TPS6137 Background: Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Currently, induction chemotherapy combined with concurrent chemoradiotherapy has become a Category I recommendation for NPC treatment. Studies show that the GP regimen is one of the most effective induction chemotherapy protocols for locally advanced NPC. However, the incidence of grade 3-4 acute toxicities with the GP regimen is as high as 75.7%, severely affecting patient treatment compliance. To reduce toxicity while maintaining efficacy, this study focuses on a "chronomodulated chemotherapy" strategy, which adjusts drug administration timing based on biological rhythms to minimize damage to normal tissues. Methods: Clinical Data: 1. Sample Size Calculation: This study is a randomized controlled trial with a non-inferiority design. Based on a 3-year recurrence-free survival rate of 85.3% in the conventional group, a non-inferiority margin (δ) of 10%, a one-sided α of 0.025, a power (1-β) of 0.8, equal group sizes, and accounting for a 10% dropout rate, the calculated total sample size is 434 subjects. 2. Inclusion Criteria: Treatment-naïve patients with Stage III or IVa non-keratinizing nasopharyngeal carcinoma (UICC/AJCC 8th edition). 3. Exclusion Criteria: History of prior malignancy, prior radiotherapy, or presence of other severe diseases. 4. Withdrawal Criteria: Occurrence of severe adverse events or intolerable toxicities during the study. Treatment Protocol: 1. Induction Chemotherapy Phase: Experimental Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8, administered between 08:00-09:30; Cisplatin 80 mg/m², continuous IV infusion (civ) on day 1, delivered evenly over 12 h from 10:00 to 22:00. Repeated every 3 weeks (Q3W) for 3 cycles. Control Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8; Cisplatin 80 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 cycles. 2. Concurrent Chemoradiotherapy Phase: Concurrent Cisplatin Regimen: Experimental Group: Cisplatin 100 mg/m², civ on day 1, delivered evenly over 12 h from 10:00 to 22:00. Q3W for 3 courses. Control Group: Cisplatin 100 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 courses. 3. Radiotherapy: Intensity-Modulated Radiation Therapy (IMRT) was used, with a total dose of 69.96-72.6 Gy delivered in 33 fractions. Innovation: Therapeutic efficacy for nasopharyngeal carcinoma has reached a plateau, making “toxicity reduction” a key research focus. The toxicity-reducing approach of chronomodulated chemotherapy holds promising application prospects for locally advanced nasopharyngeal carcinoma. Current Status: To date, 122 patients have been enrolled. Clinical trial information: ChiCTR2400086032.
PURPOSE:The efficacy and safety of TPF-induced chemotherapy(IC) combined with concurrent chemoradiotherapy(CCRT) compared to CCRT and sequential PF-adjuvant chemotherapy(AC) lack phase III randomized controlled clinical trials for evaluation, so the comparative efficacy and safety between the two approaches remain unclear. METHODS AND MATERIALS:This randomized clinical phase III trial recruited patients from May 2018 to July 2021,at 4 institutions in China(NCT03574324), 266 patients were enrolled and randomly assigned to either the IC or AC groups. The IC group received TPF followed by CCRT, while the AC group received CCRT followed by PF. We are reporting on the primary outcome of progression-free survival (PFS) and secondary endpoints of overall survival(OS), locoregional relapse-free survival(LRFS), distant metastasis-free survival(DMFS), and toxicity profile. RESULTS:The 3-year PFS was similar between the two groups, with 79 % for the IC group and 74.5 % for the AC group (P = 0.454) at a median follow-up of 39 months. Similar findings were observed, with no significant disparities in OS, LRFS, and DMFS between the two treatment cohorts. Both groups had similar compliance rates for radiotherapy and chemotherapy. However, the IC group experienced fewer grade toxic effects during CCRT, such as nausea/vomiting, swallowing, and dryness (101[77.10 %] vs. 114[89.06 %] patients,40 [30.53 %]vs56 [43.75 %] patients and 58 [44.27 %]vs86 [67.19 %] patients, respectively). However,3-4 grade leukopenia and neutrophilia patients were increased(58 [44.27 %]vs28 [21.88 %] patients and 78 [59.54 %]vs24 [18.75 %]) in the IC group. CONCLUSIONS:In this randomized clinical trial, IC did not improve 3-year PFS for LA-NPC patients and increased hematological toxicity. Still, the advantage of it is that it did reduce the incidence rates of nausea/vomiting, swallowing, and dry mouth during radiotherapy.
