, no extensive clinical data on their management and prognosis exist. We investigated the application of definitive radiation therapy and its outcome in patients with lacrimal sac squamous cell carcinoma (LSSCC). METHODS: We retrospectively studied 17 patients with LSSCC at a single institution between 2003 and 2017. All the patients were treated with definitive radiotherapy, and 11 patients were delivered with cisplatin-based chemotherapy. The patients' clinical records were reviewed for symptoms, pathological types, the volume and dosimetry of the tumors and their adjacent structures, radiation coverage of lymph node drainage areas, treatment outcomes, and complications from definitive radiotherapy. RESULTS: Median follow-up was 38.9 months, and age at diagnosis was 48 years.The 2-year and 5-year overall survival, progression-free survival, locoregional control, and disease metastasis-free survival rates were 94.1 and 84.7%, 88.2 and 73.5%, 93.8%, 94.1, and 78.4%, respectively. A total dose of 6600-7000 cGy was prescribed to the tumor. Levels Ⅰb, Ⅶa, Ⅷ, and Ⅸ were covered with the clinical target volume regardless of lymph involvement. Acute Grade 3 radiation dermatitis occurred in seven patients (17.6%), but no acute Grade 4 or Grade 5 toxicity of any type occurred. Seven (41.2%, 7/17) of the treated eyes had moderated vision impairments; 17.6% (3/17) of patients developed cataracts, and glaucoma and radiation retinopathy were found in 5.9% (1/17) of patients. CONCLUSIONS: Definitive radiotherapy could be a treatment option for those who refuse surgery or have unresectable LSSCC. ADVANCES IN KNOWLEDGE: Radiation alone is a treatment option for LSSCC.

Prevalence of human papillomavirus in sinonasal squamous cell carcinoma with and without association of inverted papilloma in Eastern China.

BACKGROUND: Information on HPV-associated sinonasal squamous cell carcinoma (SNSCC) is very limited in China. The aim of this study was to determine the prevalence of HPV in a large cohort of SNSCC patients in China. METHODS: Clinical records and formalin-fixed and paraffin-embedded tumor specimens from 30 SNSCC patients with associated inverted papilloma (IP-SNSCC) and 84 de novo SNSCC (DN-SNSCC) patients were retrieved between 2010 and 2017. HPV status was determined for each specimen using a combination of p16 immunohistochemistry and GP5+/6+ PCR. RESULTS: Immunohistochemistry for p16 was positive in two IP-SNSCC patients (2/30, 6.7%) and in 16 DN-SNSCC patients (16/84, 19.0%). HPV DNA was detected in six IP-SNSCC patients (6/30, 20%) and in three DN-SNSCC patients (3/84, 3.8%). Expression of p16 was not correlated with the presence of HPV DNA (p = 0.150). Among 18 p16-positive SNSCC patients, only three were HPV DNA-positive. Furthermore, only three of nine HPV DNA-positive tumors exhibited high p16 expression. In IP-SNSCC patients, only one of six HPV DNA-positive tumors exhibited high p16 expression. In DN-SNSCC patients, two of three HPV DNA-positive tumors exhibited high p16 expression. The positive rates for both HPV DNA and p16 in IP-SNSCC patients and DN-SNSCC patients were 3.3 and 2.4%, respectively. CONCLUSIONS: Immunostaining for p16 is not a reliable surrogate marker of HPV status in SNSCC. The presence of HPV is rarely detected in DN-SNSCC patients in Eastern China. IP-SNSCC patients frequently lack of p16 overexpression despite the presence of high-risk HPV DNA.

Prognostic factors and outcomes of multimodality treatment in olfactory neuroblastoma.

OBJECTIVE: The clinical data on olfactory neuroblastomas (ONBs) are scarce owing to their rarity. This study aimed to assess the potential prognostic factors, outcomes, and optimal treatment strategies in patients with ONB. METHODS AND MATERIALS: The data of 217 patients with ONB between 1991 and 2019 were retrospectively reviewed. Long-term survival, potential prognostic factors, and outcomes with combined treatment strategies were analyzed. RESULTS: All patients received radiotherapy (RT); 185 patients underwent surgery, and 139 patients received chemotherapy. The 5-year overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFS), and distant metastasis-free survival (DMFS) of the entire cohort were 80.0%, 79.0%, 79.3%, and 80%, respectively. On univariate analyses, R0/R1 resection, early Kadish stage, negative lymph nodes, absence of orbital invasion, and administration of surgery with RT were found to be favorable factors. Conversely, combined sequential treatment with surgery, RT, and chemotherapy was not associated with survival. Multivariate analysis demonstrated lymph node status, orbital invasion, and the combination of surgery and RT to be independent prognostic factors. CONCLUSIONS: Patients with ONB, who had lymph node metastases, orbital invasion diseases, advanced Kadish stages, R2 resection margins, and received RT alone, had poor outcomes. Combined administration of surgery and RT may be a potentially useful strategy in patients with advanced Kadish stages; the role of chemotherapy in these stages requires further evaluation.

