Impact of Radiation Dose on Treatment of Maxillary Cancer With Superselective Intra-arterial Cisplatin With Radiotherapy.

BACKGROUND/AIM: Maxillary sinus cancer is a relatively rare disease, and treatment is still evolving. We compared the efficacy of superselective intra-arterial infusion of high-dose cisplatin (CDDP) with concomitant radiotherapy (RADPLAT) using three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) and analyzed the relationship between the total radiation dose and the treatment outcome in localized maxillary sinus cancer. PATIENTS AND METHODS: We reviewed the cases of 58 patients with localized maxillary sinus cancer treated with RADPLAT at our institution from March 2004 to November 2020. These 58 patients included 34 who received 3DCRT and 24 who received IMRT. RESULTS: The median follow-up period was 38.4 months. The median prescribed dose to the local lesion was 66 Gy in the 3DCRT group and 70 Gy in the IMRT group. CDDP (100-120 mg/m2) was administered once a week for a median of 6 cycles. The 5-year local control rate and overall survival rate were 69.9% and 72.2%, respectively. The patients treated with 70 Gy had a significantly higher local control rate (87.7%) than those treated with 60 Gy or less (41.0%) (p=0.011). No late grade 3 or higher eye disorders except for cataracts developed in the IMRT group, while grade 4 eye disorders occurred in four patients receiving 3DCRT. CONCLUSION: IMRT can escalate radiation dose safely with acceptable toxicities. The total dose may have an impact on the local control rate in RADPLAT.

A case report of sinusoidal diffuse large B-cell lymphoma in a STK4 deficient patient.

INTRODUCTION: Primary immunodeficiency diseases (PIDs), a rare group of gene defects with different manifestations, are at great risk of malignancy. The incidence of diffuse large B-cell lymphoma in the sinusoidal tract is quite rare with nasal congestion, stuffiness, and pain in maxillary sinus manifestation. Human serine-threonine kinase 4 (STK4) deficiency affects the immune system with recurrent bacterial and viral infections, mucocutaneous candidiasis, cutaneous warts, skin abscesses, T- and B-cell lymphopenia, and neutropenia. PATIENT CONCERN: In this study we describe the infrequent incidence and successful treatment of sinusoidal diffuse large B-cell lymphoma in a STK4 deficient patient with clinical manifestation of severe intractable headaches, unilateral swelling of her face, nasal congestion, stuffiness, and pain in maxillary. DIAGNOSIS: Clinical data including headaches, unilateral swelling of face, nasal congestion, stuffiness and pain in maxillary sinus with confirmed histopathology and magnetic resonance imaging finding confirmed sinusoidal diffuse large B cell lymphoma in a STK4 deficient patient. INTERVENTION: Six cycles of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone) were administered and after each cycle, G-CSF support was used. Chemotherapeutic drugs were administered with standard dose and no dose reduction was done during the treatment. IVIG treatment continued during the courses of chemotherapy. OUTCOME: The index patient achieved complete response at the end of chemotherapy courses and was in remission for about 8 months afterward, prior to the date of the present report. CONCLUSION: PID patient are often at increased risk of malignancies. Sinusoidal diffuse large B-cell lymphoma is quite rare and prognosis is variable. Early attention to patient's manifestation, suitable treatment, and monitoring manifestations caused by PID are critical.

Impact of induction chemotherapy and socioeconomics on sinonasal undifferentiated carcinoma survival.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is an uncommon malignancy of the nasal cavity and accessory sinuses with limited available studies evaluating role of induction chemotherapy (IC), demographics, and socioeconomic factors on overall survival (OS). METHODS: The 2004-2015 National Cancer Database was queried for patients with histologically confirmed SNUC. IC was defined as chemotherapy administered 6 months to 2 weeks before surgery or ≥45 days before radiotherapy. RESULTS: Of 440 identified patients, 70 (16%) underwent treatments involving IC. This consisted of 52 (12%), 15 (3%), and 3 (1%) patients receiving IC before definitive radiation therapy, surgery and adjuvant radiotherapy, or surgery only, respectively. On univariate analysis, IC (p = 0.34) did not affect OS, whereas having government insurance (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.37-2.34; p < 0.001) and living in regions with ≥13% of the population without a high school diploma (HR, 1.38; 95% CI, 1.06-1.79; p = 0.02) were associated with worse OS. On log-rank test, patients with advanced stage had similar OS regardless of whether or not they received IC (p = 0.96). Patients who received IC lived closer to their treatment site (p = 0.02) and had worse overall health, with more comorbidities (p = 0.02). The timing of IC before definitive surgery or radiation did not affect OS (p = 0.69). CONCLUSION: In this SNUC population-based analysis, IC did not appear to provide additional OS benefit regardless of disease stage or timing before definitive treatment. Distance to treatment and level of comorbidities may be associated with receiving IC, whereas type of insurance and residence education level may impact SNUC OS, regardless of treatment.