e18034 Background: To research whether TPF (Docetaxel plus Fluorouracil plus Cisplatin) chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy can reduce long-term toxicity without affecting the survival of patients with de novo metastatic nasopharyngeal carcinoma (mNPC) compared with conventional chemotherapy combined with cisplatin concurrent chemoradiotherapy. Methods: A retrospective analysis of the clinical data of 121 de novo mNPC patients who treated with TPF chemotherapy at our hospital from January 1, 2012, to December 31, 2018. Among them, 79 patients were treated with chrono-chemotherapy and 42 patients were treated with conventional chemotherapy. The specific chemotherapy regimen for chrono-chemotherapy group:TPF induction chemotherapy for 2-4 cycles, docetaxel: 75mg/m2, ivgtt, d1; Cisplatin: 75mg/m2, civ, d1-5, 60h (10Am—10Pm); 5-Fluorouracil: 750mg/m2/d, civ, administered by intravenous infusion of electronic chemotherapy automatic injection pump d1-5, 60 hours (10 Pm-10 Am), 21 days/cycle. The evaluation of therapeutic efficacy after induction should involve intensity-modulated radiotherapy for at least patients with stable disease, during which concurrent cisplatin chemotherapy is administered. Two cycles of adjuvant chemotherapy were administered 1 month after radiotherapy with the same regimen as induction chemotherapy. The total chemotherapy cycle was 4-6 cycles. The Kaplan-Meier method and log-rank test were used to estimate overall survival (OS) and progression-free survival (PFS), while the COX proportional hazards model was employed for multivariate analysis. Long-term toxic side effects between the two groups were assessed using the chi-square test or Mann-Whitney U test. Propensity score matching was utilized to address confounding factors. Results: At a median follow-up of 104 months, 69.6% of patients died in the chrono-chemotherapy group and 73.8% in the conventional chemotherapy group, and the median OS and PFS in the chrono-chemotherapy group and conventional chemotherapy group were 40 vs 32 months (P=0.636) and 30 vs 19 months, respectively (P=0. 975), there were no statistically significant differences in OS rates and PFS rates at 3, 5, and 7 years between the two groups before and after matching. The incidence of xerostomia, dysphagia, and trismus in the chrono-chemotherapy group matched for timing was significantly lower than that in the conventional chemotherapy group, with a statistically significant difference. (P<0.05). Conclusions: The TPF chrono-chemotherapy combined with cisplatin concurrent chemoradiotherapy reduces the incidence of toxic side effects while ensuring survival, which can benefit patients.
