5-Hydroxymethylcytosines in circulating cell-free DNA as a diagnostic biomarker for nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the diagnostic value of 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA) for nasopharyngeal carcinoma (NPC) and to develop a diagnostic model. METHODS: Genome-wide 5hmC profiles in cfDNA from 174 NPC patients and 146 non-cancer individuals were analyzed using the 5hmC-Seal technique. A cfDNA 5hmC-based diagnostic model to identify NPC patients was developed using least absolute shrinkage and selection operator (LASSO) logistic regression, and performance was evaluated with receiver operating characteristic (ROC) curves and confusion matrices. RESULTS: The 5hmC-Seal data from patients with NPC showed a different genome-wide distribution than non-tumor samples. Our initial analysis revealed a 12-gene-based 5hmC marker panel to be an accurate diagnostic model effectively distinguishing between NPC samples and non-cancerous samples (training set: area under curve (AUC)= 0.97 [95 % CI: 0.94-0.99]; and test set: AUC= 0.93 [95 % CI: 0.88-0.98]) superior to EBV DNA testing. The diagnostic score performed well in differentiating the non-cancer subjects from early-stage NPC (training set: AUC=0.99 [95 % CI: 0.98-1]; test set: AUC=0.98 [95 % CI: 0.95-1]), and advanced-stage NPC (training set: AUC=0.96 [95 % CI: 0.93-0.99]; test set: AUC=0.93 [95 % CI: 0.88-0.98]). Notably, in EBV-negative patients, the diagnostic scores showed excellent capacity for distinguishing EBV-negative patients with NPC from non-cancer subjects in both the training set (AUC= 0.94 [95 % CI: 0.88-1]) and test set (AUC=0.91 [95 % CI: 0.81-1]). CONCLUSION: 5hmC modifications in cfDNA are promising noninvasive biomarkers for NPC, offering high sensitivity and specificity, particularly for early-stage and EBV-negative NPC.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Identification of prognostic signatures in remnant gastric cancer through an interpretable risk model based on machine learning: a multicenter cohort study.

OBJECTIVE: The purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC). METHODS: Clinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach. RESULTS: Compared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis. CONCLUSIONS: This study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.

Impact of plasma Epstein-Barr virus DNA in posttreatment nasopharyngeal carcinoma patients after SARS-CoV-2 infection.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in southern China. EBV DNA is the most useful biomarker in NPC. However, the value of EBV DNA in posttreatment NPC patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. METHODS: Sixty-four eligible NPC patients were enrolled between December 2022 and February 2023. Patients who met the following criteria were included: had non-metastatic NPC, completed radical treatment, were first firstly infected with SARS-CoV-2 and their EBV DNA changed from undetectable to detectable. RESULTS: At the end of follow-up, 81.25% (52/64) of patients were confirmed not to relapse with undetectable EBV DNA (no-relapse). In addition, 18.75% (12/64) of patients experienced relapse with consistent detection of EBV DNA (yes-relapse). For all 64 patients, the average time from diagnosis of coronavirus disease 2019 (COVID-19) to detection of detectable EBV DNA was 35.41 days (2 to 139 days). For 52 no-relapse patients, the average time from EBV DNA changing from detectable to undetectable was 63.12 days (6 to 147 days). The levels of EBV DNA were greater in yes-relapse patients than that in no-relapse patients, and the average of EBV DNA levels were 1216 copies/ml and 53.18 copies/ml, respectively. Using 62.3 copies/mL as the threshold, the area under the curve for EBV DNA was 0.88 for distinguishing yes-relapse patients from no-relapse patients. The sensitivity and specificity were 81.97% (95% CI 0.71-0.95) and 86.67% (95% CI 0.70-0.95), respectively. CONCLUSION: For NPC patients infected with SARS-CoV-2, EBV DNA alone is insufficient for monitoring relapse after radical therapy. Long-term follow-up and underlying mechanistic investigations of EBV DNA changes are urgently needed.

The application value of LAVA-flex sequences in enhanced MRI scans of nasopharyngeal carcinoma: comparison with T1WI-IDEAL.