Identification of markers predictive for response to induction chemotherapy in patients with sinonasal undifferentiated carcinoma.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare, highly aggressive cancer. Despite aggressive multimodal therapy, its prognosis remains poor. Because of its locally advanced nature and high propensity for distant metastasis, we frequently use induction chemotherapy before definitive therapy in patients with SNUC. However, about 30% of patients do not respond to induction chemotherapy, and lack of response is associated with a poor survival rate. Therefore, in this study, we performed gene expression analysis of SNUC samples to identify prognostic markers for induction chemotherapy response. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded SNUC tumor samples from previously untreated patients harvested before induction chemotherapy were used. Gene expression was performed using an oncology gene expression panel. RESULTS: We identified 34 differentially expressed genes that distinguish the responders from the non-responders. Pathway analysis using these genes revealed alteration of multiple pathways between the two groups. Of these 34 genes, 24 distinguished between these two groups. Additionally, 16 gene pairs were associated with response to induction therapy. CONCLUSION: We identified genes predictive of SNUC response to induction chemotherapy and pathways potentially associated with treatment outcome. This is the first report of identification of predictive biomarkers for response of SNUC to induction chemotherapy, and it may help us develop therapeutic strategies to improve the treatment outcomes of non-responders.

Therapeutic efficacy of regional and systemic chemotherapy in advanced maxillary sinus cancer.

BACKGROUND: To compare the efficacy of regional chemotherapy through the superficial temporal artery and systemic chemotherapy in patients with advanced maxillary sinus cancer. METHODS: Nine of 22 patients with over TNM stage III maxillary sinus cancer received regional chemotherapy and 13 received systemically. The change of tumor volume, the degree of response according to the tumor location, and side effects after chemotherapy were analyzed. RESULTS: Tumor volume reduction was significantly higher in the regional than systemic chemotherapy. Tumor response to chemotherapy was greater in regional than systemic chemotherapy in most maxillary sinus wall. The tumor response in anterior, posterior, and lateral wall of maxillary sinus was greater more than two times in the regional than systemic chemotherapy. There were no severe side effects related to regional chemotherapy. CONCLUSION: Regional chemotherapy was superior to systemic chemotherapy regarding tumor volume reduction, especially located in the anterior, posterior, and lateral wall of maxillary sinus.

Definitive Radiation Therapy Versus Postoperative Radiation Therapy for Patients With Maxillary Sinus Cancer Invading the Upper Jaw.

Maxillectomy following radiation therapy has the strongest local control over maxillary sinus cancer. However, in the advanced stage, complete resection is difficult with adequate margin and has the risk of functional disabilities after surgeries. The objective of the study was to determine the optimal treatment strategy for patients with maxillary sinus cancer invades the upper jaw. A total of 998 histologically confirmed maxillary sinus cancer invades the upper jaw patients were subjected to simple randomization. Patients were subjected to maxillectomy and received 150 mg/m/wk intra-arterial cisplatin for 4 weeks followed by radiotherapy (PR group, n = 499) or received the same chemotherapy and definitive radiotherapy only (DR group, n = 499). Disease status, overall survival, progression-free survival, and treatment-emergent adverse effects were evaluated in the follow-up period of 5 years. At the end of 5 years of follow-up, both the treatments had the same overall survival (P = 0.066). Demographic characters were independent parameters for the overall survival (P ≥ 0.05 for all). Postoperative radiotherapy had a higher progression-free survival than definitive radiotherapy (P = 0.018). Maxillectomy was useful in the reduction of the evidence of local recurrence of cancer (P = 0.027). Dysphagia, palate fistula, incomprehensible voice, and trismus were reported as treatment-emergent effects in the PR group. Definitive radiation therapy is recommended in maxillary sinus cancer that invades the upper jaw (Level of Evidence: I; research registry 4571 dated November 14, 2012).

MLL rearranged acute lymphoblastic leukaemia presenting as a maxillary sinus mass with a discordant immunophenotypic profile from the bone marrow.

