Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: A recursive partitioning risk stratification analysis.

BACKGROUND: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of post-IC EBV DNA. RESULTS: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA ≥ 200 copies/mL, or stage IVA and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVA and post-IC EBV DNA ≥ 200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. The RPA model showed better risk discrimination than either the overall stage or post-RT EBV DNA alone. CONCLUSIONS: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed an RPA model that provides improved risk discrimination over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.

Failure pattern and suggestions for target volume delineation of carcinoma showing thymus-like differentiation treated with intensity-modulated radiotherapy.

BACKGROUND: To review our long-term clinical experience, analyze the failure patterns, and give suggestions for target volume delineation of carcinoma showing thymus-like differentiation (CASTLE) treated with intensity-modulated radiotherapy (IMRT). METHODS: From April 2008 to May 2019, 30 patients with CASTLE treated by postoperative or radical IMRT in our center were retrospectively reviewed. A total dose of 56-60 Gy in 28-30 fractions was prescribed to patients without residual disease and 66 Gy in 33 fractions for patients with residual or unresectable disease. Survival rates were calculated using the Kaplan-Meier method. Treatment-related toxicities were graded by National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.0. RESULTS: Among the 30 patients, 12 (40%) received partial resection or biopsy. Lateral lymph node metastasis was observed in 7 (23.3%) patients. During follow-up, regional lymph node recurrence occurred in 2 patients and distant metastasis in 5 patients. With a median follow-up time of 63.5 months, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 100, 88.9, 78.9, 93.1 and 78.9%, respectively. For patients with no lateral neck node metastasis, prophylactic radiotherapy for lateral neck nodal regions failed to improve RRFS (p = 0.381) and OS (p = 0.153). CONCLUSION: Distant metastasis was the major failure pattern for CASTLE after surgery and IMRT. For patients with no lateral neck node metastasis, the omission of irradiation for lateral neck nodal regions seems to be safe and feasible.

Dosimetry of the brain and hypothalamus predicting acute lymphopenia and the survival of glioma patients with postoperative radiotherapy.

BACKGROUND: The aim of this study was to investigate dosimetric factors for predicting acute lymphopenia and the survival of glioma patients with postoperative intensity-modulated radiotherapy (IMRT). METHODS: A total of 148 glioma patients were reviewed. Acute lymphopenia was defined as a peripheral lymphocyte count (PLC) lower than 1.0 × 109 /L during radiotherapy with a normal level at pretreatment. PLCs with the corresponding dates and dose volume histogram parameters were collected. Univariate and multivariate Cox regression analyses were constructed to assess the significance of risk factors associated with lymphopenia and overall survival (OS). RESULTS: Sixty-nine (46.6%) patients developed lymphopenia during radiotherapy. Multivariate analyses revealed that the risk increased with the maximal dose of the hypothalamus (HT Dmax) ≥56 Gy (58.9% vs 28.5%, P = 0.002), minimal dose of the whole brain (WB Dmin) ≥2 Gy (54.3% vs 33.9%, P = 0.006), or mean dose of the WB (WB Dmean) ≥34 Gy (56.0% vs 37.0%, P = 0.022). Patients with older age, high-grade glioma, development of lymphopenia, high HT Dmax, WB Dmin, and WB Dmean had significantly inferior OS in the multivariate analyses. CONCLUSIONS: HT Dmax, WB Dmin, and WB Dmean are promising indicators of lymphopenia and the survival of glioma patients undergoing postoperative IMRT. The necessity and feasibility of dosimetric constraints for HT and WB is warranted with further investigation.

Basal cell adenocarcinoma of the nasopharyngeal minor salivary glands: a case report and review of the literature.

BACKGROUND: Basal cell adenocarcinomas (BCACs) arise from the minor salivary glands in the upper respiratory tract and are extremely rare. In this report, we present an unusual case of a 57-year-old male with BCAC that arose from the nasopharynx. To our knowledge, this is the first case report of nasopharyngeal BCAC. CASE PRESENTATION: In August 2010, a 57-year-old Chinese male presented with epistaxis and decreased hearing for 1 month. He was diagnosed with BCAC of the solid type that arose from the nasopharynx. The patient received radiotherapy alone and exhibited a complete response. A follow-up at 72 months did not detect any evidence of disease recurrence or metastasis. A comprehensive literature review revealed only 7 previously reported cases of BCAC in the upper respiratory tract. Surgery is the first choice to treat BCAC but may impair maxillofacial function. Radiotherapy is reserved for inoperable cases. CONCLUSIONS: Radiotherapy can achieve good local control and preserve maxillofacial function; therefore, this treatment may be a suitable option for patients who are not good candidates for surgery.

