Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making

objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.

Clinical Effect of Biafine in Preventing and Treating Radioactive Skin Destruction of Nasopharyngeal Carcinoma Patients Caused by Concurrent Intensity- Modulated Radiotherapy and Chemotherapy

OBJECTIVE To observe the clinical effect of Biafine cream in preventing and treating radioactive skin destruction of nasopharyngeal carcinoma （NPC） patients induced by synchronized intensity-modulated radiotherapy and chemotherapy. METHODS The patients were treated with Varian-600CD 6 MV X-ray three-dimensional （3D） conformal intensity-modulation radiotherapy （IMRT）, with a 120-blade multiple leaf-blade grating and in combination with synchronal Capecitabine chemotherapy. Fifty-one patients undergoing radiotherapy and chemotherapy were randomized into 2 groups： 25 in the treatment group received a Biafine cream application following the first radiotherapy and / or chemotherapy, while the other 26, served as controls. They received no application of the cream, but only followed normal procedures for conventional radiotherapy and health education. RESULTS The rate of the skin-reaction was 100% in the patients of both groups. A mild radiation reaction （grade-Ⅰ and Ⅱ） occurred as follows： 88.0% （22/25 cases） in the treatment group and 57.7% （15/26 cases） in the control group. A grade-Ⅲ radiation reaction developed in 12.0% （3/25 cases） in the treatment group, and 42.3% （11/26 cases） in the controls. There was a significant difference, P〈0.01 between the two groups. Concerning the degree of the skin response before the patients received a dose of 40 Gy, the radiation reaction emerged in 32.0% （8/25） of the cases in the treatment group, and in 96.2% （25/26） of the cases of the control group. CONCLUSION Biafine cream can effectively reduce the acute irradiation or chemotherapy-induced dermal injury. It can alleviate the patients＇ suffering, improve their quality of life, and can ensure less injurious radiotherapy.

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

Background:To protect neurological tissues,underdosing occurs in most cases of T4 nasopharyngeal carcinoma(NPC) with intracranial extension.In this study,we aimed to evaluate the effect of dosimetric inadequacy on local control and late neurological toxicities for patients treated with intensity-modulated radiotherapy(IMRT) plus chemotherapy.Methods:We prospectively enrolled patients who had non-metastaticT4 NPC with intracranial extension treated between January 2009 and November 2013.The prescribed dose was 66.0-70.4 Gy to the primary planning target volume(primary gross tumor volume [GTVp;i.e.,the nasopharyngeal tumor] +5.0 mm).Dose-volume histogram parameters were calculated,including minimum point dose(D_(min)) and dose to 95% of the target volume(D95).All patients received chemotherapy with the cisplatin,5-fluorouracil,and docetaxel regimen.Survivals were estimated using the Kaplan-Meier method and compared using the log-rank test.Results:In total,41 patients were enrolled.The local partial response rate was 87.8% after induction chemotherapy.With a median follow-up of 51 months,7 patients experienced failure in the nasopharynx;the 3-year local failure-free survival and overall survival rates of the 41 patients were 87.4% and 90.2%,respectively.The actual mean D_(min) to the GTVp was 55.2 Gy(range 48.3-67.3 Gy),and D95 was 61.6 Gy(range 52.6-69.0 Gy).All doses received by neurological organs remained well within their dose constraints.No patients developed temporal lobe necrosis or other neurological dysfunctions.Conclusions:With relative underdosed IMRT plus effective chemotherapy,the patients achieved satisfactory local control with few late toxicities of the central nervous system.Determining the acceptable extent of dosimetric inadequacy requires further exploration.

Comparative Study between Patients Treated with Conventional Radiotherapy and IMRT with Chemotherapy for Stage III - IVA Nasopharyngeal Carcinoma: A Single Institution Retrospective Report

Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ2 = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.