6100 Background: To investigate whether TPF induction chemotherapy combined with concurrent chemoradiotherapy (CCRT) can provide greater survival benefits compared to CCRT followed by PF adjuvant chemotherapy. Methods: Patients with newly diagnosed locally advanced (Stage III–IVA) nasopharyngeal carcinoma (NPC) treated at the Affiliated Tumor Hospital of Guizhou Medical University, the Second Affiliated Hospital of Guizhou Medical University, the Second Affiliated Hospital of Zunyi Medical University, and Guiyang Hospital of Guizhou Aviation from May 2018 to July 2021 were enrolled. Each group included 133 patients. The experimental group received 3 cycles of TPF induction chemotherapy (docetaxel 75mg/m²,intravenous infusion, Day 1; cisplatin 75mg/m²,continuous intravenous infusion over 5 days,10:00–22:00 daily; fluorouracil 750mg/m²/day, continuous intravenous infusion over 5 days, 22:00–10:00 daily) followed by 2–3 cycles of concurrent chemotherapy (cisplatin 100mg/m², continuous intravenous infusion over 2 days, 10:00–22:00 daily). The control group received PF adjuvant chemotherapy (cisplatin 80mg/m², continuous intravenous infusion over 5 days,10:00–22:00 daily; fluorouracil 800mg/m²/day, continuous intravenous infusion over 5 days, 22:00–10:00 daily) combined with 2–3 cycles of concurrent chemotherapy (same as induction chemotherapy).Both groups underwent intensity-modulated radiotherapy (IMRT),with total doses of 69.96 Gy for T1–T2 primary lesions, 72.6 Gy for T3–T4 lesions, and 69.96 Gy for positive lymph nodes. Data were analyzed using SPSS 26.0.Differences in 5-year PFS, OS, LRFS, DMFS, and adverse events were compared between the two groups. Results: No significant differences were observed between the two groups in age, sex, Karnofsky Performance Status (KPS) score, T stage, N stage, or overall stage ( P > 0.05).At a median follow-up of 58 months, the 5-year PFS in both the intention-to-treat and per-protocol populations was similar between the induction chemotherapy (IC) and adjuvant chemotherapy (AC) groups (66.6% vs 66.0%, P = 0.589; 75.3% vs 69.9%, P =0.471). The 5-year OS, LRFS, and DMFS rates were 73.0% vs 71.3% ( P =0.582), 87.4% vs 90.8% ( P =0.508), and 76.9% vs 72.6% ( P =0.267), respectively, with no significant differences. Conclusions: Both groups had similar 5-year PFS, OS, LRFS, DMFS, and long-term toxicity profiles. Clinical trial information: NCT03574324 . 5-year observation indicators for two groups. Observation indicators IC+CCRT CCRT+AC P value Risk ratio(95% CI) PFS ITT Population 66.6% 66.0% 0.589 0.89(0.58-1.36) PP Population 75.3% 69.9% 0.471 0.85(0.55-1.33) OS 73.0% 71.3% 0.582 0.88(0.55-1.39) LRFS 87.4% 90.8% 0.508 1.30(0.60-2.80) DMFS 76.9% 72.6% 0.267 0.75(0.45-1.25) OS, LRFS, and DMFS were all calculated in the ITT population.
e18036 Background: To investigate the dynamic changes of peripheral blood immune-related indicators and their association with therapeutic efficacy in patients with recurrent/metastatic nasopharyngeal carcinoma (NPC) treated with PD-1 inhibitors combined with the GP regimen. Methods: A retrospective analysis was conducted on 46 patients with recurrent/metastatic NPC. All patients received at least one PD-1 antibody inhibitor (camrelizumab/toripalimab/sintilimab/tislelizumab) combined with GP (gemcitabine + cisplatin) chemotherapy. Peripheral blood samples were collected at baseline and after three treatment cycles to measure immune-related indicators, including PD-1, CTLA-4, and Treg cells. The expression differences of these indicators at baseline between the objective response group (PR+CR) and the poor-response group (SD+PD), as well as their dynamic percentage changes during treatment, were compared. Univariate and multivariate logistic regression analyses were further performed to determine whether PD-1, CTLA-4, Treg, CD4+/CD8+ ratio, CD3+, CD4+, CD16+, PDC, and MDC were independent factors influencing treatment efficacy. Results: Baseline peripheral blood PD-1 expression was significantly lower in the objective response group (PR+CR) compared to the poor-response group (SD+PD) (p<0.05). Trends of decrease were observed in Treg, CD16+, CD4+, and CD4+/CD8+ ratio in the objective response group (p>0.05), while trends of increase were noted for CTLA-4, CD3+, MDC, and PDC (p>0.05). After treatment, levels of PD-1 and CD16+ decreased significantly compared to baseline (p<0.05). Although CTLA-4, Treg, CD3+, CD4+, CD4+/CD8+ ratio, MDC, and PDC showed decreasing trends post-treatment, the differences were not statistically significant (p>0.05). Multivariate logistic regression analysis indicated that PD-1 was an independent factor influencing treatment efficacy in patients with recurrent/metastatic NPC (p<0.05). Conclusions: PD-1 inhibitor combined with GP regimen chemotherapy demonstrates favorable efficacy in recurrent/metastatic NPC. Low baseline PD-1 expression may be associated with better therapeutic outcomes. The significant post-treatment decrease in PD-1 and CD16+ expression may suggest immune cell activation and migration to tumor sites following treatment.