Effects of dosimetric inadequacy on local control and toxicities in the patients with T4 nasopharyngeal carcinoma extending into the intracranial space and treated with intensity-modulated radiotherapy plus chemotherapy.

BACKGROUND: To protect neurological tissues, underdosing occurs in most cases of T4 nasopharyngeal carcinoma (NPC) with intracranial extension. In this study, we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy (IMRT) plus chemotherapy. METHODS: We prospectively enrolled patients who had non-metastatic T4 NPC with intracranial extension treated between January 2009 and November 2013. The prescribed dose was 66.0-70.4 Gy to the primary planning target volume (primary gross tumor volume [GTVp; i.e., the nasopharyngeal tumor] + 5.0 mm). Dose-volume histogram parameters were calculated, including minimum point dose (Dmin) and dose to 95% of the target volume (D95). All patients received chemotherapy with the cisplatin, 5-fluorouracil, and docetaxel regimen. Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 41 patients were enrolled. The local partial response rate was 87.8% after induction chemotherapy. With a median follow-up of 51 months, 7 patients experienced failure in the nasopharynx; the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4% and 90.2%, respectively. The actual mean Dmin to the GTVp was 55.2 Gy (range 48.3-67.3 Gy), and D95 was 61.6 Gy (range 52.6-69.0 Gy). All doses received by neurological organs remained well within their dose constraints. No patients developed temporal lobe necrosis or other neurological dysfunctions. CONCLUSIONS: With relative underdosed IMRT plus effective chemotherapy, the patients achieved satisfactory local control with few late toxicities of the central nervous system. Determining the acceptable extent of dosimetric inadequacy requires further exploration.

Treatment of cerebral radiation necrosis with nerve growth factor: A prospective, randomized, controlled phase II study.

PURPOSE: A prospective, placebo controlled phase II trial was conducted to test the efficacy of Nerve Growth Factor (NGF) for the treatment of symptomatic temporal lobe necrosis (TLN). MATERIALS AND METHODS: Patients with progressive TLN were randomly assigned to either the control or the study group in a 1:1 ratio. The control group received corticosteroids with gradually reduced dosage. The study group received NGF with corticosteroids. NGF was dissolved in 2mL normal saline and injected intramuscularly at 18µg/time, once a day for 2months. The efficacy was evaluated by both the objective and subjective methods every 3-4months after treatment. The objective method compared volumes of the necrotic masses on MRI before and after treatment. The subjective method compared the neurocognitive score as evaluated by the mini-mental status examination (MMSE). RESULTS: Twenty-eight cases were enrolled into this study. The objective evaluation showed that the response rate (RR) in the study group was higher than the control group. The ratio was 10 versus 2 (p=0.006), and 12 versus 3 (p=0.002) at 3-4months and 6-8months after intervention, respectively. The subjective evaluation demonstrated both groups were effective in controlling the necrosis related symptoms in the first 6months after treatment. But NGF was more effective than corticosteroids at 9months (13 versus 4, p=0.001). The only observed side effect was mild pain at the injection site in 3 patients in the study group. CONCLUSIONS: Our results demonstrated that the process of TLN is not irreversible. NGF is more effective in recovering TLN than corticosteroids with little side effect. NGF has a longer duration in controlling the necrosis related symptoms than corticosteroids.

Tumor Regression and Patterns of Distant Metastasis of T1-T2 Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy.