The clinical effects of concurrent radiochemotherapy in cases suffered from stages III to IVa nasopharyngeal carcinoma

Objective： The aim of the study was to investigate the clinical effects of concurrent radiochemotherapy in treating locally advanced （Stages III-IVa） nasopharyngeal carcinomas （NPCs）. Methods： A total of 95 patients who suffered from nasopharyngeal carcinoma （Stages III-IVa） was divided into two groups： Group concurrent radiochemotherapy （Group CCRT, n = 49） and Group radiotherapy （Group RT, n = 46）. The two groups were both delivered conventional fractionated radiotherapy, while Group CCRT was delivered three cycles chemotherapy of PF （DDP ＋ 5-Fu） regimen or PLF （DDP ＋ 5-Fu ＋ CF） regimen. Results： The complete remission rate and total remission rate of Group CCRT were higher than those of Group RT, and the differences were of statistical importance （X2 = 4.72-7.19, P 〈 0.05）. The one-year overall survival （OS） rate was calculated by life table method, in Group CCRT, it was higher than that of Group RT and the difference was of statistical importance （X2 = 4.24, P 〈 0.05）. The 3-year overall survival （OS） rate, nasopharyngeal control rate and cervical lymph nodes＇ control rate of Group CCRT were all higher than those of Group RT and the differences were of statistical importance （X2 = 4.28-4.40, P 〈 0.05）. The 5-year overall survival （OS） rate and metastasis-free rate of Group CCRT were higher than those of Group RT and the differences were of statistical importance （X2 = 3.96-8.26, P 〈 0.05）. The incidence rates of acute toxicities in Group CCRT were obviously higher than those in Group RT, and the difference of gastrointestinal reaction was of statistical importance （X2 = 11.70, P 〈 0.05）. Conclusion： This study has demonstrated that concurrent radiochemotherapy can improve the remission rate, overall survival rate and locally control rate. The toxicities of concurrent radiochemotherapy can be tolerated by the patients.

Clinical Observation of Concurrent Radio-Chemotherapy Combined with Adjuvant Chemotherapy in Treating Locoregionally Advanced Nasopharyngeal Carcinoma

OBJECTIVE To investigate the efficacy and side effects of concurrent radiochemotherapy using the TP regimen （paclitaxel and cisplatin） combined with adjuvant treatment in treating patients with locoregionally advanced nasopharyngeal carcinoma （NPC）. METHODS A total of 82 patients with a confirmed diagnosis of locoregionally advanced stage-III and IVa NPC were randomly divided into 2 groups： the treatment group （TG） with concurrent radiochemotherapy combined with adjuvant chemotherapy （n = 44） and the control group （CG） with simple radiotherapy （RT） （n = 38）. A total dose of 68 - 74 Gy of conformal radiation （X-ray, 4 MV or 8 MV） was given to patients in both groups. In the TG, a regimen of paxlitaxel and cisplatin was given via intravenous infusion in the 1st and 6th week concurrently with RT. After a 2-week intermission following RT, these patients received 2 cycles of the same chemotherapeutic regimen triweekly. RESULTS The effective rates of the treatment were, respectively, 71.1% and 76.3% in the CG, and 88.6% and 95.5% in the TG, at the end of treatment and 3 months thereafter. The differences in the therapeutic efficacy between the 2 groups were statistically significant （P 〈 0.05）. The 1- and 2-year survival rates were 81.1% and 73%, and 95.2% and 90.5%, respectively in the CG and the TG, and the differences between the 2 groups were statistically significant （P 〈 0.05）. The grade I-II reactions in the gastrointestinal tract, skin and oral mucosa were higher in patients receiving concurrent radiochemotherapy combined with adjuvant chemotherapy than in patients receiving simple radiotherapy （P 〈 0.05）. The differences in the occurrence of grade III-IV side effects including gastrointestinal, dermal and oral mucosal discomfort, other side effects, and late radioactive damage between the 2 groups were not statistically significant. CONCLUSION Concurrent radiochemotherapy combined with adjuvant chemotherapy in treating patients with locoregionally advanced NPC can further improve short-term therapeutic effects and the overall survival. However, there is an increased trend in toxicity secondary to treatment.