Intracranial neuroendocrine carcinoma (NEC) is a highly uncommon malignancy, accounting for approximately 0.74% of cases. It is characterized by rapid infiltration and poor survival rates. This case report details a 51-year-old woman who presented with headaches. Magnetic resonance imaging (MRI) identified an enhancing lesion in the right temporal lobe, and the diagnosis was confirmed by immunohistochemical (IHC) analysis. The patient underwent surgical resection, followed by chemoradiotherapy for recurrence, and subsequent Gamma Knife radiosurgery combined with bevacizumab. Notably, she has achieved a postoperative survival exceeding four years to date. This report comprehensively describes the clinical presentation, diagnostic workup, multidisciplinary treatment course, and favorable outcome, highlighting the potential for prolonged survival with aggressive, multimodal management.
BACKGROUND AND PURPOSE:Radiotherapy (RT) is the most commonly-used treatment for nasopharyngeal carcinoma (NPC). Ferroptosis is a type of regulated cell death that is associated with cancer development. This study aims to investigate the relationship between RT and iron metabolism in NPC patients, as well as the effects of different doses of ionizing radiation (IR) on NPC cells and the role played by ferroptosis METHODS AND MATERIALS: A retrospective analysis was conducted on changes in iron metabolism markers-serum iron, hemoglobin, TIBC, UIBC, and transferrin saturation-before and after radiotherapy in 73 participants. CCK-8 assay was used to assess the effects of varying radiation doses on the viability of 5-8F cells, determining the radiation dose applied in this study. Real-time quantitative PCR (RT-qPCR) was performed to examine how different radiation doses affect the expression of ferroptosis-related genes (FRGs), including ACSL4, ATP5G3, PTGS2, and IREB2. Western blot analysis was employed to measure the protein expression levels of GPX4 under varying radiation doses. The contents of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malonaldehyde (MDA), [Fe2+], adenosine triphosphate (ATP), and glutathione (GSH) were assessed to evaluate the induction of ferroptosis. In addition, flow cytometry was used to analyze cell cycle distribution in NPC cells following various doses of IR. FRGs expression was assessed in NPC cell lines with varying radiosensitivity RESULTS: Compared to pre-radiotherapy levels, serum iron and transferrin saturation significantly increased after treatment, while hemoglobin and UIBC showed marked reductions. The CCK8 results indicated that after exposure to 2-18 Gy of radiation, the viability of 5-8F cells was lowest at a dose of 10 Gy. In irradiated NPC cells, mRNA expression of pro-ferroptosis factors such as ACSL4, PTGS2, and IREB2 was generally upregulated, whereas protein levels of the anti-ferroptosis factor GPX4 were downregulated. As the IR dose increased, the contents of LDH, ROS, and MDA were upregulated, while ATP and GSH levels were downregulated. In addition, high-dose IR exposure can block NPC cells in the G2/M phase. Moreover, we found that the expression levels of three ferroptosis driver genes were lower in radioresistant NPC cell line CONCLUSIONS: High dose IR can induce ferroptosis in NPC cells, highlighting the potential for developing novel ferroptosis-based targets and overcoming radioresistance in clinical NPC treatments.