Introduction: Magnetic resonance imaging (MRI) staging scans are critical for the diagnosis and treatment of patients with nasopharyngeal cancer (NPC). We aimed to evaluate the application value of LAVA-Flex and T1WI-IDEAL sequences in MRI staging scans. Methods: Eighty-four newly diagnosed NPC patients underwent both LAVA-Flex and T1WI-IDEAL sequences during MRI examinations. Two radiologists independently scored the acquisitions of image quality, fat suppression quality, artifacts, vascular and nerve display. The obtained scores were compared using the Wilcoxon signed rank test. According to the signal intensity (SI) measurements, the uniformity of fat suppression, contrast between tumor lesions and subcutaneous fat tissue, and signal-to-noise ratio (SNR) were compared by the paired t-test. Results: Compared to the T1WI-IDEAL sequence, LAVA-Flex exhibited fewer artifacts (P<0.05), better visualization of nerves and vessels (P<0.05), and performed superior in the fat contrast ratio of the primary lesion and metastatic lymph nodes (0.80 vs. 0.52, 0.81 vs. 0.56, separately, P<0.001). There was no statistically significant difference in overall image quality, tumor signal-to-noise ratio (SNR), muscle SNR, and the detection rate of lesions between the two sequences (P>0.05). T1WI-IDEAL was superior to LAVA-Flex in the evaluation of fat suppression uniformity (P<0.05). Discussion: LAVA-Flex sequence provides satisfactory image quality and better visualization of nerves and vessels for NPC with shorter scanning times.

Physiological and transcriptomic analysis reveals the toxic and protective mechanisms of marine microalga Chlorella pyrenoidosa in response to TiO2 nanoparticles and UV-B radiation.

Concerns have been raised regarding the adverse effects of nanoparticles (NPs) on marine organisms, as an increasing number of NPs inevitably enter the marine environment with the development of nanotechnology. Owing to the photocatalytic properties, TiO2 NPs' toxicity may be aggravated by enhanced UV-B resulting from stratospheric ozone depletion. However, the molecular mechanisms of phytoplankton in response to TiO2 NPs under UV-B remains poorly understood. In this study, we integrated whole transcriptome analysis with physiological data to provide understanding on the toxic and protective mechanisms of marine Chlorella pyrenoidosa in response to TiO2 NPs under UV-B. The results indicated that the changes in gene expression could be related to the growth inhibition and TiO2 NP internalization in C. pyrenoidosa, and several molecular mechanisms were identified as toxicity response to TiO2 NPs and UV-B. Differential expression of genes involved in glycerophospholipids metabolism indicated that cell membrane disruption allowed TiO2 NPs to enter the algal cell under UV-B exposure, although the up-regulation of genes involved in the general secretory dependent pathway and the ATP-binding cassette transporter family drove cellular secretion of extracellular polymeric substances, acting as a barrier that prevent TiO2 NP internalization. The absence of changes in gene expression related to the antioxidant system may be responsible for the severe oxidative stress observed in algal cells following exposure to TiO2 NPs under UV-B irradiation. Moreover, differential expression of genes involved in pathways such as photosynthesis and energy metabolism were up-regulated, including the light-harvesting, photosynthetic electron transport coupled to photophosphorylation, carbon fixation, glycolysis, pentose phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation, indicating that more energy and metabolites were supplied to cope with the toxicity of TiO2 NPs and UV-B. The obtained results provide valuable information on the molecular mechanisms of response of marine phytoplankton exposed to TiO2 NPs and UV-B.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

Prognostic nutritional index and serum lactate dehydrogenase predict the prognosis of nasopharyngeal carcinoma patients who received intensity-modulated radiation therapy.

PURPOSE: This research aimed to evaluate the prognostic significance of baseline prognostic nutritional index (PNI) and lactate dehydrogenase (LDH) for the outcome of individuals diagnosed with non-metastatic nasopharyngeal carcinoma (NPC). METHODS: A retrospective analysis was conducted on data from 810 patients with non-metastatic NPC who underwent intensity-modulated radiation therapy (IMRT) with or without chemotherapy. The best cut-offs for PNI and LDH were identified by X-tile software to be 48.5 and 150, respectively. To find the independent prognostic factors for survival outcomes, univariate and multivariate regression analyses were conducted, and AUCs were used to compare their prognostic values. RESULTS: Multivariate analysis revealed that patients with PNI > 48.5 had better overall survival (OS) (HR: 0.502, P < 0.001), progression-free survival (PFS) (HR: 0.618, P < 0.001), and distant metastasis-free survival (DMFS) (HR: 0.637, P = 0.005). Higher LDH was associated with poorer OS (HR: 1.798, P < 0.001), PFS (HR: 1.671, P < 0.001), and DMFS (HR: 1.756, P < 0.001). The combination of low PNI and high LDH in non-metastatic NPC patients was correlated with poor OS (P < 0.001), PFS (P < 0.001), and DMFS (P < 0.001). The combination of PNI and LDH had the highest AUCs for predicting OS, PFS, and DMFS. CONCLUSIONS: PNI and LDH might become valuable predictors of the prognosis of non-metastatic NPC patients undergoing IMRT with or without chemotherapy. Prognostic accuracy can be enhanced by combining PNI and LDH.

Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma.

Background: The study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC). Methods: Newly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). Results: In this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage. Conclusion: We built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians' abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.

Constructing an individualized surveillance framework for nasopharyngeal carcinoma based on a dynamic risk-adapted approach.

BACKGROUND AND PURPOSE: This study aims to evaluate the dynamic survival and recurrence hazard of nasopharyngeal carcinoma(NPC) patients after definitive chemoradiotherapy utilizing conditional survival(CS) analysis, and to propose a personalized surveillance strategy at different clinical stages. MATERIALS AND METHODS: Non-metastatic NPC patients who received curative chemotherapy between June 2005 and December 2011 were included. The Kaplan-Meier method was used to calculate the CS rate. RESULTS: A total of 1616 patients were analyzed. With the prolongation of survival time, both conditional locoregional recurrence free survival and distant metastatic free survival increased gradually. Changing pattern of annual recurrence risk over time varied among different clinical stages. The annual locoregional recurrence(LRR) risk in stage I-II was always less than 2%, while in stage III-IVa, it was greater than 2% for the first three years and decreased to below 2% only after the third year. The annual distant metastases (DM) risk was always less than 2% in stage I, but higher than 2% in stage II for the first 3 years (2.5-3.8%). For those with stage III-IVa, the annual DM risk retained at a high level(>5%), and only decreased to < 5% after the third year. Based on the dynamic changes in survival probability over time, we established a surveillance plan with different follow-up intensities and frequencies for different clinical stages. CONCLUSION: The annual risk of LRR and DM decrease over time. Our individual surveillance model will provide critical prognostic information to optimize clinical decision-making, and promote to formulate surveillance counseling and help with resources allocation.

Elevated Serum Alpha-Fetoprotein Is a Significant Prognostic Factor for Patients with Gastric Cancer: Results Based on a Large-Scale Retrospective Study.

Objectives: The aim of this work is to study the clinicopathological features and prognostic factors of serum alpha-fetoprotein (AFP)-positive gastric cancer (GC). Methods: A cohort study including 2,318 patients with GC who underwent radical surgery from January 2008 to December 2015 was retrospectively analyzed. Patients were divided into two groups according to preoperative serum AFP values: 191 patients with AFP-positive GC (AFP > 20 ng/ml, 8.24%) and 2,127 patients with AFP-negative GC (AFP ≤ 20 ng/ml, 91.76%). The clinicopathological features and prognostic factors were explored. Results: Compared with AFP-negative GC, AFP-positive GC had higher rates of liver metastasis, lymph node metastasis, venous invasion, and nerve invasion (all P < 0.05). The 5-year OS, DFS, and mLMFS of AFP-positive GC were shorter than AFP-negative GC (55.00% vs. 45.04%, P < 0.001; 39.79% vs. 34.03%, P < 0.001; 13.80 months vs. 16.25 months, P = 0.002). In whole cohort, multivariate analysis found that serum AFP levels (positive vs. negative), pT stage, pN stage, nerve invasion (yes or no), and venous invasion (yes or no) were independent prognostic factors. Serum AFP levels (20-300 ng/ml vs. 300-1,000 ng/ml vs. >1,000 ng/ml), pT stage, pN stage, and venous invasion (yes or no) were independent prognostic factors in AFP-positive GC. Conclusion: Liver metastases and venous invasion are more likely to occur in AFP-positive GC and lead to poor prognosis. Serum AFP level is an independent prognostic factor in patients with GC. As the level of AFP increases, the prognosis becomes worse.

Intraperitoneal infusion of recombinant human endostatin improves prognosis in gastric cancer ascites.

Objective: To investigate the efficacy and safety of intraperitoneal administration of recombinant human endostatin in gastric cancer with malignant ascites. Methods: Clinical data of 90 patients (37 in an Endostar® combined with cisplatin group and 53 in a cisplatin group) were retrospectively analyzed. The primary end point was overall survival, and the secondary end points were objective response rate (ORR), disease control rate (DCR) and so on. Results: Median overall survival was longer in the combination group (9.7 vs 8.1 months; p = 0.01). ORR and DCR were higher in the combination group (ORR: 75.7% vs 54.7%; p = 0.04; DCR: 94.6% vs 75.5%; p = 0.02). There were no significant differences in adverse effects between the two groups. Conclusion: Intraperitoneal administration of recombinant human endostatin improved efficacy and survival for gastric cancer with ascites.