Cycle number of neoadjuvant chemotherapy might influence survival of patients with T1-4N2-3M0 nasopharyngeal carcinoma

Objective： Stage N2-3 nasopharyngeal carcinoma（NPC） shows a high risk of distant metastasis, which will finally cause death. This study aimed to evaluate the impact of neoadjuvant chemotherapy（NACT） of various cycles before radical radiotherapy on distant metastasis and survival of patients with stage N2-3 diseases.Methods： In this study, a total of 1,164 consecutive patients with non-metastatic N2-3 NPC were recruited and prospectively observed. Then 231 patients who received NACT of 4 cycles（NACT=4 group） were matched 1：2：1 to 462 patients treated with NACT of 2 cycles（NACT=2 group） and 231 patients treated without NACT（NACT=0 group）, according to age, histological subtype, N stage and NACT regimen. Five candidate variables（sex, T stage, concurrent chemotherapy, intensity-modulated radiation therapy and cycle number of NACT） were analyzed for their association with patients＇ survival.Results： After matching, the overall survival（OS）, disease-free survival（DFS）, local-recurrence-free survival（RFS） and distant-metastasis-free survival（MFS） of the NACT=4 group（89.2%, 81.0%, 83.3% and 84.8%,respectively） were better than those of the NACT=2 group（83.3%, 72.5%, 81.2% and 77.9%, respectively） and the NACT=0 group（74.0%, 63.2%, 74.0% and 68.8%, respectively）. In multivariate analysis, the cycle number of NACT maintained statistical significance on the OS, DFS, RFS and MFS（all P〈0.05）.Conclusions： For N2-3 NPC, cycle number of NACT appeared to be an independent factor associated with an improvement of survival.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma

The value of adding induction chemotherapy(IC) to concurrent chemoradiotherapy(CCRT) for the treatment of locoregionally advanced nasopharyngeal carcinoma(NPC) remains unclear.In our recent article entitled "Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma:a phase 3,multicentre,randomised controlled trial" published in the Lancet Oncology,we reported the results of a phase Ⅲ,multicenter,randomized controlled trial comparing cisplatin,5-fluorouracil,and docetaxel(TPF) IC plus CCRT versus CCRT alone in patients wit hT3-4N1/TxN2-3M0 NPC(Clinical Trials.gov registration number NCT01245959).The IC-plus-CCRT group showed significantly higher 3-year failure-free survival,overall survival,and distant failure-free survival rates than the CCRT-alone group,with an acceptable toxicity profile.Our study suggests that adding TPF IC to CCRT could increase survival rates and reduce distant failure in patients with locoregionally advanced NPC.However,long-term follow-up is required to assess the eventual efficacy and toxicity of this strategy,and a more accurate method to determine prognosis is needed to enable better tailoring of treatment strategy for individual patients.

PhaseⅡstudy of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma

Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.

Predictive value of tumor volume reduction rates before and after induction chemotherapy in determining the radiosensitivity and prognosis of locally advanced nasopharyngeal carcinomas

Objective This study investigated the predictive value of tumor volume reduction rates(TVRRs) before and after induction chemotherapy in determining the radiosensitivity and prognosis of patients with locally advanced nasopharyngeal carcinomas(NPCs). Methods The clinical data of 172 patients with locally advanced primary NPCs who were treated from January 2009 to December 2012 were collected. Tumor regression was evaluated based on the results of the computed tomography scan or magnetic resonance imaging studies. Data about the tumor diameters before and after induction chemotherapy and after radiotherapy as well as the survival times of the patients were obtained. Results All 172 patients had NPCs. After radiotherapy, the TVRR in patients without residual tumor cells was higher than that in patients with residual tumor cells after induction chemotherapy(median values: 47.7% and 15.1%, respectively), and the 5-year survival rates were 80.3% and 45.6%, respectively. Neck lymph node metastasis was observed in 161 of 172 patients, and the TVRRs were similar(median values: 46.8% in 161 patients without residual tumor cells and 11.1% in 161 patients with residual tumor cells). The 5-year survival rate of the 161 patients without residual tumor cells was 84.5%, and that of patients with residual tumor cells was 37.3%. As shown by the receiver operating characteristic(ROC) curve, the area under the curve(AUC) of the ROC curve for TVRRs in patients with primary NPCs but without residual tumors was 0.851, whereas that for TVRRs in patients with neck lymph node metastasis but without residual tumors was 0.784. This result indicates that TVRR has a high diagnostic performance. The univariate Cox regression analysis showed that clinical stage, TVRR in primary NPCs, neck lymph node metastatic lesions before and after induction chemotherapy, presence or absence of residual tumor cells in primary NPCs, and neck lymph node metastatic lesions after radiotherapy were significantly correlated to overall survival(OS). Results of the multivariate Cox regression analysis showed that clinical stage and presence or absence of residual tumor cells in the lymph nodes after radiotherapy were the independent prognostic factors of OS.Conclusion The TVRR after induction chemotherapy may be an effective predictive indicator of the treatment efficacy of radiotherapy in patients with NPC.