BACKGROUND AND AIMS:To compare the efficacy and safety of transarterial chemoembolization (TACE) + lenvatinib (TACE+L) versus lenvatinib (L) monotherapy in the treatment of advanced hepatocellular carcinoma by a meta-analysis.METHODS:PubMed, Embase, the Cochrane Library, CNKI, VIP e-Journals Database, and Wanfang Data were systematically searched to collate literature comparing TACE+L with L alone for the treatment of advanced liver cancer. The literature search, quality assessment, and data extraction were performed independently by two reviewers. The Stata 16 software package was used to process and analyze the data. We assessed heterogeneity using both I2 and the p-value, performed a publication bias assessment, and conducted a sensitivity analysis.RESULTS:Five studies were finally included, including one randomized controlled study and four retrospective studies; these involved a total of 1,167 patients, including 523 patients in the TACE+L combination group and 644 patients in the L monotherapy group. In this meta-analysis, the TACE+L group showed a significantly better objective response rate (ORR) (OR=2.54, 95%CI: 1.34 - 4.80) and disease control rate (DCR) compared to the L monotherapy group (OR=2.68, 95%CI: 1.75 - 4.08). The combined group had significantly improved progression-free survival (PFS) (HR=0.47, 95%CI: 0.40 - 0.56) and overall survival (OS) (HR=0.48, 95%CI: 0.39-0.59). In addition, there was no significant difference found in the overall adverse events of any grade between the two groups (OR=1.13, 95%CI: 0.99 - 1.29).CONCLUSIONS:Compared to L alone, TACE+L treatment resulted in better tumor response, better long-term survival, and was accompanied by controllable adverse events.
Objective:To validate the safety and efficacy of chronochemotherapy for locoregionally advanced nasopharyngeal carcinoma(NPC). Methods:Participants for this phase 11 randomized controlled trial were recruited from the Department of Head and Neck Oncology at the Affiliated Cancer Hospital of Guizhou Medical University.Patients enrolled(128 in total,112 in the final analysis)between April 1,2017,and February 28,2018,were randomly divided into the chronochemotherapy and conventional chemotherapy groups.In the chronochemotherapy group,docetaxel was intravenously administered between 3:30 a.m.and 4:30 a.m.on day 1,followed by intravenous administration of cisplatin between 10:00 a.m.and 10:00 p.m.from day 1to day 5.In addition,5-fluorouracil was administered through a continuous intravenous pump between 10:00 p.m.and 10:00 a.m.(2nd day)from day 1 to day 5.In the conventional chemotherapy group,docetaxel(on day 1),cisplatin(on day 2),and 5-fluorouracil(from day 1 to day 5,120 h in total)were administered without time-specific constraints.Both groups underwent intensity-modulated radiation therapy with 6-MV X-rays.The gross target volume(GTV)comprised the nasopharyngeal GTV and cervical lymph node GTV.The primary endpoint was immune function,quantified by measuring den-dritic cell and lymphocyte subsets,whereas the secondary endpoints were therapeutic efficacy and incidence of adverse events.Pearson Chi-square test was applied to compare total events between the groups,Mann-Whitney U test was used to compare the DC subsets and toxicities,and Wilcoxon signed-rank test was used to compare the continuous variables between the two groups. Results:Chronochemotherapy preserved immune function,as evidenced by elevated levels of myeloid dendritic cells(P=0.394)and higher CD4/CD8 ratio(P=0.781).No significant difference in overall response rate,measured as the sum of complete and partial response rates,was observed between the groups(P=0.711).A reduction in the incidence of vomiting(P=0.002),stomatitis(P=0.028),and mucositis(P=0.028)was observed in the chronochemotherapy group.Leukopenia incidence rate was 83.3%and 92.3%in the chro-nochemotherapy and conventional chemotherapy groups,respectively(P=0.232). Conclusions:In patients with locoregionally advanced NPC,the overall response rate of chronochemotherapy is comparable to that of conventional chemotherapy;however,chronochemotherapy shows fewer adverse events.