Comparison of outcomes between patients with de-novo sinonasal squamous cell carcinoma vs malignant transformations from inverted papillomas.

BACKGROUND: The survival difference between de-novo sinonasal squamous cell carcinoma (DN-SNSCC) and SCC arising from inverted papillomas (IPs) is unclear. The purpose of this study was to compare the outcomes between DN-SNSCC and IP-transformed SNSCC (IP-SNSCC) patients. METHODS: In this retrospective review, we compared IP-SNSCC and DN-SNSCC cases from the Eye and ENT Hospital of Fudan University from 2010 to 2017. A total of 162 patients (39 IP-SNSCC and 123 DN-SNSCC) were included in our study. Demographics, tumor characteristics, treatment, and clinical outcomes were analyzed. RESULTS: The median follow-up time in all cohorts was 56 (range, 5-109) months. There was no difference in age, sex, smoking history, alcohol consumption, tumor primary site, or disease stage between the IP-SNSCC and DN-SNSCC patients. We also did not find significant differences in overall survival and disease-free survival between IP-SNSCC and DN-SNSCC patients (p = 0.584 and p = 0.238, respectively). The 5-year local failure rate was 52.8% for IP-SNSCC patients, which was significantly higher than for those with DN-SNSCC (31.9%; p = 0.013). The 5-year nodal failure rate was 19.0% for IP-SNSCC patients and 8.5% for DN-SNSCC patients (p = 0.211). The 5-year distant metastasis rate was 8.0% for IP-SNSCC patients and 16.1% for DN-SNSCC patients (p = 0.318). CONCLUSION: IP-SNSCC and DN-SNSCC patients have similar survival outcomes. IP-SNSCC seems to have exhibited a higher local failure rate in our study. We believe that IP-SNSCC is a highly aggressive disease that requires radical treatment. Prophylactic neck treatment should not be omitted in a subset of IP-SNSCC patients.

Management of orbital invasion in sinonasal squamous cell carcinoma: 15 years' experience.

BACKGROUND: This study was intended to review our management strategy for sinonasal squamous cell carcinomas (SNSCCs) with orbital invasion and to explore the role of radiotherapy in orbital preservation. METHODS: We retrospectively analyzed 93 SNSCC patients with orbital invasion who underwent radiotherapy with or without surgery over the past 15 years. The degree of orbital invasion was classified into 3 grades. RESULTS: Eighty-eight patients presented with T4 tumors and 36 had grade III orbital invasion. Seventy-two patients received surgery plus radiation and 67 received platinum-based chemotherapy. The median follow-up for surviving patients was 60 months. Five-year overall survival (OS) for the whole group was 57.4%. The patients treated with surgery plus radiation had a 5-year survival rate of 62.2% and orbital preservation was feasible in 90.3% of cases. Twenty-one patients with SNSCCs that extended into the extraocular muscles or eye globe also underwent orbital preservation. Five-year locoregional relapse-free survival (LRFS) was 69.5% for patients treated with orbital preservation and 57.1% for those treated with orbital exenteration, indicating no statistical difference. Five-year survival, 5-year progression-free survival (PFS), and 5-year distant metastasis-free survival (DMFS) were similar between groups. Grade III orbital invasion was independently associated with shorter OS, LRFS, PFS, and DMFS. CONCLUSION: Orbital invasion in grade III was associated with the worst survival outcomes. Invasion of either the extraocular muscles or eye globe is not a contraindication for eye-sparing surgery. Preoperative chemoradiation continues to offer hope to patients with a strong desire to preserve their eyes.

Neck management in patients with olfactory neuroblastoma.

