Therapeutic Evaluation of Induction Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma With Low-risk N Stage : A Multicenter Retrospective Study From Nonendemic Region of China.

OBJECTIVES: The role of induction chemotherapy (IC) remains ambiguous in a patient with T3-4N0-1 nasopharyngeal carcinoma (NPC) according to data from the endemic area of China. Here, we conducted a multicenter retrospective study to investigate the value of adding IC to concurrent chemoradiotherapy (CCRT) for T3-4N0-1 NPC from Northwest China. METHODS: Data were extracted in 3 hospitals from Northwest China between May 1, 2010 and August 30, 2018. The Kaplan-Meier method was used to estimate the endpoints. Survival curves were compared using the log-rank test. Initial propensity matching was conducted with a 1:1 match of IC + CCRT to CCRT. The primary endpoint of this study was overall survival (OS). RESULTS: A total of 108 patients with staging T3-4N0-1 were included in this study. The median follow-up time was 50 months (range: 6 to 118 months). IC followed by CCRT did not significantly improve OS compared with CCRT in the whole cohort (89.5% vs 77.6%, hazard ratio: 0.41, 95% CI: 0.16-1.04, P = 0.100). But significantly better OS was found when a well-balanced propensity score-matched cohort was analyzed. Adjusted 4-year OS was 89.5% for IC followed by CCRT versus 71.1% for CCRT (hazard ratio: 0.30, 95% CI: 0.11-0.80, P = 0.027). No significant differences were detected in side effects between the two groups. CONCLUSION: This study suggested IC followed by CCRT had the potential to further improve OS in patients with T3-4N0-1M0 NPC from Northwest China compared with CCRT. However, prospective studies with a large sample are warranted to confirm the results.

A novel immune checkpoint-related gene signature for predicting overall survival and immune status in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype and only some of patients could benefit from the immunotherapy. The present study aims to investigate the expression pattern and prognostic value of immune checkpoint genes (ICGs) in TNBC and develop a novel ICGs-signature to predict the prognosis and immune status in TNBC. Methods: ICGs expression profiles and clinical characteristics of TNBC samples were obtained from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was employed to construct a multi-gene signature for predicting the prognostic outcome. The risk scores were calculated based on the coefficients of each ICG in LASSO-Cox regression model. The median score was considered as the cut-off value to divide the TNBC patients into a high-risk group and a low-risk group. The Kaplan-Meier survival curves were generated to further explore the association between the risk scores and prognostic outcomes. Finally, single sample gene set enrichment analysis (ssGSEA) was conducted to evaluate the immune status and immunophenoscore (IPS) score was used for the quantitative evaluation of tumor immunogenicity. Results: PDCD1, PDCD1LG2 and KIR3DL2 were included in the ICGs-signature model and the risk scores were calculated for each sample according to the coefficients in LASSO-Cox regression. Patients in high-risk group were associated with unfavorable prognosis. The receiver operating characteristic (ROC) curves showed the area under the curve (AUC) values for predicting 1-, 2- and 3-year overall survival (OS) by ICGs-signature were 0.925,0.822 and 0.835, respectively. The adaptive immunity cells and innate immunity cells were significantly abundant in the low-risk group, and low-risk patients tended to have higher IPS scores of PD-1, CTLA4, PD-L1 and PD-L2. Conclusions: A novel ICGs-signature was developed and validated, which may be not only served as a robust prognostic marker, but also a potential indicator reflecting immunotherapy response.

Residual Volume of Lymph Nodes During Chemoradiotherapy Based Nomogram to Predict Survival of Nasopharyngeal Carcinoma Patient Receiving Induction Chemotherapy.

