Locally Advanced Nasopharyngeal Carcinoma Patients Research Articles

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study

Background and PurposeTo investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC).MethodsA total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated.ResultsThe median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively.ConclusionsPatients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients

IntroductionThis retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). Material &MethodsORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. ResultsThe incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. ConclusionAn affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients.

We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by the malignant transformation of nasopharyngeal epithelial cells. It is highly sensitive to radiation therapy, making radiotherapy the primary treatment modality. However, 60-80% of patients are initially diagnosed with locally advanced NPC (LA-NPC), where radiotherapy alone often fails to achieve desirable outcomes. Therefore, combining radiotherapy with chemotherapy has emerged as an effective strategy to optimize treatment for LA-NPC patients. Among the various chemotherapy regimens, concurrent chemoradiotherapy (CCRT) using platinum-based drugs has been established as the most commonly utilized approach for LA-NPC patients. The extensive utilization of platinum drugs in clinical settings underscores their therapeutic potential and emphasizes ongoing efforts in the development of novel platinum-based complexes for anticancer therapy. The aim of this review is to elucidate the remarkable advances made in the field of platinum-based therapies for nasopharyngeal carcinoma, emphasizing their transformative impact on patient prognosis.

Valero’s host index is useful in predicting radiation-induced trismus and osteoradionecrosis of the jaw risks in locally advanced nasopharyngeal carcinoma patients

BackgroundIn the absence of previous research, we sought to assess the H-Index’s predictive significance for radiation-induced trismus (RIT) and osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT).Patients and methodsThe research comprised 295 LA-NPC patients who had C-CRT and pre- and post-C-CRT oral exams between June 2010 and December 2021. The H-Index was calculated using neutrophils, monocytes, lymphocytes, hemoglobin, and albumin measurements obtained on the first day of C-CRT. Patients were divided into three and two H-index groups, respectively, based on previously established cutoff values (1.5 and 3.5) and the cutoff value determined by our receiver operating characteristic (ROC) curve analysis. The primary objective was the presence of any significant connections between pretreatment H-Index groups and post-C-CRT RIT and ORNJ rates.ResultsRIT and ORNJ was diagnosed in 46 (15.6%) and 13 (7.8%) patients, respectively. The original H-Index grouping could only categorize RIT and ORNJ risks at a cutoff value of 3.5, with no significant differences in RIT and ORNJ rates between groups with H-Index 1.5 and 1.5 to 3.5 (P < 0.05 for each). The ideal H-Index cutoff for both RIT and ORNJ rates was found to be 5.5 in ROC curve analysis, which divided the entire research population into two groups: H-Index ≤ 5.5 (N = 195) and H-Index > 5.5 (N = 110). Intergroup comparisons revealed that patients in the H-Index > 5.5 group had significantly higher rates of either RIT (31.8% vs. 5.9%; P < 0.001) or ORNJ (17.3% vs. 2.2%; P < 0.001) than their H-Index ≤ 5.5 counterparts. The results of the multivariate analysis showed that H-Index > 5.5 was independently linked to significantly higher RIT (P < 0.001) and ORNJ (P < 0.001) rates.ConclusionPre-C-CRT H-Index > 5.5 is associated with significantly increased RIT and ORNJ rates in LA-NPC patients receiving definitive C-CRT.

Low hemoglobin levels predict increased radiation-induced trismus rates in nasopharyngeal cancer.

To investigate the predictive significance of hemoglobin (Hb) values in the incidence of radiation-induced trismus (RIT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients who received concurrent chemoradiotherapy (C-CRT). Data of LA-NPC patients were examined before and after C-CRT and to confirm the presence of RIT, maximum mouth openings (MMO) were measured; RIT is defined as an MMO of ≤35 mm. All Hb values were derived from complete blood count tests obtained on the first day of C-CRT. The receiver operating characteristic (ROC) curve analysis was used to scrutinize a possible connection between pre-treatment Hb values and RIT status. Two hundred and twenty three patients were included in the study and RIT was diagnosed in 46 (20.6%) patients. The Hb cutoff in ROC curve analysis that separated the patients into two groups was 12.05 g/dL [Area under the curve (AUC): 82.7%; sensitivity: 72.9%; and specificity: 71.3%]. RIT was significantly more prevalent in the Hb ≤ 12 g/dL group than in its counterpart (41.9% vs. 7.3%; p < 0.001). In multivariate analysis, Hb ≤ 12, anemia, pre-C-CRT MMO < 41.4 mm, and masticatory apparatus doseV58 Gy < 32% groups were found to be independently associated with significantly increased rates of RIT. Low pre-C-CRT Hb and anemia status are novel biological markers that independently predict higher RIT rates in LA-NPC undergoing C-CRT.