PurposeThis study aimed to evaluate 5-year outcomes and the late toxicity profile of chrono-chemotherapy with different infusion rates in patients with locally advanced nasopharyngeal carcinoma (NPC).Methods and materialsOur retrospective analysis included 70 patients with locally advanced NPC stages III and IVB (according to the 2010 American Joint Committee on Cancer staging system). Patients were treated with two cycles of induction chemotherapy (IC) before concurrent chemoradiotherapy (CCRT) at Guizhou Cancer Hospital. The IC with docetaxel, cisplatin (DDP) and fluorouracil regimen. Patients were divided into two groups during CCRT. Using a “MELODIE” multi-channel programmed pump, DDP (100 mg/m2) was administered for 12 hours from 10:00 am to 10:00 pm and repeated every 3 weeks for 2-3 cycles. DDP was administered at the peak period of 4:00 pm in the sinusoidal chrono-modulated infusion group (Arm A, n=35). The patients in Arm B received a constant rate of infusion. Both arms received radiotherapy through the same technique and dose fraction. The long-term survival and disease progression were observed.ResultsAfter a median follow-up of 82.8 months, the 5-year progression-free survival rate was 81.3% in Arm A and 79.6% in Arm B (P = 0.85). The 5-year overall survival rate was not significantly different between Arm A and Arm B (79.6% vs 85.3%, P = 0.79). The 5-year distant metastasis-free survival rate was 83.6% in Arm A and 84.6% in Arm B (P = 0.75). The 5-year local recurrence-free survival rate was 88.2% in Arm A and 85.3% in Arm B (P = 0.16). There were no late toxicities of grade 3-4 in either group. Both groups had grade 1-2 late toxicities. Dry mouth was the most common late toxic side effect, followed by hearing loss and difficulty in swallowing. There was no statistically significant difference between Arm A and Arm B in terms of side effects.ConclusionLong-term analysis confirmed that in CCRT, cisplatin administration with sinusoidal chrono-modulated infusion was not superior to the constant infusion rate in terms of long-term toxicity and prognosis.
PURPOSE:This prospective clinical trial aims to compare the efficacy and safety of gemcitabine plus cisplatin (GP) versus docetaxel plus cisplatin and fluorouracil (TPF) as induction chemotherapy combined with locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma (dmNPC). METHODS:146 dmNPC patients were randomly assigned in a 1:1 ratio to receive 4-6 cycles of GP (GP group) or TPF induction chemotherapy (TPF group) followed by locoregional radiotherapy (LRRT). The primary endpoint was overall survival (OS). Secondary endpoints consisted of progression-free survival(PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs). RESULTS:As of data cutoff (May 31, 2024), the median follow-up time was 60.0 months (IQR 40.3-68.1). There is no significant difference in median OS (35.4 vs. 34.8 months, p = 0.2609) and PFS (15.8 vs. 14.3 months, p = 0.2318) between the GP and TPF groups. No significant differences in ORR (65.8 % vs. 71.2 %, p = 0.476) and DCR (79.5 % vs. 82.2 %, p = 0.674) were observed between GP and TPF group too. Furthermore, the 5-year OS was 40.1 % (95 % CI, 29.6 %-54.2 %) in the GP group, compared with 27.2 % (95 % CI, 17.9 %-41.3 %) in the TPF group(HR = 0.79, 95 % CI, 0.53-1.20). However, the TPF group had higher incidences of grade 3-4 AEs such as neutropenia, leukopenia, nausea, and diarrhea. CONCLUSION:The study indicates that 4-6 cycles of TPF induction chemotherapy combined with LRRT achieves a therapeutic effect comparable to the GP regimen with controllable safety.
To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. Median follow-up was 42 months (20–71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3–4 leukocytes and neutrophils, diarrhea, 1–2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6
Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.
Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.