PURPOSE: To accurately stratify nasopharyngeal carcinoma (NPC) patients who were benefit from induction chemotherapy (IC) followed by chemoradiotherapy (CCRT), we established residual volume of lymph nodes during chemoradiotherapy based nomogram to predict survival for NPC patients. METHODS: Cox regression analysis were used to evaluate predictive effects of tumor volume parameters. Multivariate Cox regression analysis was used to identify the prognostic factors, and nomogram models were developed to predict survival of NPC patients receiving IC followed by CCRT. RESULTS: Compared with other tumor volumetric parameters, midRT GTVnd was the best predictive factor for OS (HR: 1.043, 95%CI: 1.031-1.055), PFS (HR: 1.040, 95%CI: 1.030- 1.051), and DMFS (HR: 1.046, 95%CI: 1.034 - 1.059) according to the HR of Cox regression analysis. Based on multivariate analysis, three nomograms included midRT GTVnd were constructed to predict 4-year survival. The C-index of nomograms for each survival endpoints were as follow (training cohort vs. validation cohort): 0.746 vs. 0.731 for OS; 0.747 vs. 0.735 for PFS; 0.768 vs. 0.729 for DMFS, respectively. AUC showed a good discriminative ability. Calibration curves demonstrated a consistence between actual results and predictions. Decision curve analysis (DCA) showed that the nomograms had better clinical predictive effects than current TNM staging system. CONCLUSION: We identified the best volumetric indicator associated with prognosis was the residual volume of lymph nodes at the fourth week of chemoradiotherapy for patients receiving IC followed by CCRT. We developed and validated three nomograms to predict specific probability of 4-year OS, PFS and DMFS for NPC patient receiving IC followed by CCRT.

Long-term survival outcomes and adverse effects of nasopharyngeal carcinoma patients treated with IMRT in a non-endemic region: a population-based retrospective study.

OBJECTIVES: To evaluate the long-term survival outcomes and adverse effects of intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to summarise the experiences of IMRT in NPC in the past few decades in non-endemic northwest China. DESIGN: A population-based retrospective study. SETTING: An experience of using IMRT in non-endemic region of China. PARTICIPANTS: The study included 792 newly diagnosed and non-metastatic NPC patients who received IMRT from January 2006 to September 2018 in Xijing Hospital. OUTCOME MEASURES: The survival outcomes, adverse effects and failure patterns were evaluated by univariate, multivariate and subgroup analyses. RESULTS: With a median follow-up time of 46.2 months, the 5-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, disease-free survival (DFS) and overall survival (OS) rates were 90.8%, 97.0%, 82.8%, 69.6% and 78.0%, respectively. Multivariate analysis showed that age, N stage, clinical stage, pathological type and primary tumour volume of more than 23 cm3 were the independent prognosis factors for DFS (all p<0.05); age, N stage, pathological type, cervical lymph node necrosis, and anaemia were significantly associated with OS (all p<0.05). The most common acute toxicities of IMRT were dermatitis, mucositis and dysphagia. Xerostomia and hearing impairment were the top two late toxicities. The main failure patterns were distant metastasis and local and/or regional relapses. CONCLUSIONS: Similar survival, toxicities and failure patterns have been observed in patients treated with IMRT in a non-endemic area of China when compared with that in endemic areas. Induction chemotherapy combined with concurrent chemoradiotherapy may benefit locally advanced NPC in non-endemic areas of China.

Prognostic analysis of 152 patients with distant metastasis after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The aim of this study was to analyze the prognostic factors for nasopharyngeal carcinoma (NPC) patients with distant metastasis after intensity-modulated radiotherapy (IMRT), and to provide a further basis for clinical treatment options. METHODS: One hundred and fifty-two NPC patients with distant metastasis after IMRT from January 2006 to December 2017 were included in this study and reviewed for analysis. The patients were followed up for a median time of 43 months. The survival rate was calculated and compared using the Kaplan-Meier method and log-rank tests, respectively. The Cox risk ratio model was used for univariate and multivariate analyses. RESULTS: Among all patients, the median interval from treatment completion to distant metastasis was 11.3 months. The median post-metastasis survival was 14 months, and the 1-, 2-, and 3-year survival rates were 60.4%, 40.2%, and 27.6%, respectively. Through univariate analysis, we found that overall survival was related to lymph node (N) staging at diagnosis, whether induction chemotherapy was utilized, the interval time from initial radiotherapy completion to distant metastasis, with/without liver metastasis, and whether chemotherapy or palliative radiotherapy were utilized after metastasis discovery. Cox regression results showed that liver metastasis, multi-organ metastasis, chemotherapy after metastasis, and the time from radiotherapy completion to distant metastasis were independent prognostic factors for patient survival. CONCLUSIONS: The prognosis of NPC patients with distant metastasis after IMRT was related to the time from radiotherapy completion to distant metastasis, liver and multi-organ metastasis, and whether adjuvant chemotherapy was administered. Both adequate adjuvant chemotherapy and palliative radiotherapy could potentially prolong the patients' survival.