INTERVENTION CHEMOTHERAPY IN COMPREHENSIVE TREATMENT OF ADVANCED NASOPHARYNGEAL CARCINOMA

Objective: To study the use of interventional chemotherapy in comprehensive treatment for advanced nasopharyngeal carcinoma. Methods: Interventional chemotherapy with multi-drugs including cisplatin (DDP) 100 mg, 5-fluorouracil (5-FU) 1000 mg and bleomycin (BLM) 16 mg was used to treat 30 cases with advanced nasopharyngeal carcinoma before radiotherapy. 50 cases that received radiotherapy alone were used as a control group. The methods, time and dose schedule of radiotherapy were similar in the two groups. Results: The primary lesions in 16 cases and the cervical lymph nodes in 12 cases were reduced hi size after interventional chemotherapy. Radiation doses of those in complete response in their primary lesion and cervical lymph nodes were lower than that of the control group (P<0.05). The complete response rate of study group was 83.3% and that of control group was 72.0% (P<0.05). Conclusion: Interventional chemotherapy plus radiotherapy is a valuable treatment method in advanced nasopharyngeal carcinoma.

Neoadjuvant chemotherapy plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy plus adjuvant chemotherapy for the treatment of locoregionally advanced nasopharyngeal carcinoma:a retrospective controlled study

Background:In the era of intensity-modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NAC)for locoregionally advanced nasopharyngeal carcinoma(NPC)is under-evaluated.The aim of this study was to compare the efficacy of NAC plus IMRT and concurrent chemoradiotherapy(CCRT)plus adjuvant chemotherapy(AC)on locoregionally advanced NPC.Methods:Between January 2004 and December 2008,240 cases of locoregionally advanced NPC confirmed by pathologic assessment in Sun Yat-sen University Cancer Center were reviewed.Of the 240 patients,117 received NAC followed by IMRT,and 123 were treated with CCRT plus AC.The NAC+IMRT group received a regimen that included cisplatin and 5-fluorouracil(5-FU).The CCRT+AC group received cisplatin concurrently with radiotherapy,and subsequently received adjuvant cisplatin and 5-FU.The survival rates were assessed by Kaplan-Meier analysis,and the survival curves were compared using a log-rank test.Multivariate analysis was conducted using the Cox proportional hazard regression model.Results:The 5-year overall survival(OS),locoregional relapse-free survival(LRRFS),distant metastasis-free survival(DMFS),and disease-free survival(DFS)were 78.0,87.9,79.0,and 69.8%,respectively,for the NAC+IMRT group and78.7,84.8,76.2,and 65.6%,respectively,for the CCRT+AC group.There were no significant differences in survival between the two groups.In multivariate analysis,age(<50 years vs.>50 years)and overall stage(Ⅲvs.Ⅳ)were found to be independent predictors for OS and DFS;furthermore,the overall stage was a significant prognostic factor for DMFS.Compared with the CCRT+AC protocol,the NAC+IMRT protocol significantly reduced the occurrence rates of grade 3-4 nausea-vomiting(6.5 vs.1.5%,P=0.023)and leukopenia(9.7 vs.0.8%,P=0.006).Conclusions:The treatment outcomes of the NAC+IMRT and CCRT+AC groups were similar.Distant metastasis remained the predominant mode of treatment failure.

Role of chemotherapy in stage Ⅱb nasopharyngeal carcinoma

The efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy on stage Ⅱb nasopharyngeal carcinoma (NPC) remains unclear. Conventional two-dimensional radiotherapy combined with concurrent chemotherapy can improve the overall survival, progression-free survival, recurrence-free survival, and distant metastasis-free survival of patients with stage Ⅱb NPC. Intensity-modulated radiotherapy without concurrent chemotherapy also provides good outcomes for patients with stage Ⅱb NPC. This article summarizes the features of stage Ⅱb NPC and reviews the role of chemotherapy in this subgroup of NPC.

