Denosumab combined with immunotherapy,radiotherapy,and granulocyte-macrophage colony-stimulating factor for the treatment of metastatic nasopharyngeal carcinoma:A case report

BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.

Stage IV malignant transformation of mature cystic teratoma palliatively treated with concurrent chemoradiotherapy:A case report

BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our hospital.Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass.Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell carci-noma.The patient was diagnosed with MT of MCT.Due to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse effects.After CCRT,her performance status improved,and the tumor size was reduced;surgery was performed.Five months postoperatively,the patient developed dis-semination and lymph node metastases.Palliative chemotherapy was ineffective.She died 18 months after treatment initiation.CONCLUSION EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.

Hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma:A case report

BACKGROUND Liver cancer treatment is characterized by multidisciplinary participation and coexistence of multiple treatment methods.Hypofractionated and intensity-modulated radiotherapy is a new precise radiotherapy technique applied to the treatment of systemic malignant tumors.There is a lack of understanding of hypofractionated and intensity-modulated radiotherapy combined with systemic therapy in metastatic hepatocellular carcinoma(HCC).CASE SUMMARY We report a case of metastatic HCC treated with hypofractionated and intensity-modulated radiotherapy combined with systemic therapy.A 41-year-old man was diagnosed with metastatic HCC(T3N1M1 stage IVB).Because it was found to be in the late stage of cancer and had already metastasized,it was impossible to undergo surgical treatment.In addition to aggressive comprehensive treatment for the primary lesion,local treatment for metastatic cancer can improve the patient's survival potential.Hypofractionated and intensity-modulated radiotherapy can provide a larger single treatment dose within a shorter overall treatment time,and improve the local control rate of the tumor.Follow-up examination demonstrated that the tumor and metastatic lesions had shrunk after therapy.The treatment has showed good efficacy.The patient survived for 18 months without disease progression and stable disease persisted for>38 months.CONCLUSION Targeted therapy and immunotherapy followed by hypofractionated and intensity-modulated radiotherapy are also effective for advanced metastatic HCC.

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.

Nedaplatin concurrent with three-dimensional conformal radiotherapy for treatment of locally advanced esophageal carcinoma

AIM:To evaluate the efficacy and toxicity of nedaplatin(NDP)concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma.METHODS:Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group(n=34)or a cisplatin(DDP)group(n=34).The NDP group received NDP 80-100 mg/m2iv on day 1+leucovorin(CF)100 mg/m2iv on days 1-5+5-fluorouracil(5-FU)500 mg/m2iv on days 1-5.The DDP group received DDP 30 mg/m2iv on days 1-3+CF 100 mg/m2on days 1-5+5-FU 500 mg/m2iv on days 1-5.The treatment was repeated every 4 wk in both groups.Concurrent radiotherapy[60-66 Gy/(30-33f)/(6-7 wk)]was given during chemotherapy.RESULTS:There was no significant difference in the short-term response rate between the NDP group and DDP group(90.9%vs 81.3%,P=0.528).Although the 1-and 2-year survival rates were higher in the NDP group than in the DDP group(75.8%vs 68.8%,57.6%vs 50.0%),the difference in the overall survival rate was not statistically significant between the two groups(P=0.540).The incidences of nausea,vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group(17.6%vs 50.0%,P=0.031;11.8%vs 47.1%,P=0.016;8.8%vs 38.2%,P=0.039).There was no significant difference in the incidence of myelosuppression,radiation-induced esophagitis or radiation-induced pneumonia between the two groups.CONCLUSION:NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma.NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3.

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.

Role of radiotherapy in the management of hepatocellular carcinoma:A systematic review

Many patients with hepatocellular carcinoma(HCC) present with advanced disease,not amenable to curative therapies such as surgery,transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization(TACE) and radiation therapy. Especially TACE,delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy,has given favorable results on local control and survival. Radiotherapy,as a therapeutic modality of internal radiation therapy with radioisotopes,has also achieved efficacious tumor control in advanced disease. On the contrary,the role of external beam radiotherapy for HCC has been limited in the past,due to the low tolerance of surrounding normal liver parenchyma. However,technological innovations in the field of radiotherapy treatment planning and delivery,have provided the means of delivering radical doses to the tumor,while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy,evaluated for efficacy and safety for HCC,report encouraging results. In this review,we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment.