We describe an unusual case of pre-B lymphoblastic leukaemia presenting with a unilateral maxillary sinus mass in which biopsies of the primary mass and the bone marrow demonstrated conflicting immunophenotyping results. The extramedullary mass was consistent with a precursor B-cell malignancy, while the bone marrow was initially reported as a possible mature B-cell malignancy. The treatments for the two are fundamentally different, which necessitated a delay in the initiation of his chemotherapy until a clear diagnosis was made. Mixed lineage leukaemia gene rearrangement was confirmed by fluorescence in situ hybridisation in both the primary mass and bone marrow, which unified the diagnosis as pre-B acute lymphoblastic leukaemia given the common cytogenetic feature.

Clinical characteristics and treatment outcomes of natural killer/T-cell lymphoma involving the ocular adnexa.

AIMS: To evaluate the clinical characteristics and treatment outcomes of natural killer/T-cell lymphoma (NKTL) involving the ocular adnexa. METHODS: Retrospective, comparative, observational case series. A total of 350 patients with NKTL, including 27 patients with NKTL involving the ocular adnexa from 1999 to 2016. The patients were grouped into two groups: group 1 comprised patients presenting with ophthalmic symptoms, and group 2 comprised patients presenting with symptoms from other organs but subsequently developed ophthalmic involvement. RESULTS: Group 1 comprised 12 patients (44.4%) and group 2 comprised 15 (55.6%). Mean duration of symptoms in group 1 was 1.8±1.2 months, while the time from diagnosis of NKTL to development of ophthalmic symptoms in group 2 was 45.3±65.6 months. Periorbital swelling was the most common presenting symptom in both groups (83.3% in group 1 and 73.3% in group 2). Symptoms mimicking cellulitis and pseudotumor were present in 50.0% and 16.7% of cases, respectively. The 5-year overall survival rate was 18.5% in group 1 and 26.4% in group 2, while the 5-year progression-free survival rate was 0% and 13.3%, respectively. CONCLUSIONS: Our series is to our knowledge the largest cohort study on NKTL reported to date and demonstrates that ocular adnexal NKTL is a rare but seriously fatal disease. It is characterised by acute inflammatory signs as present in as many as two-thirds of our patients in this series. It should be considered as a differential diagnosis in patients presenting with rapidly progressing proptosis and diagnosed promptly for optimal management.

Clinical T staging is superior to fluorodeoxyglucose positron emission tomography for predicting local outcomes after intra-arterial infusion chemoradiotherapy for maxillary sinus squamous cell carcinoma.

Concomitant intra-arterial infusion chemoradiotherapy (IA-CRT) has been used to treat locally advanced maxillary sinus squamous cell carcinoma (MSSCC) with positive outcomes. However, an optimal predictive prognostic factor for MSSCC treated with IA-CRT remains elusive. The aim of the present study was to assess the feasibility of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), including volumetric parameters, to predict the prognosis of MSSCC treated with IA-CRT. Twenty-four patients with newly diagnosed MSSCC receiving FDG-PET imaging before IA-CRT treatment were analyzed in this retrospective study. All patients underwent radiotherapy with a total tumor dose of 60-66 Gy in a conventional fractionation schedule, using three-dimensional conformal radiation therapy or intensity-modulated radiation therapy. Radiotherapy was performed concurrently with concurrent intra-arterial infusion chemotherapy (cisplatin). The IA-CRT response rate was 83.33%. The 1- and 3-year survival rates were 81.30% and 64.34%, respectively. The 1- and 3-year local failure-free rates were 57.21% and 40.96%, respectively. Local failure was significantly associated with poor survival (P = 0.0152). Further, clinical T staging clearly stratified local control outcomes among patients with clinical T3 or less, T4a, and T4b (P = 0.0312). Moreover, patients with stage T4b showed a significantly poorer local control compared with T3 or less (P = 0.0103). However, FDG-PET parameters provided no significant predictive information regarding treatment outcome. To conclude, pretreatment T stage predicts local control by IA-CRT, which is associated with survival.

Clinical study of cetuximab combined with radical radiotherapy in the treatment of locally advanced sinonasal squamous cell carcinoma.