Detailed analysis of recovery process of cranial nerve palsy after IMRT-based comprehensive treatment in nasopharyngeal carcinoma.

BACKGROUND: Cranial nerve (CN) palsy due to cancer involvement has been considered as an unfavorable prognostic factor for patients with nasopharyngeal carcinoma (NPC). We assessed the role of IMRT based treatment on the recovery of CN palsy and investigated the prognostic value of complete recovery of CN palsy. METHODS: A total of 115 NPC patients with cancer-related CN palsy were included in the study. We referred CTCAE version 5.0 to evaluate the grade of CN palsy. RESULTS: All patients with grade 1 CN palsy recovered completely during the 2 years of follow-up after definite treatment. Most grade 2 palsy could change gradually to grade 1 palsy or complete recovery during 2 years of follow-up. Patients with more than 2 symptoms of CN palsy had poor 3-year disease-free survival (DFS) than these with 1 or 2 symptoms (60.3% vs. 84.9%, HR 0.25, 95% CI 0.07-0.89, P = 0.001). There were no significant differences for PFS, OS, DMFS and LRFS between patients with complete recovery and non-complete recovery from CN palsy after receiving IMRT based comprehensive treatment. CONCLUSIONS: IMRT based comprehensive treatment could effectively promote the recovery of tumor-related CN palsy for NPC patient. More than 2 symptoms of CN palsy was a poor prognostic factor for DFS of NPC patients. The prognostic role of complete recovery of CN palsy was not identified in our study.

Induction chemotherapy followed by concurrent chemoradiotherapy is benefit for advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes.

Given the potentially distinctive histological variations in northwest of China, the aim of current study was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) with concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients with different histological types. A total of 301 patients were included in this study. Patients were classified in two cohorts according to the 2005 WHO World Health Organization histological classification: WHO type IIa group and WHO type IIb group. The Kaplan-Meier method was used to detect the efficacy between IC + CCRT and CCRT in two WHO types cohorts. Propensity score matching method was adopted to balance the baseline covariate and eliminate potential selection bias. On propensity matched analyses, IC + CCRT was found to produce better 3-year DMFS and OS than CCRT in WHO type IIa cohort (DMFS, 76.2% vs. 42.2%, p = 0.029; OS, 78.3% vs. 65.5%, p = 0.027). For WHO type IIb cohort, IC + CCRT was associated with a better 3-year OS (87.4% vs. 77.9%, p = 0.029) and a trend of better 3-year DMFS (85.9% vs. 76%, p = 0.162) compared with CCRT. IC + CCRT was benefit for advanced stage nasopharyngeal carcinoma with different nonkeratinizing carcinoma subtypes.

Induction chemotherapy for the treatment of non-endemic locally advanced nasopharyngeal carcinoma.

BACKGROUND: The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). RESULTS: With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed. MATERIALS AND METHODS: We retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns. CONCLUSIONS: These results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes.

Prognostic Model of Death and Distant Metastasis for Nasopharyngeal Carcinoma Patients Receiving 3DCRT/IMRT in Nonendemic Area of China.

Few studies were conducted to explore the prognostic factors for nonendemic nasopharyngeal carcinoma (NPC) in the era of 3-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the potential prognostic factors for nonendemic NPC.Between January 2004 and December 2011, a total of 393 nonendemic NPC patients receiving 3DCRT/IMRT were reviewed according to the inclusion and exclusion criteria. The prognostic factors we analyzed included age, T stage, N stage, lymph node diameter, primary tumor volume, WHO histology types, and cranial nerve related symptoms. All patients were staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) system. The factors found to be associated with the endpoints by univariate analyses were then entered into multivariate Cox proportional hazards regression analysis.The median follow-up time was 61.4 months (range: 4-130 months). The 5-year local recurrent-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis free survival (DMFS), and disease-specific survival (DSS) for all patients were 89.3%, 96.4%, 73.5%, and 74.3%, respectively. Multivariate analysis indicated that N stage (N2-3), WHO pathologic type II, and primary tumor volume (>23 mL) were 3 independent prognostic factors for DSS and DMFS. According to the number of prognostic factors, patients were divided into 3 risk groups: low-risk group (patients without any risk factors); intermediate-risk group (patients with only 1 risk factor); and high-risk group (patients with more than 2 risk factors). The 5-year DSS for low, intermediate, and high-risk groups were 91.5%, 75.2%, and 49.3%, respectively (P < 0.001). The 5-year DMFS for low, intermediate, and high-risk groups were 89.4%, 77.9%, and 49.4%, respectively (P < 0.001).Advanced N stage (N2-3), larger tumor volume (>23 mL), and histological WHO type II are independently prognostic factors for nonendemic NPC patients in China.

