Analysis of Clinical Effect of Concurrent Chemo/radiotherapy in the Treatment of Advanced Cervical Cancer

The study aimed to analyze the efficacy and adverse effects of concurrent chemo/radiotherapy in the treatment of advanced cervical cancer,and the efficacy and safety of concurrent chemo/radiotherapy were evaluated to standardize the treatment.First of all,retrospective analysis was carried out,and 30 cases of advanced cervical cancer treated in hospitals from 2013 to 2018 were included in the study.30 cases of concurrent chemo/radiotherapy were included in the synchronous group,and 30 cases of radical radiotherapy alone were included in the radiotherapy group.The results showed that the CR rate and remission rate in the synchronous group were 43.3%and 93.3%,which were higher than those in the radiotherapy group(26.7%and 80.0%).The 3-year survival rate of the synchronous group was 80.0%,which was higher than that of the radiotherapy group,with a statistically significant difference(P<0.05).There was no significant difference in 3-year all-cause mortality,5-year survival and 5-year allcause mortality between the two groups.The tumor-free survival time in the synchronous group was(24.4±8.2)months,which was higher than that in the radiotherapy group(17.0±8.5)months,and the difference was statistically significant(P<0.05).Therefore,compared with radiotherapy alone,concurrent chemo/radiotherapy in the treatment of advanced cervical cancer can improve the 3-year survival rate and prolong the tumor-free survival time.However,it did not increase 5-year survival rate,and bone marrow suppression and gastrointestinal reactions were increased.

Chemotherapy and radiotherapy:Could they contribute to the development of new tumors and metastases?

Objective: Both chemotherapy and radiotherapy have demonstrated high effectiveness as the best mechanisms in the fight against cancer;however, various studies seem to confirm that they could also favor the development of other unwanted effects of great importance for the patient. The main objective of this study is to find out the possible existence of this type of links. Method: This is a systematic literature review that seeks to find out which and how long cases of late interactions related to chemotherapy and radiotherapy treatments have been known. The bibliographic review was carried out based on references published in the last five years. Results: Various studies confirm the possible relationship between chemotherapy and radiotherapy treatments with the development of new undesirable side effects, especially as a consequence of the hepatotoxicity generated in the case of chemotherapy and radiation in radiotherapy. However, in this last type of treatment, the problems raised are really few. Conclusions: The existence of a risk of suffering new unwanted side effects after different types of treatment seems to have been demonstrated, especially in the case of chemotherapy. In the case of radiotherapy, adverse effects are practically non-existent, although they are no less important.

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.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma(CEC)patients who underwent definitive chemoradiotherapy(CRT).The clinical data of 175 biopsyconfirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed.The prognostic factors predicting overall survival(OS),progression-free survival(PFS),and local recurrence-free survival(LRFS)were assessed in uni-and multivariable analyses.The median age of the entire cohort was 56 years(range:26–87 years).All patients received definitive radiotherapy with a median total dose of 60 Gy,and 52%of the patients received cisplatin-based concurrent chemotherapy.The 2-year OS,PFS,and LRFS rates were 58.8%,46.9%,and 52.4%,respectively,with a median follow-up duration of 41.6 months.Patients’performance status,clinical nodal stage,tumor size,and treatment response were significant prognostic factors for OS,PFS,and LRFS in univariate analysis.Non-complete treatment response was an independent predictor for poor OS(HR=4.41,95%CI,2.78–7.00,p<0.001)and PFS(HR=4.28,95%CI,2.79–6.58,p<0.001),whereas poor performance score was a predictor for worse LRFS(HR=1.83,95%CI,1.12–2.98,p=0.02)in multivariable analysis.Fifty-two patients(29.7%)experienced grade II or higher toxicity.In this multicenter study,we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC.Higher radiation doses were found to have no effect on treatment outcomes,but a better response to treatment and a better patient performance status did.

