Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary.

PURPOSE: To evaluate the long-term local control, failure patterns, and toxicities after individualized clinical target volume (CTV) delineation in unilateral nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). METHODS: Unilateral NPC was defined as a nasopharyngeal mass confined to one side of the nasopharynx and did not exceed the midline. From November 2003 to December 2017, 95 patients were retrospectively included. All patients received IMRT. The CTVs were determined based on the distance from the gross tumor. The contralateral para-pharyngeal space and skull base orifices were spared from irradiation. RESULTS: There were three local recurrences and eight regional recurrences in 10 patients during an 84-month follow-up. All local recurrences were within PGTVnx, and all in-field recurrences. No recurrences were found in traditional high-risk areas including contralateral the para-pharyngeal space and skull base orifices. The 10-year local-recurrence-free survival, regional-recurrence-free survival and overall survival were 96.2%, 90.5% and 84.7%, respectively. The dosimetry parameters of the tumor-contralateral organs were all lower than the values of the tumor-ipsilateral side (P < 0.05). The late toxicities occurred mainly in the tumor-ipsilateral organs, including radiation-induced temporal lobe injury, impaired visuality, hearing loss and subcutaneous fibrosis. CONCLUSION: Individualized CTV delineation in unilateral NPC could yield excellent long-term local control with limited out-of-field recurrences, reduced dose to tumor- contralateral organs and mild late toxicities, which is worthy of further exploration.

Is Surgery an Inevitable Treatment for Advanced Salivary Lymphoepithelial Carcinoma? Three Case Reports.

Lymphoepithelial carcinoma (LEC) of the salivary gland is a rare malignancy which is identical to undifferentiated nasopharyngeal carcinoma. However, most patients are treated with surgery as primary treatment, which is impossible for some very locoregionally advanced patients. And there are few reports of patients treated by an induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) approach. This report describes 3 cases of advanced stage LEC of the salivary gland. All patients presented with a palpable mass of variable duration and underwent induction CCRT. All cases were positive for Epstein-Barr virus-encoded small RNAs. After IC, all cases had reached partial response and all achieved complete response after CCRT. All patients remained local-regional recurrence-free after 6-month follow-up for case 1, 50-month for case 2, and 14-month for case 3 up to our last follow-up. No serious adverse events were found.

Failure patterns and prognostic factors for cervical node-negative nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: To evaluate the failure patterns and prognostic factors in patients with cervical node-negative nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. METHODS: Patients with cervical node-negative NPC treated with IMRT at the Sun Yat-sen University Cancer Center between February 2001 and December 2008 were retrospectively reviewed. The failure patterns, prognostic factors, and efficacy of additional chemotherapy were assessed. RESULTS: The median follow-up time was 78 months for 298 patients. The 5-year local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS) were 95.2%, 99.3%, 94.8%, 89.8%, and 92.9%, respectively. The rate of treatment failure remained high in patients with T4 disease (35.4%, 17/48), including eight of local recurrence, two of nodal recurrence, and seven of distant metastasis. Multivariate analyses showed that the primary gross tumor volume (GTVp) was significantly associated with LRFS, DMFS, FFS, and OS. Subgroup analysis revealed that patients with GTVp ≤ 42.5 cc had better 5-year LRFS (98.7% vs 81.4%, P < .001), 5-year DMFS (97.8% vs 82.5%, P < .001), 5-year FFS (96.1% vs 65.4%, P < .001), and 5-year OS (96.6% vs 78.2%, P < .001) than patients with GTVp > 42.5 cc. However, additional chemotherapy showed no significant survival benefit in stratification analysis. CONCLUSIONS: Cervical node-negative NPC has a good prognosis in the IMRT era, and the primary tumor volume is the most important prognostic factor. Further exploration is needed to determine the optimal treatment strategy for patients with a high tumor burden.

Can neoadjuvant chemotherapy improve survival in stage T3-4N1 nasopharyngeal carcinoma? A propensity matched analysis.

BACKGROUND: To estimate the efficacy of neoadjuvant chemotherapy (NCT) in stage T3-4N1 nasopharyngeal carcinoma (NPC). METHODS: Data on stage T3-4N1 NPC patients treated with concurrent chemoradiotherapy (CCRT) with or without NCT at the Sun Yat-sen University Cancer Center between January 2006 and December 2013 were retrospectively reviewed. Propensity score matching (PSM) was carried out to balance prognostic factors in NCT followed by CCRT (NCT + CCRT) group and CCRT group in a 1:1 ratio. Survival outcomes of matched patients in the two groups were compared, and prognostic factors were identified using Cox regression model. RESULTS: A total of 282 patients were involved in this study, with 136 of NCT + CCRT group and 146 of CCRT group. After PSM, 85 pairs of patients were selected. There were no significant differences in 5-year overall survival (OS), locoregional recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and recurrence-free survival (RFS) between NCT + CCRT group and CCRT group (81.0% vs. 77.5%, P = 0.750; 85.8% vs. 88.1%, P = 0.495; 92.5% vs. 93.9%, P = 0.759; 81.0% vs.77.5%, P = 0.919, respectively). Multivariate analysis found that smoking history (P = 0.044) and T classification (P = 0.027) were independent prognostic factors for OS, lymph node diameter (P = 0.032) was independent prognostic factor for LRFS, positive pretreatment lymph node condition (PLNC), which was defined as the lymph node necrosis or confluent, was independent prognostic factor for DRFS (P = 0.007), and RFS (P = 0.009). Lower 5-year OS (82.7% vs. 94.1%, P = 0.014), DRFS (79.3% vs. 96.2%, P = 0.003), and RFS (62.4% vs. 86.8%, P = 0.001) were found in positive PLNC group compared with negative PLNC group. In terms of toxicities, the incidences of acute hematological Grade 3-4 adverse events (AEs) were higher in NCT + CCRT group compared with CCRT group (P < 0.05), while no significant difference was observed in the rates of non-hematological Grade 3-4 AEs between these two groups (P > 0.05). CONCLUSIONS: Additional NCT is not associated with improved survival outcomes for patients with stage T3-4N1 NPC, but bring increased hematological Grade 3-4 AEs. PLNC is independent prognostic factor in stage T3-4N1 NPC, with positive PLNC correlating with poor survival outcomes.