The predictive value of pretreatment hemoglobin-to-platelet ratio on osteoradionecrosis incidence rates of locally advanced nasopharyngeal cancer patients managed with concurrent chemoradiotherapy

BackgroundThis retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors.ResultsWe distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months.ConclusionLow pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

Assessment of Response to Different Induction Chemotherapy Regimens in Locally Advanced Nasopharyngeal Carcinoma.

To compare the short-term treatment response and survival of the three induction chemotherapy (IC) regimens, including gemcitabine and cisplatin (GP), docetaxel and cisplatin (TP), and docetaxel, cisplatin, and fluoropyrimidines (TPF) in locally advanced nasopharyngeal carcinoma (LANPC). We included stage III-IVA NPC patients who received ≥3 cycles of IC in this study. The chi-square test, multivariate logistic regression analysis, and Kaplan-Meier method were used for statistical analysis. A total of 227 patients were included. The overall response rate (ORR) of the primary nasopharyngeal tumors after IC with GP, TP, and TPF was 91.9%, 83.8%, and 91.7%, respectively (P=0.729), and the ORR of the cervical lymph nodes was 94.6%, 72.3%, and 85.0%, respectively (P<0.001). For the primary nasopharyngeal tumor, there was no significant difference in the ORR among the three IC regimens. For cervical lymph nodes, patients treated with GP had significantly higher ORR compared to those treated with the TP regimen (P=0.014), and comparable ORR was found between TPF and GP regimens (P=0.161). Similar progression-free survival (PFS) (P=0.501) and overall survival (OS) (P=0.504) were found among three IC regimens. There were comparable PFS (P=0.123) and OS (P=0.478) among those with complete response (CR), partial response (PR), and stable disease (SD)/progressive disease (PD) in the primary nasopharyngeal tumors. However, patients who had CR in the primary nasopharyngeal tumor (P=0.014) and the cervical lymph nodes (P=0.022) had better PFS compared to those who had PR or SD/PD. GP and TPF regimens are equivalent to the TP regimen in the response to primary nasopharyngeal tumors after IC, but with better ORR in the cervical lymph nodes than the TP regimen. The response to IC may be a powerful indicator for predicting prognosis and developing individualized follow-up and treatment strategies for LANPC patients.

Radiation dose escalation for locally advanced nasopharyngeal carcinoma patients with local and/or regional residual lesions after standard chemoradiotherapy: a non-randomized, observational study

BackgroundTo assess the effectiveness and toxicity of radiation dose escalation for locally advanced nasopharyngeal carcinoma (LA-NPC) in patients with local and/or regional residual lesion(s) after standard treatment.MethodsFrom November 2011 to November 2020, 259 LA-NPC patients who had local and/or regional residual lesion(s) after induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) from our hospital were included. The total dose of primary radiotherapy (RT) was 68.1–74.25 Gy (median, 70.4 Gy). The boost doses were 4.0–18.0 Gy (median, 9 Gy), 1.8–2.0 Gy/fraction.ResultsFor all patients, the 5-year local relapse-free survival was 90.2%, regional relapse-free survival was 89.1%, locoregional relapse-free survival (LRRFS) was 79.5%, distant metastasis-free survival (DMFS) was 87.9%, failure-free survival (FFS) was 69.0%, and overall survival (OS) was 86.3%. LRRFS, DMFS, FFS, and OS in patients with age ≤ 65 versus > 65, plasma Epstein-Barr virus-deoxyribonucleic acid ≤ 500 versus > 500, T1–2 versus T3–4, N0–1 versus N2–3, and stage III versus stage IV showed no statistically significant differences. The interval between primary RT and boost was not a prognostic factor for LRRFS, DMFS, FFS, and OS. Males had a lower 3-year FFS rate than females (72.9% vs. 83.7%, P = 0.024). LA-NPCs with locally and regionally residual lesion(s) had the worst 3-year DMFS and OS rates compared with locally or regionally residual lesion(s) (77.7% vs. 98.8% vs. 87.4%, P = 0.014; 75.9% vs. 94.5% vs. 82.4%, P = 0.002).ConclusionBoost radiation was an option for LA-NPCs with locally and/or regionally residual lesions after receiving IC + CCRT. It warrants further prospective study.Trial registration: Retrospectively registered.