Advanced gastric cancer achieving major pathologic regression after chemoimmunotherapy combined with hypofractionated radiotherapy: A case report

BACKGROUND Currently,chemotherapy combined with immunotherapy is the established firstline standard treatment for advanced gastric cancer(GC).In addition,the combination of radiotherapy and immunotherapy is considered a promising treatment strategy.CASE SUMMARY In this report,we present a case of achieving nearly complete remission of highly advanced GC with comprehensive therapies.A 67-year-old male patient was referred to the hospital because he presented with dyspepsia and melena for several days.Based on fluorodeoxyglucose positron emission tomography/computed tomography(FDG PET/CT),endoscopic examination and abdominal CT,he was diagnosed with GC with a massive lesion and two distant metastatic lesions.The patient received mFOLFOX6 regimen chemotherapy,nivolumab and a short course of hypofractionated radiotherapy(4 Gy×6 fractions)targeting the primary lesion.After the completion of these therapies,the tumor and the metastatic lesions showed a partial response.After having this case discussed by a multidisciplinary team,the patient underwent surgery,including total gastrectomy and D2 lymph node dissection.Postoperative pathology showed that major pathological regression of the primary lesion was achieved.Chemoimmuno therapy started four weeks after surgery,and examination was performed every three months.Since surgery,the patient has been stable and healthy with no evidence of recurrence.CONCLUSION The combination of radiotherapy and immunotherapy for GC is worthy of further exploration.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma:comparison of long-term outcome between radiotherapy and chemotherapy

AIM:To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma(NRSTS),and to compare the treatment outcome between postoperative radiotherapy(RT) and chemotherapy in a retrospective analysis nearly 20y.METHODS:A retrospective cohort study of 56 patients with orbital NRSTS were reviewed,34 of whom received postoperative RT,and 22 received postoperative chemotherapy.The clinicopathological features,local recurrence,metastases,and survival data were recorded.Survival analysis was performed using the Kaplan-Meier method.RESULTS:During follow-up(111.8mo,ranged 8-233mo) for 56 patients,19 patients of them developed local recurrence,and 7 patients developed distant metastases.Fifteen patients died during follow-up period.Overall survival rates considering the whole study group was 78.57% at 5y,and 72.16% at 10y after the initial diagnosis.Compared with chemotherapy,RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy,0.263,95% confidence interval(CI),0.095-0.728,P=0.0015];with lower risk of distant metastasis(hazard ratio for RT vs chemotherapy,0.073,95%CI,0.015-0.364,P=0.0014);and with lower risk of death from disease(hazard ratio for RT vs chemotherapy,0.066,95%CI,0.022-0.200,P<0.0001).The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group.CONCLUSION:In patients with orbital NRSTS,postoperative RT provides better control of local recurrence,distant metastasis,and death from disease than chemotherapy.RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Chemotherapy-free radiotherapy combined with immune checkpoint inhibitors:a new regimen for locally advanced non-small cell lung cancer?

Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Analysis of Status and Influencing Factors of Psychology Resilience Level in Cancer Patients Undergoing Radiotherapy and Chemotherapy

Objective:To analyse the status and discuss influencing factors of the psychology resilience level of cancer patients undergoing radiotherapy and chemotherapy,and to provide evidence for clinical rehabilitation intervention.Methods:A total of 320 patients with cancer undergoing radiotherapy and chemotherapy who were hospitalized in the Affiliated Hospital of North China University of Science and Technology and Tangshan Worker’s Hospital in China from September 2022 to November 2022 were selected as the research subjects.The surveys were conducted using the general information questionnaire,Connor-Davidson Scale(CD-RICS),Perceived Social Support Scale(PSSS)and Pittsburgh Sleep Quality Index Scale(PSQI).Results:The psychology resilience score of cancer patients undergoing radiotherapy and chemotherapy was 64.23±15.20,lower than the average level of resilience of adults in China(70.50±13.48)and American adults’normal value(80.4±12.8).Perceived social support was 58.13±14.04 and positively correlated with the level of psychology resilience(r=0.210,P<0.05).Sleep quality was 10.57±4.85,which showed most people have sleep quality disorder and was negatively correlated with the level of psychology resilience(r=-0.200,P<0.05).Multiple linear regression analysis showed that age,education level and disease stage were the main influencing factors in the level of psychological resilience in cancer patients undergoing radiotherapy and chemotherapy(P<0.05).Conclusions:The level of psychological resilience of cancer patients undergoing radiotherapy and chemotherapy is at a low level,and there are many influencing factors.Targeted medical care should be carried out according to the factors affecting the level of resilience to promote the mental health of patients.

