Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.

Cervical lymph node metastasis is common in patients with nasopharyngeal carcinoma (NPC), but occipital lymph node metastasis in NPC patients has not yet been reported. In this case report, we describe an NPC patient with occipital lymph node metastasis. The clinical presentation, diagnostic procedure, treatment, and outcome of this case were presented, with a review of the related literature.

For patients with nasopharyngeal carcinoma (NPC) who undergo re-irradiation with intensity-modulated radiotherapy (IMRT), lethal nasopharyngeal necrosis (LNN) is a severe late adverse event. The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC. Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study. Clinical characteristics, including recurrent carcinoma conditions and dosimetric features, were evaluated as candidate risk factors for LNN. Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model. Among 228 patients enrolled in this study, 204 were at risk of developing LNN based on risk analysis. Of the 204 patients treated, 31 (15.2%) developed LNN. Logistic regression analysis showed that female sex (P = 0.008), necrosis before re-irradiation (P = 0.008), accumulated total prescription dose to the gross tumor volume (GTV) ≥145.5 Gy (P = 0.043), and recurrent tumor volume ≥25.38 cm3 (P = 0.009) were independent risk factors for LNN. A model to predict LNN was then constructed that included these four independent risk factors. A model that includes sex, necrosis before re-irradiation, accumulated total prescription dose to GTV, and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined. Patients with stage III–IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates. Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3–4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively. Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted. This trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060 .

The aim of this study was to investigate the prognostic significance and various classifications for anatomic masticator space involvement (MSI) in patients with nasopharyngeal carcinoma (NPC). This study retrospectively analyzed 742 patients with untreated nondisseminated NPC who underwent magnetic resonance imaging (MRI) scan of the nasopharynx and neck. The MSI was graded according to different anatomic features. The overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) of the patients with different MSI grades were analyzed using the Kaplan-Meier method and log-rank tests. The frequency of MSI was 24.1% (179/742). The 5-year OS, LRFS, DMFS, DFS for NPC patients with versus without MSI were 70.9% versus 82.5% (P = 0.001), 94.1% versus 91.4% (P = 0.511), 81.4% versus 88.7% (P = 0.021), and 78.0% versus 83.5% (P = 0.215), respectively. Significant differences in OS were also found among different MSI groups. In the patients with MSI, the OS of the group with medial and/or lateral pterygoid involvement (MLPI) NPC was 73.9% compared to 51.3% (P < 0.0001) in the patients with infratemporal fossa involvement (IFI). MSI was an independent prognostic factor for OS and DMFS. NPCs invading the masticator space should be separately categorized into MLPI and IFI prognostic groups. We suggest that MLPI should be staged as T3 while IFI is staged as T4 disease in future TNM staging revision.

Background: The purpose of this study was to evaluate the prognostic value of cranial nerve (CN) palsy in nasopharyngeal carcinoma (NPC) patients. Methods: A retrospective analysis was performed on CN involvement using medical records of 178 consecutive patients with histologically diagnosed, non-disseminated NPC. Results: In 178 NPC patients with CN palsy, the 5-year survival rates were as follows: overall survival (OS), 61.0%; disease-specific survival (DSS), 69.6%; local relapse-free survival (LRFS), 75.2%; distant metastasis-free survival (DMFS), 73.4%; and disease-free survival (DFS), 55.3%. Significant differences were observed in the 5-year OS rates between patients with single and multiple CN palsy (69.8% vs. 54.3%; P = 0.033) and the OS rates between patients with different pretreatment durations (68.7% vs. 43.3%, P = 0.007). However, no significant differences were observed in OS, DSS, LRFS and DFS rates between patients with upper and lower CN palsy (P = 0.581, P = 0.792, P = 0.729 and P = 0.212, respectively). The results showed that recovery duration was an independent prognostic factor for OS (HR = 2.485; P < 0.001), DSS (HR = 2.065; P = 0.016), LRFS (HR = 3.051; P = 0.001) and DFS (HR = 2.440; P < 0.001). Conclusions: Recovery duration is an independent prognostic factor for NPC patients with CN palsy and is related to recurrence, which leads to poor survival. Recovery duration requires close surveillance and different treatment regimens.