3D conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM: To compare transcatheter arterial chemoembolization (TACE) and 3D conformal radiotherapy (3D-CRT) with TACE monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched all the eligible studies from the Cochrane Library, PubMed, Medline, Embase, and CNKI. The meta-analysis was performed to assess the survival benefit, tumor response, and the decline in alpha-fetoprotein (AFP) level. According to the heterogeneity of the studies, pooled OR with 95% CI were calculated using the fixed-effects or random-effects model. An observed OR > 1 indicated that the addition of 3D-CRT to TACE offered survival benefits to patients that could be considered statistically significant. Statistical analyses were performed using Review Manager Software. RESULTS: Ten studies met the criteria to perform a meta-analysis including 908 HCC participants, with 400 patients in the TACE/3D-CRT combination group and 508 in the TACE alone group. TACE combined with 3D-CRT significantly improved 1-, 2- and 3-year overall survival compared with TACE monotherapy (OR = 1.87, 95% CI: 1.37-2.55, P < 0.0001), (OR = 2.38, 95% CI: 1.78-3.17, P < 0.00001) and (OR = 2.97, 95% CI: 2.10-4.21, P < 0.00001). In addition, TACE plus 3DCRT was associated with a higher tumor response (complete remission and partial remission) (OR = 3.81; 95% CI: 2.70-5.37; P < 0.00001), and decline rates of AFP level (OR = 3.24, 95% CI: 2.09-5.02, P < 0.00001). CONCLUSION: This meta-analysis demonstrated that TACE combined with 3D-CRT was better than TACE monotherapy for patients with HCC, which needs to be confirmed by large multicenter trials. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Prognostic value of plasma Epstein-Barr virus DNA level during posttreatment follow-up in the patients with nasopharyngeal carcinoma having undergone intensity-modulated radiotherapy

Background: The value of Epstein-Barr virus(EBV) DNA assay during posttreatment follow-up of the patients with nasopharyngeal carcinoma(NPC) presenting with different pretreatment plasma EBV DNA levels remains unclear. In the present study, we aimed to evaluate the prognostic value of plasma EBV DNA assay during posttreatment followup in the patients with NPC who have undergone intensity-modulated radiotherapy.Methods: The medical records of 385 NPC patients treated with intensity-modulated radiotherapy between November 2009 and February 2012 were reviewed. All patients underwent plasma EBV DNA assays before treatment, within3 months after treatment, and then every 3-12 months during posttreatment follow-up period. The recurrence rates for patients with different pretreatment and posttreatment follow-up plasma EBV DNA levels were analyzed.Results: Of the 385 patients, 267(69.4%) had detectable pretreatment plasma EBV DNA(> 0 copy/mL) and 93(24.2%) had detectable posttreatment EBV DNA during a median follow-up of 52.8 months(range 9.3-73.8 months).Detectable EBV DNA during posttreatment follow-up was found in 14.4%(17/118) and 28.5%(76/267) of patients with undetectable and detectable pretreatment EBV DNA, respectively, and was significantly associated with tumor recurrence in both patient groups. EBV DNA was detectable in 12.8%(40/313) of patients who remained disease-free,56.4%(22/39) of patients with locoregional recurrence alone, and 93.9%(31/33) of patients with distant metastasis as the first recurrence event(P < 0.001); 6.5%(19/292) of patients with undetectable EBV DNA and 57.0%(53/93) of patient with detectable EBV DNA during posttreatment follow-up experienced tumor recurrence. Compared with other cut-off values, the cut-off value of 0 copy/mL for EBV DNA during posttreatment follow-up had the highest area under the ROC curve(AUC) value(0.804,95% confidence interval 0.741-0.868) for predicting tumor recurrence(sensitivity, specificity, and accuracy: 73.6%, 87.2%, and 84.7%, respectively).Conclusion: Plasma EBV DNA level during posttreatment follow-up is a good marker for predicting distant metastasis but not locoregional recurrence in the patients with NPC irrespective of the pretreatment EBV DNA levels.

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.

Concurrent chemoradiotherapy combined with enteral nutrition support:a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant istulae

Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.

Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes;therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyteassociated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment.

Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients have already lost the best surgical timing when diagnosed.Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically,but the efficacy and prognosis of patients from them are still unsatisfactory.Therefore,it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy,and other 45 healthy people during the same period were enrolled as a control group.The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed.The receiver operating characteristic(ROC)curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients,the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients,and the Cox regression analysis to identify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P<0.01).The area under the ROC curve(AUC)of plasma miR-21 for diagnosing T stage,N stage,M stage,and pathological differentiation of ESCC was 0.819,0.758,0.824,and 0.725,respectively,and that of plasma miR-93 for diagnosing T stage,N stage,and M stage of ESCC was 0.827,0.815,and 0.814,respectively.The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894,and the AUCs of them for predicting the 3-year overall survival(OS)were 0.861 and 0.807,respectively.T stage(P<0.05),M stage(P<0.05),miR-21(P<0.01),and miR-93(P<0.05)were independent risk factors for radiotherapy and chemotherapy efficacy,and T stage(P<0.01),N stage(P<0.05),M stage(P<0.01),miR-21(P<0.01),and miR-93(P<0.01)were independent prognostic factors for ESCC patients.CONCLUSION MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients.