Colonic perforation in a nasopharyngeal carcinoma patient treated with fluorouracil: A case report

BACKGROUND Nasopharyngeal carcinoma(NPC)is a commonly encountered type of tumor.Fluorouracil(FU)is an effective treatment providing satisfactory oncologic outcomes in nasopharyngeal carcinoma patients.We describe a unique case of colonic perforation in an NPC patient treated with FU.Thus far,only two cases of intestinal perforation associated with FU treatment have been reported.We hope that the analysis of the relationship between the adverse effects of FU and physiological factors will help to reduce the incidence of colonic perforation in patients with nasopharyngeal carcinoma treated with FU.CASE SUMMARY A 67-year-old female patient suffered from NPC stage pT3N2M0.She had a history of three surgical procedures:Partial enterectomy,partial sigmoidectomy,and sigmoidostomy.After the administration of 2.75 g FU,a bloody stool appeared and the patient developed abdominal pain.Subsequent examination indicated colitis and intestinal perforation.CONCLUSION FU is a commonly used drug in NPC chemotherapy.The most common adverse effect of FU is gastrointestinal reaction,and the colonic perforation found here is thought to be caused by gastrointestinal mucosal injury consequential to the FU treatment.When selecting chemotherapy drugs,their side effects and the physical condition of patients should be considered,particularly in patients with a history of gastrointestinal surgery.

Comparison of Volumetric and Dosimetric Variations in Nasopharyngeal Carcinoma during Intensity-modulated Radiation Therapy with and without Neoadjuvant Chemotherapy

Objective Patients with nasopharyngeal carcinoma(NPC)undergoing intensity-modulated radiation therapy(IMRT)may experience significant volumetric and dosimetric variations throughout the treatment course.However,neoadjuvant chemotherapy may reduce the extent of these variations.This study was carried out to evaluate volumetric and dosimetric changes in target volumes and organs at risk(OARs)during IMRT in patients with locally advanced NPC who received concurrent chemoradiotherapy(CCRT)alone or in combination with neoadjuvant chemotherapy(NACT).Methods 35 NPC patients were recruited for this study and divided into the NACT(n=15)and CCRT(n=20)groups.Computed tomography(CT)scans were performed before neoadjuvant chemotherapy,before IMRT,before the 24 th fraction of IMRT,and after treatment.The original plan(plan 0)was based on CT images collected before IMRT.Hybrid plan 1(plan 1)and hybrid plan 2(plan 2)were generated by applying the beam configurations of plan0 to the CT scans collected before the 24 th fraction of IMRT and after treatment.Volumetric and dosimetric variations were assessed by comparing the results of plan 0 with those of plan 1 and plan 2.Results In the NACT group,compared with that in plan 0,the primary gross tumor volume(GTVnx)decreased by 33.2%±18.4%and 50.5%±12.6%in plan1 and plan 2,respectively.In the CCRT group,the corresponding reduction rates in plan 1 and plan 2 were 49.4%±8.0%and 77.8%±28.1%,respectively.The volume decrease rates in the NACT group were less than those in the CCRT group(P<0.001).In the NACT group,compared with that of plan0,the dose to 95%of the volume(D95)for the planning target volume of the primary tumor(PTVnx)decreased by 1.0%±0.7%and 0.6%±0.6%in plan 1 and plan 2,respectively.In the CCRT group,the corresponding decrease rates in plan 1 and plan 2 were 4.2%±3.8%and 6.1%±6.3%,respectively.The decrease rate of D95 for PTVnx in the NACT group was less than that in the CCRT group(P<0.001).Similar results among the plans were found in terms of D99,Dmean,V93 for PTVnxand PTVnd,and Dmeanfor the parotid glands.Conclusion Neoadjuvant chemotherapy reduces the extent of volumetric and dosimetric variations in target volumes and OARs during IMRT and,thus,helps achieve better target volume coverage,protects adjacent important structures,and minimizes unnecessary replanning during radiotherapy.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival(OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio(HR)=0.9, P=0.529]; this risk was 60% lower than that of the group undergoing supportive treatment(HR=0.4, P=0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy(HR=2.3, P<0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