Ascites (a buildup of fluid in the abdomen) resulting from the spread of gastric cancer (GC) results in extremely poor clinical outcomes, and current treatments have shown little effectiveness. Previous results showed that abdominal injection with chemotherapeutic agents enabled an increase in the dose of chemotherapeutic agents and reduced side effects or undesirable effects in the abdominal cavity. This study aimed to investigate the effectiveness and safety of abdominal injection with the anticancer drug recombinant human endostatin in GC with ascites. Clinical data of 90 patients were inspected and analyzed in this study. Thirty-seven patients who received abdominal infusion with both cisplatin (CDDP) and recombinant human endostatin were included in an Endostar^® combined with CDDP group, and 53 patients who received abdominal infusion with CDDP alone were included in a CDDP group. The results showed that median survival time was longer in the combination group than in the CDDP group (9.7 months vs 8.1 months). Besides, therapeutic outcomes, including objective response rate and disease control rate, were better in the combination group. Side effects or undesirable effects were similar in the two groups. To conclude, abdominal injection with recombinant human endostatin improved survival time and therapeutic outcomes for GC patients with ascites.

Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline.

BACKGROUND AND PURPOSE: To investigate the feasibility of level Ib sparing in selected nasopharyngeal carcinoma (NPC) patients during intensity-modulated radiation therapy (IMRT) based on the International Guideline. PATIENTS AND MATERIALS: Patients with histologically-proven NPC who received definitive IMRT at our group were candidates for this analysis. Other eligibility criteria for analysis were designed according to the recommendation of International Guideline for selective coverage of level Ib. Survival outcomes focused on regional recurrence-free survival (RRFS) and level Ib recurrence rate were analyzed. RESULTS: A total of 450 patients were included, 60 of them received level Ib-covering IMRT due to the first three principles of the International Guideline according to our protocol. Of note, patients with level Ib involvement would receive ultrasound guided puncture, only those with positive pathological results would undergo level Ib-covering IMRT. For the remaining 390 patients who only fulfilled the last two criteria and/or level Ib involvement with negative pathological results, level Ib-sparing IMRT was delivered, with a median follow-up time of 112 months (range 6 to 194 months), reported 5- and 10-year RRFS were 95.4% and 92.9%, respectively. Twenty-two patients occurred regional recurrence at censorship (median 44.5 months), only 4(4/390, 1.03%) were recorded as level Ib recurrence. CONCLUSION: Level Ib-sparing IMRT should be safe and feasible for patients who only had level II involvement with ECE, and/or had a MAD of greater than 2 cm in level II, and/or level Ib involvement with negative pathological results. Further well-designed multi-center prospective trials should be conducted.

Re-evaluation of the prognostic significance of retropharyngeal node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

BACKGROUND AND PURPOSE: To investigate the prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy. MATERIALS AND METHODS: Retrospective studies were performed in a total of 1197 patients. We evaluated the incidence of the retropharyngeal node (RPN) metastasis and the characteristics of the metastatic RPN including laterality, size, necrosis, and extranodal neoplastic spread. RESULTS: RPN metastasis occured in 86.3% of patients. The RPN and level II metastasis shared similar survival outcomes. RPN metastasis was an independent prognostic factor for distant failure (hazard ratio = 1.615; 95% confidence interval, 1.063-2.452; P = 0.025), in which the laterality of RPN metastasis significantly influences both the distant failure (P = 0.006) and disease progression (P = 0.001). In N1 disease, the occurrence of unilateral and bilateral RPN metastasis resulted in significantly different outcomes of the disease-specific survival (P = 0.045) and progression-free survival (P = 0.049). The co-occurrence of bilateral RPN and cervical lymph nodes (CLN) metastasis was an independent adverse prognostic factor (P < 0.01) for distant failure and disease progression but not for locoregional recurrence. CONCLUSION: Both the RPN and level II are the first stations of NPC lymph node metastasis. For N1-stage NPC patients, RPN metastasis, especially co-occurrence of bilateral RPN and CLN metastasis, have an adverse influence on survival outcomes.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Primary gross tumor volume is prognostic and suggests treatment in upper esophageal cancer.

BACKGROUND: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. METHODS: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. RESULTS: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. CONCLUSION: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

Percutaneous endoscopic gastrostomy can improve survival outcomes in patients with N3 nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy.