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.

Enhancing Precision in Radiotherapy Delivery: Validating Monte Carlo Simulation Models for 6 MV Elekta Synergy Agility LINAC Photon Beam Using Two Models of the GAMOS Code

The most crucial requirement in radiation therapy treatment planning is a fast and accurate treatment planning system that minimizes damage to healthy tissues surrounding cancer cells. The use of Monte Carlo toolkits has become indispensable for research aimed at precisely determining the dose in radiotherapy. Among the numerous algorithms developed in recent years, the GAMOS code, which utilizes the Geant4 toolkit for Monte Carlo simula-tions, incorporates various electromagnetic physics models and multiple scattering models for simulating particle interactions with matter. This makes it a valuable tool for dose calculations in medical applications and throughout the patient’s volume. The aim of this present work aims to vali-date the GAMOS code for the simulation of a 6 MV photon-beam output from the Elekta Synergy Agility linear accelerator. The simulation involves mod-eling the major components of the accelerator head and the interactions of the radiation beam with a homogeneous water phantom and particle information was collected following the modeling of the phase space. This space was po-sitioned under the X and Y jaws, utilizing three electromagnetic physics mod-els of the GAMOS code: Standard, Penelope, and Low-Energy, along with three multiple scattering models: Goudsmit-Saunderson, Urban, and Wentzel-VI. The obtained phase space file was used as a particle source to simulate dose distributions (depth-dose and dose profile) for field sizes of 5 × 5 cm2 and 10 × 10 cm2 at depths of 10 cm and 20 cm in a water phantom, with a source-surface distance (SSD) of 90 cm from the target. We compared the three electromagnetic physics models and the three multiple scattering mod-els of the GAMOS code to experimental results. Validation of our results was performed using the gamma index, with an acceptability criterion of 3% for the dose difference (DD) and 3 mm for the distance-to-agreement (DTA). We achieved agreements of 94% and 96%, respectively, between simulation and experimentation for the three electromagnetic physics models and three mul-tiple scattering models, for field sizes of 5 × 5 cm2 and 10 × 10 cm2 for depth-dose curves. For dose profile curves, a good agreement of 100% was found between simulation and experimentation for the three electromagnetic physics models, as well as for the three multiple scattering models for a field size of 5 × 5 cm2 at 10 cm and 20 cm depths. For a field size of 10 × 10 cm2, the Penelope model dominated with 98% for 10 cm, along with the three multiple scattering models. The Penelope model and the Standard model, along with the three multiple scattering models, dominated with 100% for 20 cm. Our study, which compared these different GAMOS code models, can be crucial for enhancing the accuracy and quality of radiotherapy, contributing to more effective patient treatment. Our research compares various electro-magnetic physics models and multiple scattering models with experimental measurements, enabling us to choose the models that produce the most reli-able results, thereby directly impacting the quality of simulations. This en-hances confidence in using these models for treatment planning. Our re-search consistently contributes to the progress of Monte Carlo simulation techniques in radiation therapy, enriching the scientific literature.

Radiotherapy for hyoid bone metastasis from lung adenocarcinoma:A case report

BACKGROUND Metastasis to the hyoid bone is an exceptionally rare occurrence,with documented cases limited to breast,liver,colon,skin,lung,and prostate cancers.This report highlights an unusual case involving the metastasis of lung adenocarcinoma to the hyoid bone,accompanied by a distinctive headache.Previous documentation involved surgical resection of the hyoid mass.We present a case displaying the benefits of palliative radiotherapy.CASE SUMMARY A 72-year-old non-smoking,non-alcoholic woman,initially under investigation for a year-long elevation in absolute lymphocyte count,presented with a monthlong history of intermittent throat pain.Despite negative findings in gastroenterological and otolaryngologic examinations,a contrast-enhanced chest computed tomography scan revealed a mediastinal mass and questionable soft tissue thickening in her left anterolateral neck.Subsequent imaging and biopsies confirmed the presence of lung adenocarcinoma metastasis to the hyoid bone.The patient was treated with platinum-based chemo-immunotherapy along with pembrolizumab.Ultimately,the lung cancer was unresponsive.Our patient opted for palliative radiation therapy instead of surgical resection to address her throat pain.As a result,her throat pain was alleviated,and it also incidentally resolved her chronic headaches.This is the second documented case of lung adenocarcinoma metastasizing to the hyoid bone.CONCLUSION Palliative radiotherapy may add to the quality of life in symptomatic patients with cancer metastatic to the hyoid bone.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Changes in acute and late toxicity and patient-reported health-related quality of life following radiotherapy in women with breast cancer:A 1-year longitudinal study