Epstein-Barr virus DNA change level combined with tumor volume reduction ratio after inductive chemotherapy as a better prognostic predictor in locally advanced nasopharyngeal carcinoma.

To explore the prognosis predicting ability of the combined factors, Epstein-Barr virus DNA change level (EBVCL) and tumor volume reduction ratio (TVRR) after inductive chemotherapy (IC), in locally advanced nasopharyngeal carcinoma (LANPC). From 2010 to 2018, 299 LANPC patients were included in this retrospective study. Receiver operating characteristic (ROC) curve analysis was performed to acquire the best critical values. According to the best critical values of EBVCL and TVRR, patients were stratified into low- and high-risk groups. Kaplan-Meier and ROC curve analyses were utilized to verify the prognostic ability of the new predictor (EBVCL+TVRR). The prognostic values among EBVCL+TVRR, EBVCL, TVRR, TNM stage, and the RECIST 1.1 criteria were compared by ROC curve. The primary end points were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional failure-free survival (LRFFS). ROC curve analyses of TVRR on three-year survival showed the best critical values of TVRR was 32.72% for OS, 30.21% for PFS and LRFFS, 29.87% for DMFS. The best critical value of EBVCL was 127 copies/ml for OS, and 87.7 copies/ml for PFS, DMFS, and LRFFS. The three-year OS, PFS, DMFS, and LRFFS for low- and high-risk groups were 97.7% versus 78.3% (hazard ratio [HR]=0.2398; 95% confidence interval [CI]: 0.1277-0.4502; p < 0.0001), 91.1% versus 60.9% (HR=0.3294; 95% CI: 0.2050-0.5292; p < 0.0001), 94.2% versus 68.7% (HR=0.2413; 95% CI: 0.1284-0.4535; p < 0.0001) and 97.8% versus 77.9% (HR=0.3078; 95% CI: 0.1700-0.5573; p=0.0001), respectively. The maximal area under ROC curve of EBVCL+TVRR, EBVCL, TVRR, TNM stage, and RECIST 1.1 criteria for three-year OS was 0.829, 0.750, 0.711, 0.555, and 0.605, respectively. The new-developed indicator (EBVCL+TVRR) could better predict the LANPC patient's survival after IC compared with TNM stage system or RECIST 1.1 criteria.

The Effects of Different Induction Chemotherapy Cycles and Adjuvant Chemotherapy on the Survival Outcomes of Patients With Locally Advanced Nasopharyngeal Carcinoma

ObjectiveThis study investigated whether differences in the induction chemotherapy (IC) cycle number and adjuvant chemotherapy (AC) affect survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsThe survival outcomes of 386 consecutive LA-NPC patients treated between January 2015 and March 2018 were retrospectively analyzed. Univariate and multivariate analyses were used to compare treatment groups defined by IC< 3 or ≥3 IC cycles followed by radiotherapy with or without AC (i.e., IC<3+AC, IC<3+non-AC, IC≥3+AC, and IC≥3+non-AC groups).ResultsThe median follow-up time was 53 months (range: 2-74 months) and the median number of IC cycles was 2 (range: 1-6 cycles). The 3-year overall survival (OS) rate was significantly higher in patients with IC≥3 cycles compared to IC<3 cycles (95.7% vs. 90.3%, P=0.020). Multivariate analysis indicated that the IC cycle number is an independent factor for OS (hazard ratio=0.326, P=0.007). Furthermore, patients in the IC<3+AC group had a better OS rate than those in the IC<3+non-AC group (91.6% vs. 79.1%, P=0.030), indicating that AC positively affected OS in patients with IC<3. However, no significant difference in the OS rate was found between IC≥3+non-AC and IC≥3+AC groups (92.1% vs. 94.6%, P =0.550).ConclusionThe IC cycle number appears to be an independent prognostic factor for higher OS in LA-NPC patients who received ≥3 cycles. Sequential AC after IC plus radiotherapy may improve OS in patients with IC<3 cycles.