Late-course accelerated hyperfractionated intensity-modulated radiotherapy for nasopharyngeal adenoid cystic carcinoma: A case report.

Nasopharyngeal adenoid cystic carcinoma is a rare neoplasm characterized by strong local invasiveness and a higher tendency to relapse. Because of the rare cases, there is a little consensus on treatment. We report a case of T3N0 NACC with a positive resection margin treated with postoperative adjuvant radiotherapy. MRI reexamination indicated suspected tumor progression during the course of radiotherapy. In order to improve local control, late-course accelerated hyperfractionated intensity-modulated radiotherapy (LCAF-IMRT) was performed to escalate total dose, which achieved good local control with no significant late toxicity.

Anti-fungal drug itraconazole exerts anti-cancer effects in oral squamous cell carcinoma via suppressing Hedgehog pathway.

AIMS: To investigate the therapeutic potential of itraconazole in oral squamous cell carcinoma (OSCC) and its molecular mechanism. MATERIALS AND METHODS: The in vitro anti-cancer effects of itraconazole was determined by CCK-8 assay and colony formation assay. Transwell and wound healing assays were used to examine cell invasion and migration. The in vivo therapeutic efficacy of itraconazole was assessed by OSCC patient-derived xenograft (PDX) model. Western blot was performed to explore the anti-cancer mechanism. KEY FINDINGS: Itraconazole inhibited cell proliferation and colony formation of OSCC cells in a time and concentration dependent manner; induced cell cycle arrest and apoptosis, as well as inhibited cell invasion and migration. In the OSCC PDX model, itraconazole impeded tumor growth, reduced Ki-67 expression and induced apoptosis. Itraconazole downregulated the protein expression of Hedgehog pathway to inhibit proliferation and migration of oral squamous cell carcinoma cells, which can be revised by recombinant human sonic hedgehog protein (rSHH). SIGNIFICANCE: Itraconazole showed anti-cancer effects on OSCC via inhibiting the Hedgehog pathway.

Prognostic impact of the pretreatment albumin to alkaline phosphatase ratio for nonmetastatic breast cancer patients.

Introduction: Albumin and alkaline phosphatase have been previously demonstrated as independent prognostic factors for various types of cancer. Here, we aimed to explore the potential value of pretreatment albumin to alkaline phosphatase ratio (AAPR) on overall survival (OS) in nonmetastatic breast cancer patients. Methods: A total of 746 nonmetastatic breast cancer patients were enrolled in this study. Receiver characteristic curve was used to analyze the AAPR threshold. Survival analysis was conducted using the Kaplan-Meier method and compared with the log-rank test. Both univariate and multivariate analyses were performed using Cox proportional hazards regression methodology. Results: The optimal cutoff value of AAPR in predicting OS in nonmetastatic breast cancer patients was 0.525. Increased pretreatment AAPR level was related to age at diagnosis (≥60 years vs <60 years, P=0.000), tumor size (T≤2 cm vs T>2 cm, P=0.034), estrogen receptor (positive vs negative, P=0.022), progesterone receptor (positive vs negative, P=0.025), carcino-embryonic antigen (abnormal vs normal, P=0.016), surgery (lumpectomy vs mastectomy, P=0.002), chemotherapy (yes vs no, P=0.004), radiotherapy (yes vs no, P=0.013), endocrine therapy (yes vs no, P=0.027) but not with lymph node involvement, HER-2 status or CA-153. The 5-year OS rate was 80.16% for the low AAPR group and 92.66% for the high AAPR group. Kaplan-Meier analysis indicated that patients with low-AAPR levels had shorter OS than patients with high-AAPR levels (P=0.001). N classification (P<0.05), Ki-67 (HR=3.603, 95% CI=1.046-12.414, P=0.042) and AAPR (HR=0.447, 95% CI=0.205-0.976, P=0.043) were related to OS in multivariate analyses, respectively. Conclusion: AAPR is an independent prognostic factor for OS in nonmetastatic breast cancer patients. Further prospective studies are required to confirm our findings.