This study was implemented for the evaluation on the circulating endothelial cells’ (CECs) clinical significance in the locally advanced nasopharyngeal carcinoma treatment with endostatin-combined chemoradiotherapy. This study enrolled 47 patients with locally advanced nasopharyngeal carcinoma who were hospitalized from May 9, 2012 to March 10, 2013. These patients were split up into the observation group (25 patients) and control group (22 patients). Patients in the observation group received the endostatin combined with induction chemotherapy and subsequently with concurrent chemoradiotherapy with endostatin. Patients in the control group were treated with inductive chemotherapy followed by concurrent chemoradiotherapy. CECs in peripheral blood were conducted separately before or after inductive chemotherapy and additionally in the end of concurrent chemoradiotherapy. The CEC values of the observation group showed significant statistical differences (p<0.05) before or after different therapies, whereas those data in the control group were not statistically different. And, the mostly importantly, the CEC values in the observation group and control group turned out a statistical difference. The combination of endostatin and chemoradiotherapy significantly reduced parameters of peripheral blood CECs in these patients. According to the CEC parameters’ variety that we observed in the combined therapies, this study demonstrated that the CECs might be a clinical clue to evaluate this antiangiogenic chemoradiotherapy. And the clinical value of CECs will be further determined along with increasing comparative studies and clinical long-term efficacy observation.
Objective:To explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.
目的:探讨复方斑蝥注射液联合放化疗在局部晚期鼻咽癌治疗中的应用价值.方法:以我中心2015年7月至2017年4月收治的157例初治局部晚期鼻咽癌患者为研究对象,将其随机分为试验组79例与对照组78例.试验组患者采用复方斑蝥注射液联合同步放化疗,对照组患者行常规同步放化疗治疗.收集临床资料,比较两组患者治疗期间相关不良反应发生率、机体免疫功能变化和近期疗效情况.结果:试验组与对照组的CR、PR、SD、PD差异无统计学意义(P=0.269>0.05),近期有效率(CR+PR)差异存在统计学意义(P=0.001),试验组较优于对照组;进一步分析两组患者的4级不良反应发生率存在统计学差异(P<0.05),两组患者治疗前后CD3+、CD4+、CD4+/CD8+、CD8+、CD19+淋巴细胞计数下降,试验组较对照组下降趋势缓和.结论:局部晚期鼻咽癌在规范抗肿瘤治疗过程中给予复方斑蝥注射液治疗可降低患者治疗期间严重不良反应的发生率,对机体免疫功能可能有一定的保护作用,并在一定程度上可辅助提高疗效,需开展多中心、大样本临床研究进一步证实.
目的:探索节律基因Per1在咽喉部鳞癌中的表达及与临床病理和预后的相关性.方法:收集2015年10月至2016年9月贵州省肿瘤医院头颈肿瘤科咽喉部鳞癌患者的术后病理标本15例及13例咽喉部活检患者病理标本证实为非肿瘤的正常组织标本,采用RT-qPCR法检测两组标本中Per1 mRNA的表达水平;收集2013年1月至2017年3月60例经病理确诊为咽喉部鳞癌患者的存档蜡块及其中的20例癌旁组织蜡块,同时收集对应患者的临床病理资料,采用免疫组化法检测两组标本中Per1蛋白的表达情况,并分析Per1蛋白表达水平与患者临床病理发展及预后相关性.结果:Per1 mRNA在咽喉部鳞癌组织中的表达水平显著低于咽喉部正常组织中的表达水平(P<0.05),且局部晚期咽喉部鳞癌患者标本中的Per1 mRNA表达水平明显低于早期咽喉部鳞癌患者标本中的表达水平(P<0.05).Per1在咽喉部鳞癌组织中的蛋白表达水平明显低于癌旁组织中的表达水平(P<0.05).通过Kap-lan-Meier统计学分析,Per1蛋白阳性表达组3年总生存率和无进展生存率明显高于阴性组,差异有统计学意义(P<0.05).结论:节律基因Per1在咽喉部鳞癌组织中的表达显著下调,且其表达水平与咽喉部鳞癌患者的生存呈正相关,可能成为咽喉部鳞癌患者预后的重要标志物.