Predicting Bone Metastasis Risk Based on Skull Base Invasion in Locally Advanced Nasopharyngeal Carcinoma

ObjectiveTo develop and validate a bone metastasis prediction model based on skull base invasion (SBI) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsThis retrospective cohort study enrolled 290 patients with LA-NPC who received intensity-modulated radiation therapy in two hospitals from 2010 to 2020. Patient characteristics were grouped by SBI and hospital. Both unadjusted and multivariate-adjusted models were used to determine bone metastasis risk based on SBI status. Subgroup analysis was performed to investigate heterogeneity using a forest graph. Cox proportional hazard regression analysis was used to screen for risk factors of bone metastasis-free survival (BMFS). A nomogram of BMFS based on SBI was developed and validated using C-index, receiver operating characteristic curve, calibration curves, and decision curve analysis after Cox proportional hazard regression analysis.ResultsThe incidence of bone metastasis was 14.83% (43/290), 20.69% (24/116), and 10.92% (19/174) in the overall population, SBI-positive group, and SBI-negative group, respectively. In the unadjusted model, SBI was associated with reduced BMFS [HR 2.43 (1.32–4.47), P = 0.004], and the results remained stable after three continuous adjustments (P <0.05). No significant interaction was found in the subgroup analyses (P for interaction >0.05). According to Cox proportional hazard regression analysis and clinical value results, potential risk factors included SBI, Karnofsky performance status, TNM stage, induction chemotherapy, concurrent chemoradiotherapy, and adjuvant chemotherapy. Using a training C-index of 0.80 and a validation C-index of 0.79, the nomogram predicted BMFS and demonstrated satisfactory prognostic capability in 2, 3, and 5 years (area under curve: 83.7% vs. 79.6%, 81.7% vs. 88.2%, and 79.0% vs. 93.8%, respectively).ConclusionSkull base invasion is a risk factor for bone metastasis in patients with LA-NPC. The SBI-based nomogram model can be used to predict bone metastasis and may assist in identifying LA-NPC patients at the highest risk of bone metastasis.

The Prognostic Impact of Combined Tumor-Infiltrating Lymphocytes and Pretreatment Blood Lymphocyte Percentage in Locally Advanced Nasopharyngeal Carcinoma.

PurposeTo explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and MethodsTILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs–LYM% score = 0), middle-risk group (MRG) (TILs–LYM% score = 1), and low-risk group (LRG) (TILs–LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs–LYM% status with clinicopathological factors and survival, were evaluated.ResultsAs a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan–Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs–LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs–LYM% score was an independent factor affecting survival of the patients, and HRG (TILs–LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs–LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs–LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone.ConclusionsA positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs–LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.

Predictive Value of Ki-67 for Neoadjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> To assess the predictive value of Ki-67 expression for adjuvant chemotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). <h3>Materials/Methods</h3> The authors retrospectively evaluated 1374 patients with stage III-IVa nasopharyngeal carcinoma in Sichuan Cancer Hospital from 2013 to 2019, of which 638 patients received induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT), and 736 patients received concurrent chemoradiotherapy (CCRT) alone. Clinical and pathological features of the patients with LA-NPC were retrieved from the hospital records. Follow-up was measured from the first day of therapy to last examination or death. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and Metastasis-free survival (MFS). The ROC curve was carried out to analyze the Ki-67 cut off value related to OS. According to the cut off value of Ki-67, LA-NPC patients was divided into two groups. The efficacy of neoadjuvant chemotherapy was analysis in the two groups respectively. The OS, PFS, LRFS and MFS rates were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazard models were used to evaluate independent risk factors for OS, PFS, MFS and LRFS. <h3>Results</h3> The median (interquartile range) follow-up time was (42.3 months [10.3-62.4]). The level of Ki-67 expression was not significantly correlated with age, gender, T stage, N stage, or histological type. The ROC curve showed that the Ki-67 cut off value related to OS was 50%. Among the LA-NPC patients with higher Ki-67 expression (>50%), we observed a significant difference between IC+CCRT group and CCRT group, including 3-years OS (96.7% vs 75.5%, <i>P</i> = 0.011), PFS (81.7% vs 66.7%, <i>P</i> = 0.007), LRFS (88.9% vs 94.1%, <i>P</i> = 0.530), and MFS (91.9% vs 66.7%, <i>P</i> = 0.003). However, among the LA-NPC patients with lower Ki-67 expression (≤50%), there was no significant difference between IC+CCRT group and CCRT group, including 3-years OS (91.1% vs 80.4%, <i>P</i> = 0.631), PFS (80.9% vs 85.2%, <i>P</i> = 0.921), LRFS (91.6% vs 96.7%, <i>P</i> = 0.312), and MFS (84.0% vs 85.2%, <i>P</i> = 0.913). <h3>Conclusion</h3> We found that LA-NPC patients got survival benefit from neoadjuvant chemotherapy may depend on the expression of Ki-67. LA-NPC patients with higher expression of Ki-67 (> 50%) can have a better survival outcome after neoadjuvant chemotherapy. The expression level of Ki-67 was a potential marker for predicting the efficacy of neoadjuvant chemotherapy in LA-NPC.

