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.

Improving the utility of locally differentially private protocols for longitudinal and multidimensional frequency estimates

This paper investigates the problem of collecting multidimensional data throughout time(i.e.,longitudinal studies)for the fundamental task of frequency estimation under Local Differential Privacy(LDP)guarantees.Contrary to frequency estimation of a single attribute,the multidimensional aspect demands particular attention to the privacy budget.Besides,when collecting user statistics longitudinally,privacy progressively degrades.Indeed,the“multiple”settings in combination(i.e.,many attributes and several collections throughout time)impose several challenges,for which this paper proposes the first solution for frequency estimates under LDP.To tackle these issues,we extend the analysis of three state-of-the-art LDP protocols(Generalized Randomized Response–GRR,Optimized Unary Encoding–OUE,and Symmetric Unary Encoding–SUE)for both longitudinal and multidimensional data collections.While the known literature uses OUE and SUE for two rounds of sanitization(a.k.a.memoization),i.e.,L-OUE and L-SUE,respectively,we analytically and experimentally show that starting with OUE and then with SUE provides higher data utility(i.e.,L-OSUE).Also,for attributes with small domain sizes,we propose Longitudinal GRR(L-GRR),which provides higher utility than the other protocols based on unary encoding.Last,we also propose a new solution named Adaptive LDP for LOngitudinal and Multidimensional FREquency Estimates(ALLOMFREE),which randomly samples a single attribute to be sent with the whole privacy budget and adaptively selects the optimal protocol,i.e.,either L-GRR or L-OSUE.As shown in the results,ALLOMFREE consistently and considerably outperforms the state-of-the-art L-SUE and L-OUE protocols in the quality of the frequency estimates.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics

BACKGROUND Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy(nCRT)for rectal cancer.However,the underlying mechanisms remain elusive.AIM To detect the differential expression profiles of plasma exosomal microRNAs(miRNAs)in poor and good responders and explore the potential mechanisms of chemoresistance.METHODS In this study,the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses(poor/good responders)and treatment courses(pre/post-nCRT)using RNA sequencing.RESULTS Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT.Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways,such as the MAPK signaling pathway,EGFR tyrosine kinase inhibitor resistance,Toll-like receptor signaling pathway,VEGF signaling pathway,and mTOR signaling pathway.Further analysis indicated that MAPK3,RAX2,and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer,and the profiles of MAPK3,TSPYL5,and ZNF-417 were correlated with tumor stage.In addition,the expression profiles of MAPK3,RNF165,and ZNF417 were negatively correlated with inhibitory concentration 50 values.Accordingly,an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed.CONCLUSION This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs.However,further research is required within the framework of our established miRNA-mRNA network.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Programmed cell death 1 inhibitor sintilimab plus concurrent chemoradiotherapy for locally advanced pancreatic adenocarcinoma

BACKGROUND Pancreatic adenocarcinoma,a malignancy that arises in the cells of the pancreas,is a devastating disease with unclear etiology and often poor prognosis.Locally advanced pancreatic cancer,a stage where the tumor has grown significantly but has not yet spread to distant organs,presents unique challenges in treatment.This article aims to discuss the current strategies,challenges,and future directions in the management of locally advanced pancreatic adenocarcinoma(LAPC).AIM To investigate the feasibility and efficacy of programmed cell death 1(PD-1)inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.METHODS Eligible patients had LAPC,an Eastern cooperative oncology group performance status of 0 or 1,adequate organ and marrow functions,and no prior anticancer therapy.In the observation group,participants received intravenous sintilimab 200 mg once every 3 wk,and received concurrent chemoradiotherapy(concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-140 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression,death,or unacceptable toxicity).In the control group,participants only received concurrent chemoradiotherapy.From April 2020 to November 2021,64 participants were finally enrolled with 34 in the observation group and 30 in the control group.RESULTS Thirty-four patients completed the scheduled course of chemoradiotherapy,while 32(94.1%)received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group.Thirty patients completed the scheduled course of chemoradiotherapy in the control group.Based on the Response Evaluation Criteria in Solid Tumors guidelines,the analysis of the observation group revealed that a partial response was observed in 11 patients(32.4%),stable disease was evident in 19 patients(55.9%),and 4 patients(11.8%)experienced progressive disease;a partial response was observed in 6(20.0%)patients,stable disease in 18(60%),and progressive disease in 6(20%)in the control group.The major toxic effects were leukopenia and nausea.The incidence of severe adverse events(AEs)(grade 3 or 4)was 26.5%(9/34)in the observation group and 23.3%(7/30)in the control group.There were no treatment-related deaths.The observation group demonstrated a significantly longer median overall survival(22.1 mo compared to 15.8 mo)(P<0.05)and progression-free survival(12.2 mo vs 10.1 mo)(P<0.05)in comparison to the control group.The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group(P>0.05).CONCLUSION Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients,and warrants further investigation.