Prognostic value and predictive threshold of tumor volume for patients with locally advanced nasopharyngeal carcinoma receiving intensity-modulated radiotherapy

Background: Gross target volume of primary tumor(GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma(NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy(IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ind a suitable cut?of value of GTV?P for prognosis prediction.Methods: Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic(ROC) curves were used to identify the cut?of values of GTV?P for the prediction of diferent end?points [overall survival(OS), local relapse?free survival(LRFS), distant metastasis?free survival(DMFS), and disease?free survival(DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system.Results: The 358 patients with locally advanced NPC were divided into two groups by the cut?of value of GTV?P as determined using ROC curves: 219(61.2%) patients with GTV?P ≤46.4 mL and 139(38.8%) with GTV?P >46.4 mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P ≤46.4 mL than in those with GTV?P > 46.4 mL(all P < 0.05). Multivariate analysis indicated that GTV?P >46.4 mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriied that the predictive ability of GTV?P was superior to that of T category(P < 0.001). The cut?of values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4 mL, respectively.Conclusion: In patients with locally advanced NPC, GTV?P >46.4 mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.

A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients

Background:For patients with nasopharyngeal carcinoma(NPC) who undergo re-irradiation with intensity-modulated radiotherapy(IMRT),lethal nasopharyngeal necrosis(LNN) is a severe late adverse event.The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC.Methods:Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study.Clinical characteristics,including recurrent carcinoma conditions and dosimetric features,were evaluated as candidate risk factors for LNN.Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model.Results:Among 228 patients enrolled in this study,204 were at risk of developing LNN based on risk analysis.Of the 204 patients treated,31(15.2%) developed LNN.Logistic regression analysis showed that female sex(P = 0.008),necrosis before re-irradiation(P = 0.008),accumulated total prescription dose to the gross tumor volume(GTV) ≥ 145.5 Gy(P = 0.043),and recurrent tumor volume >25.38 cm3(P = 0.009) were independent risk factors for LNN.A model to predict LNN was then constructed that included these four independent risk factors.Conclusions:A model that includes sex,necrosis before re-irradiation,accumulated total prescription dose to GTV,and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Radiation-induced osteosarcoma of the maxilla and mandible after radiotherapy for nasopharyngeal carcinoma

Background:The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible(RIOSM) has become a significant problem that can limit long-term survival.The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma(NPC).Methods:We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012.Of these patients,47 who developed RISOM and met inclusion criteria were included in this study.Two of these 47 patients refused treatment and were then excluded.Results:For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period,the total incidence of RIOSM after radiotherapy was 0.084%(47/53,760).Two patients(4.4%) had metastases at the diagnosis of RIOSM.Thirty-nine of the 45(86.7%) patients underwent surgery for RIOSM;most patients(24/39;61.5%) who underwent resection had gross clear margins,with 15 patients(38.5%) having either a gross or microscopic positive margin.All patients died.The 1-,2-,and 3-year overall survival(OS) rates for the entire cohort of 45 patients were 53.3%,35.6%and 13.5%,respectively.The independent prognostic factors associated with high OS rate were tumor size and treatment type.Conclusions:RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention.Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.

Phase Ⅰ clinical study of personalized peptide vaccination combined with radiotherapy for advanced hepatocellular carcinoma

AIM To assess the efficacy and safety of a new treatment modality, cellular immune therapy based on personalized peptide vaccination(PPV-DC-CTL) combined with radiotherapy, for treating advanced hepatocellular carcinoma(HCC). METHODS A total of nine patients with advanced HCC were enrolled. Multidisciplinary consultation confirmed that all the patients definitely had no opportunity of surgery, because four patients had multiple liver metastases(the number of liver lesions > 3), one patient had liver metastases and portal vein tumor thrombosis, one patient had lung and bone metastases, two patients had liver and lung metastases and one patient had liver metastasis and peritoneal metastasis. Patients with metastasis were treated with precise radiotherapy combined with PPV-DC-CTL.RESULTS Following radiotherapy and one to three cycles of PPV-DC-CTL treatment, AFP levels were significantly decreased in six patients and imaging assessment of the lesions showed a partial response(PR) in three patients and stable disease in the other three patients. The response rate was 33% and disease control rate was 66%. This regimen was found to be safe and well tolerated. None of the patients developed liver or kidney side effects. Only one patient developed grade Ⅱ bone marrow suppression and the remaining patients had no significant hematological side effects.CONCLUSION Radiotherapy combined with PPV-DC-CTL provides a new therapeutic strategy for patients with advanced HCC, which is well tolerated, safe, feasible and effective.