Low-Dose Ultra-Fractionated Radiotherapy as a Chemosensitizer of Neoadjuvant Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma: A Preliminary Results of the Phase II Trial

The main failure model of locally advanced nasopharyngeal carcinoma (LANPC) is local failure and distant metastasis. N stage is a prognostic factor for NPC. Some characteristics of lymph nodes, such as the size, number, laterality, extra-nodal neoplastic spread and central necrosis, were the high-risk factors for treatment failure. Nowadays, neoadjuvant chemotherapy followed with concurrent chemo radiotherapy was recommended for LANPC patients. Low-dose radiotherapy (LDRT), which is < 100 cGy, induces enhanced cell killing in vitro and in vivo by the hyper-radiation sensitivity phenomenon and potentiates effects of chemotherapy. Few studies reported about it. Recently, a single arm study showed it could improve the ORR to 82% for head and neck squamous carcinoma when combined with neoadjuvant chemotherapy. So, we aimed to investigate the efficacy of LDRT combined with neoadjuvant chemotherapy for high-risk LANPC.Squamous III-IVA NPC patients (UICC/AJCC 8th) with high-risk factors of lymph nodes were prospectively enrolled in the study. The high-risk factors should include one of these followings: lymph node with central necrosis, extranodal neoplastic spread, contrast-enhancing rim or the shortest diameter of lymph nodes ≥3cm. 3 cycles of neoadjuvant chemotherapy were given, the regimen was docetaxel (75mg/m2 D1) and cisplatin (75mg/m2 D1). LDRT was delivered as 50 cGy per fraction twice a day for gross nodal disease on D1 and D2 of neoadjuvant chemotherapy. All the patients received MRI scan before and after the neoadjuvant chemotherapy. Propensity score matching was used to select the patients as control group. RECIST criteria was used to evaluate the ORR.From Jun 2020 to Jan 2021, a total of 27 patients were enrolled in the study. Another 27 patients were matched for control group. For the whole patients, the median age were 43 years. III and IVA Clinical stage were 25.9%, 74.1% and 29.6%, 70.4% respectively for LDRT and control group (P = 0.761). As for the lymph nodes, the ORR of LDRT group was significantly higher than control group (100% vs 85.2%, P = 0.038). The average regression rate of lymph nodes was 89.4% in LDRT group, CR and PR was 7.4% and 92.6%. However, the average regression rate of it was only 56.24% in control group. There was no CR, PR and SD were 88.9% and 11.1%. For the primary tumor, there was no significant difference. But we found the ORR of it was higher in LDRT group (96.3% vs 81.5%, P = 0.083). And the average regression rate was 57.5% and 38.3% respectively in LDRT and control group.LDRT combined with neoadjuvant chemotherapy could improve the ORR for primary tumor and lymph nodes in high-risk LANPC patients, especially for lymph nodes. This new treatment model could be a promising strategy to improve local control, and needed to be confirmed in the future practice.

Comparison of therapeutic efficacy and toxicity of docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy plus concurrent chemoradiotherapy and chemoradiotherapy alone in locally advanced nasopharyngeal carcinoma.