PURPOSE: To observe the efficacy and side effects of cetuximab combined with radical radiotherapy in the treatment of sinonasal squamous cell carcinoma (SCC), and to investigate the underlying mechanism of cetuximab. METHODS: 62 patients with locally advanced sinonasal SCC diagnosed in our hospital from January 2013 to January 2014 were enrolled. Cetuximab and radical radiotherapy were simultaneously given to patients in the combination group, while only radical radiotherapy was given to patients in the radiotherapy group. Cetuximab was administered weekly until the end of radiotherapy. Patients intolerant to cetuximab or withdrawn the informed consent were excluded. On first administration, cetuximab was given i.v. at a dose of 400 mg/m2 for more than 120 min, with maximum drop rate of 5 mL/min. Afterwards, cetuximab was given i.v. per week at a dose of 250 mg/m2 for more than 60 min. RESULTS: (1) The objective response rate (ORR) and disease control rate (DCR) in the combination group was 77.42% and 93.54%, respectively, while the ORR and DCR in the radiotherapy group were only 45.61% and 70.97%, respectively (p<0.05). (2) The progression free survival (PFS) and the median overall survival (OS) in the combination group were 19.5 and 26.6 months, respectively, while in the radiotherapy group were only 13.8 and 18.9 months, respectively (p<0.05). (3) The incidence of rash in the combination group was significantly higher than that of the radiotherapy group (p<0.05). However, there were no significant differences in other adverse reactions between the two groups. CONCLUSIONS: Combination of cetuximab with radical radiotherapy is safe and effective for advanced local sinonasal SCC and improves the survival rate and the prognosis of patients with sinonasal SCC.

Recurrent fibrosarcoma of maxillary sinus involving the cranial base: A rare case.

Adult fibrosarcoma (FS) of the maxillary sinus and the cranial base is a rare soft tissue sarcoma which is clinically characterized by a high frequency of local repeated recurrence if not excised widely. At present, the standard treatment option for FS is surgical resection. Here, we report a case of a 46-year-old male with a 5 months history recurrent FS of the maxillary sinus. The patient possessed an enormous mass in the right maxillofacial region extending to the cranial base, as observed by computed tomography. Histologically, the lessions were composed of hypercellular cells with heterogenous groups. The recurrence and pathologically heterogenous groups of FS lead to therapeutic complexities. Due to the challenging anatomy in head and neck region, it is crucial to define the lesion areas and weigh the balance between life quality and functional reconstruction.

Treatment outcomes of locally advanced squamous cell carcinoma of the maxillary sinus treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation: Implications for prognostic factors.

BACKGROUND: This study clarified the clinical results of locally advanced squamous cell carcinoma of the maxillary sinus (SCC-MS) that was treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation (RADPLAT). Prognostic factors were also investigated. METHODS: We retrospectively analyzed 63 locally advanced SCC-MS patients treated with initial RADPLAT followed by sequential RADPLAT (S-RADPLAT) or surgery. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates of patients with T3, T4a, or T4b disease were 72.2%, 46.6%, and 33.3% (p = 0.104) and 83.3%, 51.6%, and 33.3% (p = 0.031), respectively. The 5-year PFS and OS rates of the S-RADPLAT or surgery groups with T4 disease were 39.6% and 60.6% (p = 0.199) and 44.7% and 63.3% (p = 0.276), respectively. Tumor extension into the medial and/or lateral pterygoid muscle (p < 0.001) and N classification (p = 0.012) were considered significant factors for PFS. Regarding OS, tumor extension into the medial and/or lateral pterygoid muscle (p = 0.005) was considered a statistically significant risk factor. CONCLUSIONS: It may be better for T4 non-responders to initial RADPLAT to undergo surgery. Patients with high risk factors of positive neck metastasis or pterygoid muscle extension may need adjuvant chemotherapy.

Medical therapy of maxillary sinus inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumor (IMT) in the maxillary sinus is a diagnostic challenge. As IMT has various names, it has various findings in magnetic resonance image. Although destructive pattern in computed tomography and hypermetabolism in PET CT suggest malignancy, it is debatable whether it is a tumor or inflammatory lesion. Treatment of IMT usually includes surgery. However, IMT can be dealt with medical treatment according to histologic type and localization. We report a rare case of IMT in the maxillary sinus which is controlled by medical therapy.

Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma.

BACKGROUND: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive cancer. Despite multimodal therapy, the prognosis in SNUC remains poor, and new therapies are needed. Thus, the purpose of this study was to explore potential therapeutic targets in SNUC. METHODS: Using the human-derived SNUC MDA8788-6 cell line, we performed whole genome single nucleotide polymorphism (SNP) analysis to identify copy number changes in this line. Protein expression levels were evaluated by Western blotting. Cell growth inhibition was assessed by methylthiazol tetrazolium (MTT) and clonogenic assays. The mouse flank model was used to examine the effect of growth inhibition in vivo. RESULTS: The ERBB2 gene was highly amplified and cell extracts showed human epidermal growth factor receptor 2 (HER2) was overexpressed and phosphorylated in MDA8788-6. Lapatinib effectively inhibited the HER2 signaling pathway in our SNUC cell line. HER2 inhibition successfully suppressed the cell growth of MDA8788-6 cells both in vitro and in vivo. CONCLUSION: Targeting HER2 may be a promising avenue for the development of novel therapies for SNUC. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1926-E1934, 2016.