Early radiotherapy has an essential role for improving survival in patients with stage I-II nasal-type of NK/T cell lymphoma treated with L-asparaginase-containing chemotherapy--a single institution experience.

The purpose of this study was to investigate the role of early radiotherapy in patients with localized-stage nasal-type natural killer (NK)/T cell lymphoma treated with L-asparaginase-containing chemotherapy. Sixty-four patients with stage I-II nasal-type NK/T cell lymphoma were enrolled in this study. All patients received an L-asparaginase-containing regimen. Thirty-four patients received late radiotherapy (RT), which was defined as receiving 6 cycles of prior chemotherapy (CT) followed by RT, and 30 patients received early RT, which was defined as receiving no more than 3 cycles of CT followed by early RT. With a median follow-up of 35 months (range, 12-49 months), 19 patients (29.7 %) died from lymphoma-related causes, and 22 patients (34.4 %) developed local and/or distant relapse. The 3-year overall survival (OS) and progression-free survival (PFS) were 84.2 and 74.3 % for early RT and 57.6 and 55.9 % for late RT, respectively, and these differences were significant (OS, p = 0.027; PFS, p = 0.034). After 2 cycles of initial CT, 58 patients achieved treatment response (complete response and partial response). For the 58 patients, there were still significant differences for 3-year OS and PFS when early RT was compared with late RT (3-year OS 94.4 vs. 58 %, P = 0.005; 3-year PFS 82.9 vs. 56.3 %, P = 0.01). Early RT has an essential role in improving survival for localized-stage nasal-type NK/T cell lymphoma (TCL) patients even when used in combination with L-asparaginase-containing CT. Prospective, randomized studies should to be performed to confirm these results.

Clinical outcomes for early-stage nasopharyngeal carcinoma with predominantly WHO II histology treated by intensity-modulated radiation therapy with or without chemotherapy in nonendemic region of China.

BACKGROUND: The clinical outcomes for early-stage nasopharyngeal carcinoma (NPC) in northwest China were evaluated. METHODS: A retrospective study was performed from 69 patients with NPC patients treated with intensity-modulated radiation therapy (IMRT) with or without chemotherapy. RESULTS: Median follow-up was 34 months. World Health Organization (WHO) type II was the predominant histology (71%). All treatment failures occurred in T2N1 NPCs (14.5%), with metastasis the major reason. The 3-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were 93.3%, 94.1%, and 94.8% respectively. The 3-year survival rate for T2N1 and IMRT alone group were both significantly poorer than the T1N0, T2N0, and T1N1 groups and the chemoradiation group, respectively (p < .05). N1 classification, T2N1 classification, and addition of chemoradiation were significant independent predictors (p < .05). No grade IV toxicities were observed. CONCLUSION: T2N1 classification is a unique subgroup with higher risk of distant metastasis. Improved outcomes of T2N1 NPC with predominantly WHO II histology after chemoradiation has not been reported.

Clinical outcome for nasopharyngeal carcinoma with predominantly WHO II histology treated with intensity-modulated radiation therapy in non-endemic region of China.