PURPOSE: To study tumor regression and failure patterns in T1-T2 non-metastatic nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: A retrospective analysis of 139 nasopharyngeal carcinoma patients treated with IMRT between January 2005 and December 2010 in our center was performed. According to the AJCC staging system, all primary lesions were attributed to T1 and T2. The prescription doses were 66 Gy at 30 fractions to gross tumor volume of the nasopharynx and the positive neck nodes, 60 Gy to high-risk clinical target volume and 54 Gy to low-risk clinical target volume. Patients staged III, IV A/B or II (lymph node measured 4 cm or more in diameter) received platinum-based chemotherapy. RESULTS: By the end of radiotherapy, 7.2% (10/139), 23.7% (33/139), and 9.4% (13/139) of patients had residual lesions in the nasopharynx, cervical lymph nodes and retropharyngeal lymph nodes, respectively. The majority of patients had complete remission within 6 months of radiotherapy completion. Five months after IMRT, three patients with residual tumors in the cervical lymph nodes underwent surgery. Among these patients, two patients had positive pathological findings, and one patient had negative findings. With a median follow-up of 59 months, the 5-year overall survival, local control, regional control and distant metastasis-free rates were 87.8%, 96.7%, 94.9% and 89.1%, respectively. Fifteen patients developed distant metastases, representing the primary failure pattern. CONCLUSIONS: Most residual lesions that persisted after IMRT vanished completely in six months. Considering the potential damage to normal structures, clinicians should be cautious when considering the use of boost irradiation after radiotherapy. Distant metastasis was the primary cause of treatment failure, which was significantly higher in N2-3 patients than in N0-1. Additional studies to better understand distant metastases are needed.

Study of the medial group retropharyngeal node metastasis from nasopharyngeal carcinoma based on 3100 newly diagnosed cases.

PURPOSE: Patterns of metastases to the medial retropharyngeal lymph nodes (RPLN) from nasopharyngeal carcinoma (NPC) have gain little attention. Since the incidence of dysphagia was closely related to whether the medial RPLN was irradiated, we carried out a prospective study to explore the patterns of the medial RPLN involvement. METHODS AND MATERIALS: Previously untreated NPC patients were required to receive MRI scan. MRI scanning sequences included pre-contrast T1WI, T2WI, and post-contrast T1WI with fat suppression. All images were evaluated by the multi-disciplinary treatment group of NPC. RESULTS: 3100 cases of NPC entered this study. 2679 (86.4%) cases had involved lymph nodes. The detailed distribution were: 2341 (87.4%) in level IIb, 1798 (67.1%) in level IIa, 1184 (44.2%) in level III, 350 (14.1%) in level IV, 995 (37.1%) in level V, 115(4.3%) in level Ib, 2012 (75.1%) in the retropharyngeal area. But only 6 (0.2%) were located at the medial group, accompanied with the lateral RPLN and other node metastasis. Only one medial RPLN can be identified in a patient, whereas the number of the lateral RPLNs per affected side varied between one and four. The average size of the medial and lateral RPLNs was 8±4 mm (range, 4-17 mm) and 16±9 mm (range, 5-53 mm), respectively. CONCLUSIONS: ① Involvement of the retropharyngeal nodes were mainly located at the lateral group, the medial RPLN was rarely seen. ② Metastasis to the medial RPLN was always accompanied with other node metastasis. ③ Only one medial RPLN can be identified in a patient, whereas the enlarged lateral RPLNs per affected side could be multiple. ④ The average size of the medial RPLN was smaller than the lateral RPLNs.

A phase III study of late course accelerated hyperfractionated radiotherapy versus conventionally fractionated radiotherapy in patients with nasopharyngeal carcinoma.

OBJECTIVE: To compare the efficacy and toxicity of late course accelerated hyperfractionated radiotherapy (LCAF) with conventionally fractionated (CF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). METHODS: Between March 1998 and November 2002, 200 eligible patients with NPC were randomized to receive either LCAF (48 Gy in 40 fractions, 2 fractions per day, 1.2 Gy/fraction, with an interval of ≥6 h, 5 d/wk, followed by 30 Gy in 20 fractions using 2 fractions per day, 1.5 Gy/fraction, 5 d/wk) or CF (35 fractions, 2.0 Gy/fraction/d, 5 d/wk, to a total dose of 70 Gy). RESULTS: All patients completed the treatment. Overall baseline characteristics of the study population of the 2 arms were well balanced. With a median follow-up of 6.9 years, the 5-year local control rate was higher in the LCAF arm (87.6% vs. 75.9%, P=0.044). The 5-year overall survival rates were 74.1% vs. 58.0% (P=0.024) for the LCAF arm and the CF arm, respectively. LCAF patients had a higher occurrence of acute mucositis and a more evident weight loss than CF patients, whereas incidence rates of radiation-induced damage to the central nervous system were similar in the 2 arms. CONCLUSIONS: LCAF achieved higher local control and overall survival rates than CF radiotherapy, without increasing radiation-related late complications such as cranial nerve palsy.