Objective:The objective of this study was to investigate the frequency of acute and late toxicities,as well as changes in the quality of life(QOL)for breast cancer patients following radiotherapy(RT).Materials and Methods:A total of 108 breast cancer women were recruited for this prospective study.Data were collected at various intervals;prior to,and 1,3,6 months,and 1 year after radiation therapy.The primary outcomes were toxicity radiation therapy oncology group/European Organization for Research and Treatment of Cancer(EORTC)criteria.Our secondary outcome was QOL,measured using EORTC QLQ-C30 and Edmonton Symptom Assessment Scale.We employed Friedman’s two-way analysis to evaluate the changes in QOL over the course of 1 year.Results:The early toxicities that are most commonly experienced include pharyngeal,skin,and mucous membrane toxicity.Late toxicities frequently involve skin and submucosal toxicity.To measure patient functionality,all functional subscale scores except for the patient’s emotional state increased over time compared to pre-RT.Symptoms of the patients,which were included in the QOL symptom scale,decreased during the follow-up period,except for fatigue;however,changes in pain,insomnia,and loss of appetite did not significantly change.We identified the analogous symptom profiles in Edmonton.Although patients’overall health scores declined in the 1st and 3rd months after radiotherapy(RT),they rebounded at 6 and 12 months.Conclusion:For breast cancer patients,RT did not adversely affect functional capacity or exacerbate symptoms,but persistent fatigue did increase during the observation period.Health-care professionals ought to devise strategies to assist patients with skin toxicity and fatigue.

Subgroups of peripheral immune effector cells in cervical cancer patients are more sensitive to radiation therapy than chemotherapy

Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.

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.

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.

PhaseⅠ/Ⅱtrial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma

Background: After deinitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma(NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present signiicant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can beneit from these treatments. Re-irradiation with X-ray—based intensity-modulated radiotherapy(IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radioresistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy(CIRT). In addition, CIRT is a high linear energy transfer(LET) radiation and provides an increased relative biological efectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 Gy E(gray equivalent), at 2.5 Gy E per daily fraction, was well tolerated in patients who were previously treated for NPC with a deinitive dose of IMXT. The short-term response rates at 3–6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can beneit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the beneits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results.Methods and design: The maximal tolerated dose(MTD) of re-treatment using raster-scanning CIRT plus concurrent cisplatin will be determined in the phase I, dose-escalating stage of this study. CIRT dose escalation from 52.5 to 65 Gy E(2.5 Gy E × 21–26 fractions) will be delivered, with the primary endpoints being acute and subacute toxicities. Eicacy in terms of overall survival(OS) and local progression-free survival of patients after concurrent chemotherapy plus CIRT at the determined MTD will then be studied in the phase II stage of the trial. We hypothesize that CIRT plus chemotherapy can improve the 2-year OS rate from the historical 50% to at least 70%.Conclusions: Re-treatment of locally recurrent NPC using photon radiation techniques, including IMXT, provides moderate eicacy but causes potentially severe toxicities. Improved outcomes in terms of eicacy and toxicity proile are expected with CIRT plus chemotherapy. However, the MTD of CIRT used concurrently with cisplatin-based chemotherapy for locally recurrent NPC remains to be determined. In addition, whether the addition of chemotherapy to CIRT is needed remains unknown. These questions will be evaluated in the dose-escalating phase I and randomized phase II trials.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

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.