OBJECTIVES: To evaluate the clinical outcomes of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC) in Northwest China, including assessments of failure patterns, toxicities and potential prognostic factors. METHODS AND MATERIALS: Between January 2006 and June 2010, 193 newly diagnosed non-metastatic NPCs were treated by IMRT with simultaneous-integrated boost (SIB) technique in Xijing Hospital of Northwest China. Cisplatin-based chemotherapy was offered to 85.5% patients. Acute and late toxicities were graded according to the Radiation Therapy Oncology Group (RTOG) scoring criteria. Prognostic factors were assessed by univariate or multivariate analysis. Statistical analyses were performed on survival and failure patterns. RESULTS: Median follow-up was 34 months. WHO type II was the predominant histology for NPCs (69.9%) in our study group. Twelve patients experienced local regional failure and total distant metastasis occurred in 34 patients, representing the major mode of failure. The 3-year local recurrence-free (LRFS), regional recurrence-free (RRFS), distant metastasis-free (DMFS) and overall survival (OS) rates were 86.6%, 86.7%, 86.4%, and 85.7%, respectively. Multivariate analyses showed N-classification, age (≤ 50 vs. >50) and WHO type (WHO II vs. WHO III) were independent predictors for DMFS, LRFS and OS. Tumor volume (≤ 50 cm(3) vs. >50 cm(3)) and presence of anemia were independent significant prognostic factors for profession-free survival (PFS). No significant difference was observed between different T categories. Acute and late toxicities were mild or moderate. No grade IV toxicities were observed. CONCLUSIONS: WHO II was the predominant histology and a significant poor prognostic factor in our study group, indicating different carcinogenetic pathways of NPC between endemic and non-endemic regions. Our experience of using IMRT in the treatment of NPC in non-endemic region showed excellent locoregional control and favorable toxicity profiles.

Failure patterns and survival in patients with nasopharyngeal carcinoma treated with intensity modulated radiation in Northwest China: a pilot study.

PURPOSE: To evaluate the clinical outcomes and patterns of failure in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiotherapy (IMRT) in Northwest China. METHODS AND MATERIALS: From January 2006 to December 2009, 138 NPC patients were treated at Xijing Hospital. Of them, 25 cases with stage I-II received IMRT only, 113 cases with stage III-IVb received IMRT plus accomplished platinum-based chemotherapy. The IMRT prescribed dose was PTV 68-74 Gy to gross disease in nasopharynx and 66-72 Gy to positive lymph nodes in 30-33 fractions, and high risk and low risk region PTV was 60-63 Gy and 50.4~56 Gy in 30~33 and 28 fractions respectively. Plasma Epstein Barr virus (EBV) DNA load was measured before treatment. The clinical toxicities, outcomes and patterns of failure were observed. RESULTS: The median follow up time was 23 months (range 2 to 53 months). EBV infection positive was only 15.9%. Overall disease failure developed in 36 patients, 99% belonged to stage III/IV disease. Among these, there were 26 distant metastases, 6 local recurrence, and 4 regional recurrence. The 3-year local control rate(LCR), distant metastasis-free survival (MFS), disease-free survival (DFS) and the overall survival (OS) was 93.9%, 79.5%, 70% and 83.1% respectively. Multivariate analyses revealed that age and anemia pre-radiotherapy were independent predictors for OS. CONCLUSION: IMRT with or without chemotherapy can improve the long term survival of NPC patients in Northwest China. Distant metastasis becomes the main cause of treatment failure. Age and anemia before radiotherapy were the main prognosis factors of NPC patients.

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: a prospective randomized controlled multi-center trial.

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. PATIENTS AND METHODS: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I-II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. RESULTS: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P=0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P=0.03). No severe toxicity was reported. CONCLUSIONS: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

Three-dimensional conformal radiation therapy for refractory laryngeal granuloma.

AIMS AND BACKGROUND: The etiology of laryngeal granulomas is often multifactorial and the benefit of pharmacological therapy remains unclear. Anti-reflux treatment is only effective in granulomas definitely induced by gastroesophageal reflux. Steroid inhalation has shown favorable results but it is unclear whether it shortens the healing process. Surgical excision is associated with high recurrence rates. The aim of this study was to evaluate the role of 3-dimensional conformal radiation therapy (3DCRT) in the treatment of refractory laryngeal granuloma. METHODS AND STUDY DESIGN: The study was a retrospective review including all patients presenting to the Department of Radiation Oncology at Xijing Hospital from January 2004 to March 2007. We studied a total of 15 cases of refractory laryngeal granuloma that had recurred ≥2 times. Patients had previously been managed with voice rest, corticosteroids, antibiotics, antacids, surgery and botulinum toxin. All patients accepted surgical excision and immediate adjuvant 3DCRT at a total dose of 15 Gy over 5 days. RESULTS: All patients were successfully treated with surgery and 3DCRT. There has been no granuloma recurrence in 3 years of follow-up. CONCLUSIONS: 3DCRT is a safe and effective therapy for refractory laryngeal granulomas, especially when other methods have failed.