OBJECTIVE: Optimal neck management in patients with olfactory neuroblastoma (ONB), a rare malignancy, remains uncertain. This study aimed to analyse patterns of cervical lymph node metastases and corresponding clinical outcomes and to investigate the value of elective neck irradiation (ENI) in this population. METHODS AND MATERIALS: This study retrospectively reviewed clinical records, imaging findings, nodal metastasis features and treatment data of 217 patients with ONB treated at our hospital during 1991-2019. Univariate and multivariate analyses were used to assess the influence of cervical lymph node involvement on treatment outcomes. Survival and regional failure rates were compared between patients with or without ENI. RESULTS: Thirty-two patients (14.7%) presented initially with cervical lymph node metastases, most frequently at levels II (10.6%, 23/217) and VIIa (5.5%, 12/217). Patients with and without cervical node metastasis differed significantly in overall (OS) (41.9% vs. 86.1%, p < 0.001), progression-free (PFS) (41.9% vs. 84.8%, p < 0.001), regional failure-free (45.9% vs. 89%, p < 0.001) and distant metastasis-free survival (41.5% vs. 86.1%, p < 0.001). Cervical lymph involvement was an independent factor affecting poor OS (hazard ratio, 0.184, 95% confidence interval, 0.078-0.436, p < 0.001) and PFS (hazard ratio, 0.198, 95% confidence interval, 0.088-0.445, p < 0.001). Moreover, 43.8% patients (95/217) underwent ENI, which significantly reduced the incidence of regional recurrence from 10.7% to 3.2% (χ2 = 4.396, p = 0.036) but did not significantly affect other survival outcomes. Regional failures could be resolved using salvage treatment. CONCLUSIONS: Our findings indicate the importance of systematic therapy for patients with initial cervical lymph node metastases. ENI is not recommended for N0 disease.

Comparative outcome of surgical and nonsurgical therapy for T4bN0M0 sinonasal squamous cell carcinomas.

PURPOSE: Definitive radiotherapy (RT) is recommended by NCCN guidelines for T4b tumors of sinonasal squamous cell carcinomas (SNSCC). However, no multi-institutional clinical studies have proved its advantage over surgery-based modalities. The aim of this study was to assess the survival of T4bN0M0 SNSCC patients who received surgery plus postoperative radiation (S + PORT) compared with those who received RT. METHODS: This study extracted 220 patients from the SEER database from 2004 to 2015. Propensity score matching (PSM) was used to eliminate the baseline variations. RESULTS: In SEER database, 43.6% of patients received S + PORT, and subsequently followed by RT (36.4%). Five-year overall survival (OS) and cancer-specific survival rates (CSS) in S + PORT were 42.5% and 46.9%, respectively, significantly better than for RT (21.7% and 26.7%). Multivariate analysis showed that therapy of RT had higher cancer-specific mortality risk than S + PORT [hazard ratio (HR) 1.578, p = 0.032]. After PSM, 57 pairs of patients were selected. There was still a significant difference noted with regard to 5-year OS or 5-year CSS between patients receiving S + PORT and RT (43% vs 22.5%, p = 0.012; 45.8% vs 27.7%, p = 0.025). The univariate and multivariate analyses of factors predictive of CSS showed that therapy of RT (HR 1.877, p = 0.018) and primary subsite of maxillary sinus (HR 2.629, p = 0.001) were significantly correlated with adverse outcomes. CONCLUSION: Combination of surgery and postoperative radiotherapy may contribute to prolonged survival in T4bN0M0 SNSCC. Invasion of the sites of T4b tumors is not an absolute contraindication for surgery.

Studying the impact of young age on prognosis and treatment in laryngeal squamous cell carcinomas using the SEER database.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) in young patients was reported to be more aggressive and associated with poorer survival than in older patients. However, very few studies contained sufficient cases to permit meaningful statistical analysis. It is still unknown whether less aggressive method like radical radiotherapy (RT) is comparable to total laryngectomy (TL) in survival rate among young patients. METHODS: This study extracted patient data from the surveillance, epidemiology, and end results database from 2004 to 2015. The findings for 304 patients (1.2%) below the age of 40 were compared with those for 24,827 patients (98.8%) aged 40 or older. RESULTS: The younger cohorts contained a higher proportion of female patients (33.6% vs. 19.1%, respectively), had more cases of glottic involvement (64.5% vs. 53.1%), and were less likely to have distant metastasis (0.7% vs.3.2%). A total of 5-year overall survival and cancer-specific survival rates (CSS) in the younger patients were 86.3% and 88.8%, respectively, significantly better than for older patients (53.8% and 67.6%). Significant differences were still observed when stratified for tumor stage (stage I-IV). The negative independent prognostic factors in younger patients were advanced tumor stage, degree of nodal involvement, and status of distant metastasis. Treatment with surgery and/or RT all produced excellent outcomes in stage I-IV diseases, and radical RT resulted in survival rates equal to those for TL in locally advanced LSCC among young patients (5-year CSS: 90% vs. 91.5%, p = 0.99). CONCLUSION: LSCC is less aggressive and has significantly better survival in younger patients. For younger patients, advanced nodal involvement is the most important independent prognostic factor, and larynx preservation is comparable to TL in survival rate.