OBJECTIVES: Our previous study revealed that percutaneous endoscopic gastrostomy (PEG) and intensive nutritional support may minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced nasopharyngeal carcinoma (LA-NPC) during concurrent chemoradiotherapy (CCRT). This study aimed to further explore the potential long-term survival benefits of PEG in LA-NPC. METHODS: Between June 1, 2010 and June 30, 2014, a total of 133 consecutive LA-NPC patients who received prophylactic PEG (pPEG) feeding before the initiation of CCRT were included. Meanwhile, an additional 133 non-PEG patients, who were matched for age; sex; and tumor, node, and metastases stage, were selected as control cohort. The log-rank test was used to compare survival distributions between groups. Multivariate prognosis analysis was conducted using a Cox's proportional hazards regression model. RESULTS: After a median follow-up time of 81 months (range: 4-119 months), pPEG was not associated with significant survival benefits in the whole cohort. However, the N3 NPC patients who underwent PEG had significantly higher 5-year overall survival (OS) and progression-free survival (PFS) (84.0 and 76.0%, respectively) than those who did not undergo PEG (56.7 and 45.6%, respectively; p < 0.05). Univariate and multivariate analyses demonstrated that PEG was an independent factor for N3 survival. CONCLUSION: PEG can maintain the nutritional status and improve the rate of treatment completion for LA-NPC patients who underwent CCRT, and these advantages can transfer into survival benefits in N3 NPC. Further multicenter prospective clinical trials are warranted.

Administration of oral maintenance chemotherapy for 1 year following definitive chemoradiotherapy may improve the survival of patients with stage N3 nasopharyngeal carcinoma.

OBJECTIVES: This study aims to evaluate the effectiveness and the optimal maintenance period of oral chemotherapy using S1 following definitive chemoradiotherapy in patients with stage N3 nasopharyngeal carcinoma (N3-NPC). MATERIALS AND METHODS: A retrospective review was performed for N3-NPC treatment with maintenance chemotherapy (MC) [chemoradiotherapy (CRT)-MC] or without MC (CRT-non-MC) following definitive CRT between May 2014 and December 2017. Toxicities during MC were recorded. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared between CRT-MC and CRT-non-MC cohorts. The optimal duration of using maintenance S1 (MC-S1) was also analyzed. RESULTS: A total of 304 patients with stage N3-NPC were identified, of whom 56 were treated with CRT-MC and 248 with CRT-non-MC. After a median follow-up of 48 months, significant differences in OS (74.9 vs. 91.7%; P = 0.003), PFS (60.7 vs. 83.7%; P = 0.001) and DMFS (68.8 vs. 85.5%; P = 0.015) were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leukopenia and fatigue were common but not severe (grade 1-2) side effects of MC. The OS, DMFS and PFS were significantly higher for patients who received S1 administration over a period of ≥12 cycles compared with those who received <12 cycles (3-year OS, 100 vs. 87.5%, P = 0.018; 3-year PFS, 93.9 vs. 67.9%, P = 0.006; 3-year DMFS, 97.1 vs. 67.9%, P = 0.002). CONCLUSIONS: Using MC-S1 in patients with N3-NPC following definitive chemoradiotherapy achieved superior survival rate compared with the patients with non-MC. The side effects of MC-S1 were mild and tolerable. S1 should be maintained for ≥12 cycles.

Modified reduced-volume intensity-modulated radiation therapy in non-metastatic nasopharyngeal carcinoma: A prospective observation series.

BACKGROUND AND PURPOSE: Although the efficacy of "reduced-volume intensity-modulated radiation therapy (IMRT)" in nasopharyngeal carcinoma (NPC) has been confirmed, two issues regarding the necessity of clinical target volume 1(CTV1) delineation and the optimal margin of CTV2 remained undetermined. The current series, utilized de-intensification technique that omitted the contouring of CTV1 and narrowed the margin of CTV2 from 10 mm to 8 mm, namely "modified reduced-volume IMRT" was initiated to evaluate the efficacy and feasibility of this renew technique in a prospective series. PATIENTS AND MATERIALS: Dosimetric analysis was performed in 40 non-metastatic NPC cases to evaluate whether our modification is feasible. Then this de-intensification technique was applied in non-metastatic NPC patients treated in our attending group since late 2014. Survival outcomes focused on local recurrence-free survival (LRFS) and local failure pattern were analyzed. RESULTS: Preliminary dosimetric evaluation of "modified reduced-volume IMRT" showed that the 60 Gy isodose curve generated naturally by this technique could well wrap the target area of CTV1. Subsequent observation series, which included a total of 471 patients and had a median follow-up time of 46.2 months(range,3.7-70.8 months), reported that 4-year estimated LRFS, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.6%, 97.7%, 87.7% and 92.4%, respectively. All local recurrence lesions occurred within 95% isodose lines and were considered in-field failures. CONCLUSIONS: Our de-intensification technique "modified reduced-volume IMRT" was feasible and did not compromise therapeutic efficacy, well-designed multicenter prospective trials are needed for further research.