Purpose:In recent years, docetaxel, cisplatin, and fluorouracil (TPF)-based induction chemotherapy plus concurrent chemoradiotherapy (CCRT) has been commonly applied for locally advanced nasopharyngeal carcinoma (LA-NPC). However, whether TPF+CCRT regimen is the best choice for LA-NPC remains unclear. This meta-analysis aims to elucidate and compare the efficacy and toxicity of TPF+CCRT versus CCRT alone for LA-NPC.Methods:Two investigators independently and systematically searched relevant studies available on PubMed, Embase, Cochrane Library, and Web of Science published before January 7, 2021. Data were extracted from eligible studies for assessing their qualities, and calculating pooled hazard ratios (HR), odds ratio (OR) and 95% confidence intervals (CI) using Review Manager software 5.3 (RevMan 5.3).Results:Five studies involving 759 LA-NPC patients were analyzed in the meta-analysis. Compared to CCRT alone, TPF-based IC plus CCRT significantly improved overall survival (OS) (HR = 0.53, 95% CI: 0.35–0.81, P = .003), progression-free survival (PFS) (HR = 0.63, 95% CI: 0.46–0.86, P = .004), distant metastasis-free survival (DMFS) (HR = 0.58, 95% CI: 0.39–0.86, P = .008), and locoregional failure-free survival (LRFFS) (HR 0.62, 95% CI: 0.43–0.90, P = .01). In addition, TPF-based IC plus CCRT mainly increased risks of grade 3/4 acute hematological toxicity and non-hematological toxicities like leukopenia (OR = 1.84, 95% CI: 0.42–8.03, P = .42), neutropenia (OR = 1.78, 95% CI: 0.23–13.82, P = .58), thrombocytopenia (OR = 1.76, 95% CI: 0.53–5.81, P = .35), febrile neutropenia (OR = 2.76, 95% CI: 0.07–101.89, P = .58), vomiting (OR = 18.94, 95% CI: 0.99–362.02, P = .05) and dry mouth (OR = 2.23, 95% CI: 0.22–22.57, P = .50), which were uncomplicated and manageable.Conclusions:TPF + CCRT is superb than CCRT alone for the management of LA-NPC. However, TPF+CCRT increases the incidences of grade 3/4 acute hematological toxicity and some non-hematological toxicities.

Early Efficacy Prediction of Nasopharyngeal Carcinoma Based on 3D-ADC Acquired During Radiotherapy: A Phase II Prospective Study

Concurrent chemoradiotherapy (CCRT) is the main treatment model for locally advanced nasopharyngeal carcinoma (LANPC). Previous study found the apparent diffusion coefficient (ADC) value of primary tumor partly correlated to prognosis for NPC patients. Recent studies reported that the changes of ADC value at pre- and post-treatment was a more sensitive predictor for prognosis. The prognosis for LANPC patients who received the same treatment strategy varies greatly. The early predictor was urgently needed to help for adjusting the treatment strategy. Thus, we aimed to observe the dynamic changes of ADC of gross target volume (GTV) and metastatic lymph nodes (LN) for NPC patients during radiotherapy (RT), and explored the potential correlations between ADC changes and treatment response.A total of 50 squamous NPC (II-IVa, the 8th TNM staging system) patients treated with CCRT were enrolled in this study. All patients received a planned total dose of 66 to 70Gy in 33 fractions at 5 fractions per week using Image-guided intensity modulated radiotherapy (IGRT). The regimen was cisplatin-based chemotherapy for 3 cycles. The patients received diffusion weighted MRI (DWI) scan at pre-RT, the 5th and 15th fractions and immediately post-RT on a 3.0T MRI system (b = 0, 500, 800s/mm2) system. The ADC values of GTV and LN were acquired using a commercially available software. RECIST1.1 criteria was used to evaluate the tumor response. Multivariate analyses were calculated using the logistic regression model. Receiver-operating characteristic (ROC) curve was used to determine the cut-off value of ADC.After the completion of CCRT, the ORR for all the patients was 100% (CR 58%, PR 42%). The mean ADC value of GTV and LN gradually increased from pre-RT to post RT. These changes generally occurred in two stages. For the first stage (from pre-RT to the 5th fraction), the mean ADC value of GTV and LN increased significantly by 20.78% and 22.96% respectively, while the volumes of GTV and LN had minimal changes (GTV:18.42cm3 vs 16.72cm3, LN: 4.67cm3 vs 4.12cm3). As for the second stage (from the 5th fraction to post-RT), the mean ADC value of GTV and LN continued to increase by 45.58% and 41.2% respectively, while the volumes decreased by 86.07% (GTV) and 61.6% (LN). Multivariate analysis showed the mean ADC changes of GTV from pre-RT to the 5th fraction (ΔADC5) was the only independent prognostic factor for treatment response of NPC. ROC showed that the cut-off value for ΔADC5 was 158.82mm2/s (sensitivity:87%; specificity:65%).Mean ADC values of GTV and LN increased dramatically during RT for NPC patients treated with radiotherapy. The mean ADC began to increase at the 5th fraction, while the change of volume was minimal. Early ADC changes at the 5th fraction might be a new and sensitive biomarker to predict the prognosis for NPC patients independently of volume change.