Minimally invasive pelvic exenteration for primary or recurrent locally advanced rectal cancer:A glimpse into the future

Surgeons have grappled with the treatment of recurrent and T4b locally advanced rectal cancer(LARC)for many years.Their main objectives are to increase the overall survival and quality of life of the patients and to mitigate postoperative complications.Currently,pelvic exenteration(PE)with or without neoadjuvant treatment is a curative treatment when negative resection margins are achieved.The traditional open approach has been favored by many surgeons.However,the technological advancements in minimally invasive surgery have radically changed the surgical options.Recent studies have demonstrated promising results in postoperative complications and oncological outcomes after robotic or laparoscopic PE.A recent retrospective study entitled“Feasibility and safety of minimally invasive multivisceral resection for T4b rectal cancer:A 9-year review”was published in the World Journal of Gastrointestinal Surgery.As we read this article with great interest,we decided to delve into the latest data regarding the benefits and risks of minimally invasive PE for LARC.Currently,the small number of suitable patients,limited surgeon experience,and steep learning curve are hindering the establishment of minimally invasive PE.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Navigating the pathways:TAR-DNA-binding-protein-43 aggregation,axonal transport,and local synthesis in amyotrophic lateral sclerosis pathology

Neurons are highly polarized cells with axons reaching over a meter long in adult humans.To survive and maintain their proper function,neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events,which need to be carried out at the right place,time,and intensity.Such mechanisms include axonal transport,local synthesis,and liquid-liquid phase separations.Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS).

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study

BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.

Locally varying geostatistical machine learning for spatial prediction

Machine learning methods dealing with the spatial auto-correlation of the response variable have garnered significant attention in the context of spatial prediction.Nonetheless,under these methods,the relationship between the response variable and explanatory variables is assumed to be homogeneous throughout the entire study area.This assumption,known as spatial stationarity,is very questionable in real-world situations due to the influence of contextual factors.Therefore,allowing the relationship between the target variable and predictor variables to vary spatially within the study region is more reasonable.However,existing machine learning techniques accounting for the spatially varying relationship between the dependent variable and the predictor variables do not capture the spatial auto-correlation of the dependent variable itself.Moreover,under these techniques,local machine learning models are effectively built using only fewer observations,which can lead to well-known issues such as over-fitting and the curse of dimensionality.This paper introduces a novel geostatistical machine learning approach where both the spatial auto-correlation of the response variable and the spatial non-stationarity of the regression relationship between the response and predictor variables are explicitly considered.The basic idea consists of relying on the local stationarity assumption to build a collection of local machine learning models while leveraging on the local spatial auto-correlation of the response variable to locally augment the training dataset.The proposed method’s effectiveness is showcased via experiments conducted on synthetic spatial data with known characteristics as well as real-world spatial data.In the synthetic(resp.real)case study,the proposed method’s predictive accuracy,as indicated by the Root Mean Square Error(RMSE)on the test set,is 17%(resp.7%)better than that of popular machine learning methods dealing with the response variable’s spatial auto-correlation.Additionally,this method is not only valuable for spatial prediction but also offers a deeper understanding of how the relationship between the target and predictor variables varies across space,and it can even be used to investigate the local significance of predictor variables.

Construction controlling and strength increasing characteristics of locally developed epoxy asphalt mixture

The construction controlling elements,including construction performance at low ambient temperatures,reserved time ranges,and the strength increasing rule,for locally developed epoxy asphalt mixture（LDEAM） are studied through laboratory tests.Air void and Marshall stability are chosen as the performance measures for evaluating the construction quality.The wheel rolling test is used to simulate the actual construction situations,while the Marshall test and the Brookfield viscosity test are adopted to study the strength increasing rule.The experimental results reveal that the LDEAM can be constructed under a low ambient temperature condition of 10℃,and its longest reserved time is 70 min at a reserved temperature of 120℃.Test also shows that the strength of the LDEAM increases with time and temperature before cured.Finally,the theoretical reason for the strength increasing rule is analyzed on the basis of the organic chemistry theory.