Effect of induction chemotherapy with cisplatin, fluorouracil, with or without taxane on locoregionally advanced nasopharyngeal carcinoma: a retrospective, propensity score-matched analysis

Background:Available data in the literature comparing different induction chemotherapy(IC)regimens on locoregionally advanced nasopharyngeal carcinoma(NPC)are scarce.The purpose of the present study was to evaluate the outcomes of locoregionally advanced NPC patients who were treated with taxane,cisplatin and 5-fluorouracil(TPF)or cisplatin and 5-fluorouracil(PF)as IC followed by concurrent chemoradiotherapy(CCRT).Methods:In total,1879 patients with locoregionally advanced NPC treated with IC and CCRT from a prospectively maintained database were included in the present observational study.We compared overall survival(OS),disease-specific survival(DSS),distant metastasis-free survival(DMFS),and locoregional relapse-free survival,using the pro-pensity score method.Results:In total,1256 patients received TPF or PF as IC backbone.The TPF group showed significantly better OS(hazard ratio[HR],0.660;95%confidence interval[CI]0.442-0.986;P=0.042),DSS(HR,0.624;95%CI 0.411-0.947;P=0.027)and DMFS(HR,0.589;95%CI 0.406-0.855;P=0.005)compared with the PF group in multivariable analy-ses.Propensity score matching identified 294 patients in each cohort and confirmed that TPF was associated with significantly improved 5-year OS(88.1%vs.80.7%;P=0.042),DSS(88.5%vs.80.7%;P=0.021)and DMFS(87.9%vs.78.6%;P=0.012)rates compared with the PF group.There were no significant differences in locoregional relapse-free survival before or after matching.Conclusions:In our study,IC with the TPF regimen combined with CCRT showed improved long-term survival for the patients with locoregionally advanced NPC compared with the PF regimen.However,a prospective randomized clinical trial to validate these findings is necessary.

A Prospective Study on Therapeutic Gain by Concurrent Chemoradiotherapy for Stage Ⅱ-Ⅳa Nasopharyngeal Carcinoma

The benefit achieved by concurrent chemoradiotherapy（CCR） and sequential chemoradiotherapy（SCR） vs radiotherapy（RT） alone for patients with stage Ⅱ-Ⅳa nasopharyngeal carcinoma（NPC） was compared.A total of 113 patients with stage Ⅱ-Ⅳa NPC were allotted into CCR group（n=38）,SCR group（n=36） and RT alone group（n=39）.All patients were irradiated with the same RT technique to ≥66 Gy at 2 Gy per fraction,conventional 5 fractions/week in all groups.The CCR group received concurrent chemotherapy of weekly cisplatin for 7 weeks,and the SCR group received neoadjuvant and（or） adjuvant chemotherapy.The results showed that the 3-and 5-year overall survival rate was significantly higher in CCR group than in RT alone group（92.16% vs 61.54%,81.58% vs 51.28%,P〈0.005）.The median survival time was significantly longer in CCR group than in RT alone group（67.8 months vs 52.7 months,P〈0.005）.It was concluded that CCR could significantly improve overall survival rate,progression-free survival rate,and median survival time when compared with RT alone.

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas

AIM:To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma(NPC).METHODS:We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy(CCRT)(22/40 patients)or CCRT alone(18/40)from March 2006 to March 2012.Patients underwent fiberoscopy with biopsy of the primitive tumor,and computed tomography scan of head,neck,chest and abdomen with and without contrast.Cisplatin was used both as induction and as concomitant chemotherapy,while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions(total dose,70 Gy).The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly.This retrospective analysis was approved by the review boards of the participating institutions.Patients gave their consent to treatment and to anonymous analysis of clinical data.RESULTS:Thirty-three patients were males and 7 were females.Median follow-up time was 58 mo(range,1-92 mo).In the sub-group of twenty patients with a follow-up time longer than 36 mo,the 3-year survival and disease free survival rates were 85%and 75%,respectively.Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%.Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients.Grade 2 mucositis was seen in 29 patients,while grade 2 xerostomia was seen in 30 patients.Overall toxicity was manageable and it did not cause any significant treatment delay.In the whole sample population,long term toxicity included grade 2 xerostomia in 22 patients,grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients.CONCLUSION:Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC.The role of adjuvant chemotherapy remains to be defined.