Comparison of TPF and TP Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma Based on TNM Stage and Pretreatment Systemic Immune-Inflammation Index.

PurposeTo evaluate the efficacy and toxicity of the two IC (induction chemotherapy) regimens, TPF (taxanes, cisplatin, and 5-fluorouracil) and TP (taxanes and cisplatin) combined with concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients.MethodsUltimately, we enrolled 213 patients at stage III-IVA in this retrospective study. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The toxicities were evaluated according to CTCAE v4.0 and RTOG criteria.ResultsTPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients. The optimal value of pretreatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with SII ≥432.48 showed superior OS (P=0.038) and DMFS (P=0.028) from TPF. Also, SII was proved to be a prognostic element for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032) in multivariate analysis, and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3–4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048), diarrhea (P=0.036), and ear damage (P=0.046) were more common in TPF group.ConclusionOur study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while for stage III and N0-1, TP might be ample. In high-risk LA-NPC patients (stage IVA combined with pretreatment SII ≥432.48), TPF had a higher 5-year OS and DMFS, with more grade 3–4 toxicities, but most of them were endurable.

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

ObjectivesOur 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. MethodsBetween 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. ResultsAfter 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. ConclusionPEG 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.

High Pretreatment Platelet-to-Albumin Ratio Predicts Poor Survival Results in Locally Advanced Nasopharyngeal Cancers Treated with Chemoradiotherapy.

PurposeIn a lack of similar research, we assessed the prognostic utility of pretreatment platelet-to-albumin ratio (PAR) in locally advanced nasopharyngeal carcinoma (LANPC) patients managed with concurrent chemoradiotherapy (CCRT).Patients and MethodsPresent retrospective analysis included a sum of 128 consecutively treated LANPC patients who underwent cisplatinum-based radical CCRT. Availability of an ideal pretreatment PAR cutoff that may stratify the study population into two cohorts with significantly distinct survival outcomes was sought by utilizing the receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively.ResultsA rounded 5.2 [area under the curve (AUC): 68.9%; sensitivity: 67.4%; and specificity: 65.2%] value was identified as the ideal PAR cutoff that grouped patients into two gatherings [PAR≥5.2 (N=60) versus <5.2 (N=68)]. The median follow-up duration was 86.4 months (range: 9–147). Kaplan–Meier comparisons between the two PAR groups revealed significantly diminished median PFS (69.4 versus 106.8 months for PAR<5.2; P< 0.012) and OS (88.3 versus not reached yet for PAR<5.2; P= 0.023) for the PAR ≥ 5.2 group. The results of multivariate analyses affirmed the pretreatment PAR≥5.2 as an independent prognostic factor that indicates diminished PFS (P= 0.016) and OS (P= 0.019) together with the respective N2-3 nodal stage (versus N0-1; P<0.05 for PFS and OS, respectively) and weight loss >5% at past six months (≤5%; P<0.05 for PFS and OS, respectively).ConclusionThe results of the current retrospective analysis provided a robust and independent adverse prognostic value for pretreatment PAR ≥ 5.2 in terms of median and long-term PFS and OS outcomes in LA-NPC patients this patient group treated with conclusive CCRT.