Paclitaxel with cisplatin in concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma.

The aim of this study was to evaluate the efficacy and the toxicity of paclitaxel and cisplatin in patients in concurrent radiotherapy for locally advanced nasopharyngeal carcinoma, and to see whether such a regime would be better tolerated than high dose cisplatin plus fluoracil in Chinese patients. Thirty-one patients with locally advanced nasopharyngeal carcinoma were enrolled. Patients were scheduled to receive two courses of concomitant chemotherapy, starting on day 1 and then day 28 during radiotherapy (70-76 Gy in 35-38 fractions in 7-7.5 weeks). Chemotherapy was given by intravenous infusion, paclitaxel 120 mg/m(2) in 3 h, cisplatin 75 mg/m(2) (25 mg/m(2) days 1-3). Adjuvant therapy was paclitaxel 135 mg/m(2) in 3 h, cisplatin 75 mg/m(2) (25 mg/m(2) days 1-3) on weeks 3, 6, 9 after radiotherapy. All patients completed radiotherapy, but for concomitant chemoradiotherapy, 20 of the 31 patients completed the 2 cycles of chemotherapy, while the other 11 could only receive 1 cycle due to various reasons. The median follow-up was 40 months, 2 patients developed locoregional recurrences, one of whom in the cervical lymph nodes, the other in the nasopharynx. The 3-year overall survival rate was 83.9% and the distant metastasis rate at 3 years was 13.6%. Grade 3-4 toxicities were neutropenia 12.9%, anaemia 6.45%, thrombocytopenia 3.22%, severe arrhythmia 3.2%, and hypersensitivity reaction 3.2%. In conclusion, paclitaxel with cisplatin as concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma is feasible, safe, and might improve regional control and survival rates in Chinese patients.

Late course accelerated hyperfractionated radiotherapy of nasopharyngeal carcinoma (LCAF).

BACKGROUND AND PURPOSE: To study the efficacy of late course accelerated fractionated (LCAF) radiotherapy in the treatment of nasopharyngeal carcinoma (NPC). The end-points were local control, radiation-induced complications, and factors influencing survival. PATIENTS AND METHODS: Between December 1995 and April 1998, 178 consecutive NPC patients were admitted for radiation treatment. The radiation beam used was (60)Co gamma or 6 MV X rays. For the first two-thirds of the treatment, two daily fractions of 1.2 Gy were given to the primary lesion, with an interval of > or =6h, 5 days per week to a total dose of 48 Gy/40 fractions, over a period of 4 weeks. For the last third of the treatment, i.e., beginning the 5th week of treatment, an accelerated hyperfractionated schedule was carried out. The dose per fraction was increased to 1.5 Gy, 2 fractions per day with an interval of > or =6h, the total dose for this part of the protocol was 30 Gy/20 fractions over 2 weeks. Thus the total dose was 78 Gy in 60 fractions in 6 weeks. RESULTS: All patients completed the treatment. Acute mucositis: none in 2 cases, Grade 1 in 43 cases, Grade 2 in 78 cases, Grade 3 in 52 cases, and Grade 4 in 3 cases. Local control rate: the 5 year nasopharyngeal local control rate was 87.7%, and the cervical lymph nodes local control rate was 85.7%. The 5-year distant metastasis rate was 26.1%, and 5 year survivals were 67.9%, 16 (9%) patients had radiation-induced cranial nerve palsy, 7(4%) patients had temporal lobe or brainstem damage. CONCLUSIONS: With this treatment schedule, patients' tolerance was good, local control and 5 year survivals were better than conventional fractionation schedules, and radiation-related late complications did not increase, as 5-year survival rates of conventional fractionation radiotherapy were only 58%. Randomized clinical trials are being carried out to further confirm the efficacy of LCAF for nasopharyngeal carcinoma.