Locally linear embedding-based seismic attribute extraction and applications

How to extract optimal composite attributes from a variety of conventional seismic attributes to detect reservoir features is a reservoir predication key,which is usually solved by reducing dimensionality.Principle component analysis（PCA） is the most widely-used linear dimensionality reduction method at present.However,the relationships between seismic attributes and reservoir features are non-linear,so seismic attribute dimensionality reduction based on linear transforms can＇t solve non-linear problems well,reducing reservoir prediction precision.As a new non-linear learning method,manifold learning supplies a new method for seismic attribute analysis.It can discover the intrinsic features and rules hidden in the data by computing low-dimensional,neighborhood-preserving embeddings of high-dimensional inputs.In this paper,we try to extract seismic attributes using locally linear embedding（LLE）,realizing inter-horizon attributes dimensionality reduction of 3D seismic data first and discuss the optimization of its key parameters.Combining model analysis and case studies,we compare the dimensionality reduction and clustering effects of LLE and PCA,both of which indicate that LLE can retain the intrinsic structure of the inputs.The composite attributes and clustering results based on LLE better characterize the distribution of sedimentary facies,reservoir,and even reservoir fluids.

The Submanifolds with Parallel Mean Curvature Vector in a Locally Symmetric and Conformally Flat Riemannian Manifold

In the present paper we obtain the following result: Theorem Let M^R be a compact submanifold with parallel mean curvature vector in a locally symmetric and conformally flat Riemannian manifold N^(n+p)(p>1). If then M^n lies in a totally geodesic submanifold N^(n+1).

Accurate evaluation of lowest band gaps in ternary locally resonant phononic crystals

Based on a better understanding of the lattice vibration modes, two simple spring-mass models are constructed in order to evaluate the frequencies on both the lower and upper edges of the lowest locally resonant band gaps of the ternary locally resonant phononic crystals. The parameters of the models are given in a reasonable way based on the physical insight into the band gap mechanism. Both the lumped-mass methods and our models are used in the study of the influences of structural and the material parameters on frequencies on both edges of the lowest gaps in the ternary locally resonant phononic crystals. The analytical evaluations with our models and the theoretical predictions with the lumped-mass method are in good agreement with each other. The newly proposed heuristic models are helpful for a better understanding of the locally resonant band gap mechanism, as well as more accurate evaluation of the band edge frequencies.

Management of borderline and locally advanced pancreatic cancer:Where do we stand?

Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field.

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.

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.

Outcomes of locally advanced prostate cancer:a single institution study of 209 patients in Japan

Aim： To investigate the outcomes for Asian populations with locally advanced/clinical stage Ⅲ prostate cancer （PCa） treated with currently prevailing modalities. Methods： We reviewed the record of 209 patients with clinical stage Ⅲ PCa, who were treated at Niigata Cancer Center Hospital between 1992 and 2003. Treatment options included hormone therapy-combined radical prostatectomy （RP＋HT）, hormone therapy-combined external beam irradiation （EBRT＋HT） and primary hormone therapy （PHT）. Results： The 5- and 10-year overall survival rates were 80.3% and 46.1% in all cohorts, respectively. The survival rates were 87.3% and 66.5% in the RP＋HT group, 94.9% and 70.0% in the EBRT＋HT group and 66.1% and 17.2% in the PHT group, respectively. A significant survival advantage was found in the EBRT＋HT group compared with that in the PHT group （P 〈 0.0001）. Also, the RP＋HT group had better survival than the PHT group （P = 0.0107）. The 5- and 10-year disease-specific survival rates for all cases were 92.5% and 80.0%, respectively. They were 93.8% and 71.4% in the RP＋HT group, 96.6% and 93.6% in the EBRT＋HT group and 88.6% and 62.3% in the PHT group, respectively. A survival advantage was found in the EBRT＋HT group compared with the PHT group （P = 0.029）. No significant difference was found in disease-specific survival between the EBRT＋HT and RP＋HT groups or between the RP＋HT and PHT groups. Condusion： Although our findings indicate that radiotherapy plus HT has a survival advantage in this stage of PCa, we recommend therapies that take into account the patients＇ social and medical conditions for Asian men with clinical stage Ⅲ PCa.