目的 探讨同期放化疗联合诱导或辅助时辰化疗两种治疗局部晚期鼻咽癌模式的疗效和安全性.方法 收集2018年5月至2019年4月72例局部晚期初治鼻咽癌患者进行前瞻性研究,随机分为试验组(n=36)例和对照组(n=36).试验组采用多西他赛、顺铂联合氟尿嘧啶(TPF)方案诱导时辰化疗3个周期(多西他赛75 mg/m2 d1,顺铂75 mg/m2分d1~d5,氟尿嘧啶750 mg/m2/d d1~d5)+3个周期同期放化疗(顺铂100 mg/m2);对照组采用3个周期同期放化疗(顺铂100 mg/m2)+顺铂联合氟尿嘧啶(PF)方案辅助时辰化疗3个周期(顺铂80 mg/m2分d1~d5,氟尿嘧啶800 mg/m2/d d1~d5).两组均采用调强放射治疗,T1、T2期原发灶总剂量69.96Gy,T3、T4期原发灶总剂量72.6Gy,阳性淋巴结69.96Gy.比较两组近期疗效、急性不良反应、免疫指标和生存情况.结果 试验组33例,对照组30例可进行疗效和不良反应评价.试验组获CR 14例,PR 16例,有效率(RR)为90.9%;对照组获CR 15例,PR 12例,RR为90.0%.两组RR的差异无统计学意义(P=0.902).试验组和对照组3年生存率分别为93.6%和95.4%,3年无进展生存率为97.9%和96.5%,3年无远处转移生存率为97.9%和97.8%,3年无局部复发生存率为100.0%和98.7%,差异均无统计学意义(P>0.05).试验组和对照组完成5~6个周期化疗的比例分别为100.0%和83.3%,系统性治疗流程用时分别为(144.83±20.828)天和(205.06±48.95)天,差异均有统计学意义(P<0.05).试验组中性粒细胞减少和腹泻的发生率低于对照组(P<0.05),试验组2~4级口腔黏膜炎的发生率明显低于对照组(P=0.038).在白细胞减少、血红蛋白减少、血小板减少、转氨酶升高、恶心呕吐及放射性皮炎等方面,两组无显著差异(P>0.05).试验组和对照组治疗前后CD3+、CD4+、CD8+、CD19+、CD16+CD56+T细胞及CD4+/CD8+水平的差异均无统计学意义(P>0.05).结论 TPF方案诱导时辰化疗联合同期放化疗的治疗模式下,患者依从性好,口腔黏膜炎发生率低,疗效与PF方案辅助时辰化疗联合同期放化疗相当,故对局部晚期初治鼻咽癌推荐诱导时辰化疗联合同期放化疗的治疗模式.
Objective To compare the adverse events, immune status, and short-term efficacy between chronomodulated chemotherapy ( CCR) and routine chemotherapy ( RCR) combined with intensity modulated radiotherapy ( IMRT ) in the treatment of patients with locally advanced nasopharyngeal carcinoma. Methods A total of 159 patients with newly diagnosed locally advanced nasopharyngeal carcinoma were randomized into the CCR group and the RCR group to evaluate the short-term efficacy and adverse events. Results No significant difference was found in CR, PR, SD, and PD between the CCR group and the RCR group ( P>0. 05 ) , and no significant difference was observed in the response rate (CR+PR) between the two groups (P>0. 05). The incidence of leukopenia (Z=-2. 222, P<0. 05), neutropenia ( Z=-1. 999, P<0. 05 ) , vomiting ( Z=-2. 298, P<0. 05 ) , and oral mucositis ( Z=-3. 571, P<0. 05) of the CCR group was lower than those of the RCR group with statistical significance. The CD16+56+ lymphocyte cell count was higher in the CCR group than that in the RCR group ( Z=-2. 332, P<0. 05 ) . Conclusions As a novel invention, CCR combined with IMRT can reduce the incidence and severity of treatment-related adverse events and improve immune status without diminishing clinical efficacy, therefore deserving clinical application.