Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

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.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast

BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND Survival benefit of neoadjuvant chemotherapy(NAC)for advanced gastric cancer(AGC)is a debatable issue.Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs.For those who achieve pathological complete response(pCR),NAC significantly prolonged prolapsed-free survival and overall survival.For those with poor response,NAC yielded no survival benefit,only toxicity and increased risk for tumor progression during chemotherapy,which may hinder surgical resection.Thus,predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIM To establish a nomogram for predicting pCR to NAC for AGC patients.METHODS Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study.Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR.Based on these predictors,a nomogram model was developed and internally validated using the bootstrap method.RESULTS pCR was confirmed in 27 patients(27/208,13.0%).Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level,lymphocyte ratio,lower monocyte count and tumor differentiation grade were associated with higher pCR.Concordance statistic of the established nomogram was 0.767.CONCLUSION A nomogram predicting pCR to NAC was established.Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters,it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Unfavorable Pathological Complete Response Rate of Neoadjuvant Chemotherapy Epirubicin plus Taxanes for Locally Advanced Triple-negative Breast Cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer （TNBC）. Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m^2 plus paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response （pCR）, which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival （RFS） and overall survival （OS） were secondary endpoints. Thirty-nine （90.7%） patients were at clinical stages II B-IIIC. Thirty-seven （86%） completed 4-6 cycles of preop- erative chemotherapy, and objective response rate （ORR） was 81.4% （35/43）. Forty-two patients un- derwent radical surgery subsequently. The pCR rate was 14.3% （6/42）. The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting （88.4%, 38/43） and neutropenia （88.4%）. After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally ad- vanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor(GIST) . Computed tomography(CT) and magnetic resonance imaging(MRI) 107 mo after the operation,revealed a cystic mass(14 cm in diameter) and a solid mass(9 cm in diameter) in the right and left lobes of the liver,respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate(IM) treatment,400 mg/day orally. Following the IM treatment for a period of 35 mo,the patient underwent partial hepatectomy(S4 + S5) . The effect of IM on the metastatic lesions was interpreted as pathologic complete response(CR) . Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma:a single center experience

Objective:To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy(RT)or concurrent chemoradiotherapy(CCRT).Methods:This study recruited 64 patients.The patients had resectable cancer of the lower and the middle rectum(T3/T4 and/or N+)without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision(TME)between January 2006 and December 2011.The patients were classified into non-response(NR),partial response(PR),and pathologic complete response(p CR)based on the Dworak tumor regression grading system.Results:The median age of patients was 57 years(ranging from 22 to 85).A total of 24 patients were treated with neoadjuvant CCRT,whereas 40 patients were treated with RT alone.Abdominoperineal resection(APR)was performed on 29 patients(45%).Anterior resection with TME was performed on 34 patients(53%).One patient had local resection.Histologically,12(19%),24(73%),and 28(44%)patients exhibited p CR,PR,and NR,respectively.Univariate analysis revealed that the predictors of tumor regression were as follows:the absence of lymph node involvement from initial imaging(c N0)(P=0.021);normal initial carcinoembryonic antigen(CEA)level(P=0.01);hemoglobin level≥12 g/dl(P=0.009);CCRT(P=0.021);and tumor downstaging in imaging(P=0.001).Multivariate analysis showed that the main predictors of p CR were CT combined with neoadjuvant RT,c N0stage,and tumor regression on imaging.Conclusions:Identifying the predictors of p CR following neoadjuvant therapy aids the selection of responsive patients for nonaggressive surgical treatment and possible surveillance.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

Multidisciplinary approaches in the management of advanced hepatocellular carcinoma:Exploring future directions

Recently,we read the article“Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of the literature”published in the World Journal of Gastrointestinal Oncology.The prognosis of advanced hepatocellular carcinoma(HCC)is poor,and multidisciplinary comprehensive treatment is currently the main research direction.This case report demonstrated the efficacy of the combination therapy of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,epclusa,lenvatinib and sintilimab for a patient with advanced HCC,and the report can serve as a reference for clinical practice.We would also like to share some of our views.

CEA levels predict tumor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Objective The aim of this study was to evaluate the impact of serum carcinoembryonic antigen(CEA)in the prediction of pathological complete response(pCR)in locally advanced rectal cancer(LARC)patients treated with neoadjuvant chemoradiotherapy(nCRT).Methods A total of 925 LARC patients who underwent nCRT followed by TME between March 2006 and February 2018 were enrolled at Fudan University Shanghai Cancer Center.Using logistic regression models,we investigated the associations between serum CEA levels and pathological complete remission(pCR).Further stratified analyses were performed according to different CEA thresholds.Results We found that pre-nCRT CEA and post-nCRT CEA were negatively correlated with pCR(P<0.001).Stratified analyses revealed that when the CEA cutoff value was set to 5 ng/mL,10.6%of patients with post-nCRT CEA levels>5 ng/mL achieved pCR.Meanwhile,when the CEA cutoff value was set to 10 ng/mL,only 6.8%of the patients with post-nCRT CEA levels>10 ng/mL achieved pCR.Conclusion In summary,pre and post-nCRT CEA levels≤5 ng/mL were favorable predictors of pCR in LACR patients,and the“watch and wait”strategy is not recommended for patients with post-nCRT CEA levels>10 ng/mL.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

The management of rectal cancer has evolved significantly in the last few decades.Significant improvements in local disease control were achieved in the 1990s,with the introduction of total mesorectal excision and neoadjuvant radiotherapy.Level 1 evidence has shown that,with neoadjuvant chemoradiation therapy(CRT)the rates of local recurrence can be lower than 6%and,as a result,neoadjuvant CRT currently represents the accepted standard of care.This approach has led to reliable tumor down-staging,with 15–27%patients with a pathological complete response(pCR)—defined as no residual cancer found on histological examination of the specimen.Patients who achieve pCR after CRT have better long-term outcomes,less risk of developing local or distal recurrence and improved survival.For all these reasons,sphincter-preserving procedures or organ-preserving options have been suggested,such as local excision of residual tumor or the omission of surgery altogether.Although local recurrence rate has been stable at 5–6%with this multidisciplinary management method,distal recurrence rates for locally-advanced rectal cancers remain in excess of 25%and represent the main cause of death in these patients.For this reason,more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting(in order to offer early treatment of disseminated micrometastases,thus improving control of systemic disease)and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm.

Successful multidisciplinary therapy for a patient with liver metastasis from ascending colon adenocarcinoma:A case report and review of literature

BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approximately 25%of patients with CRLM have indications for liver resection at the initial diagnosis.Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases.Due to the huge lesion size and compression of the right portal vein,the liver metastases were initially diagnosed as unresectable lesions.The patient was treated with preoperative transcatheter arterial chemoembolization(TACE)consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®.After four courses,radical right-sided colectomy and ileum transverse colon anastomosis were performed.Postoperatively,the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins.Thereafter,S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy.Pathological examination of the resected specimen revealed a pathologically complete response(pCR).Intrahepatic recurrence was detected more than two months after the operation,and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®.Subsequently,the patient was treated with aγ-knife to enhance local control.Notably,a pCR was reached,and the patient's overall survival time was>9 years.CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.

Conversion immunotherapy for deficient mismatch repair locally unresectable colon cancer:A case report

BACKGROUND Owing to the special features of biologics,deficient mismatch repair(dMMR)in patients with colon cancer has achieved little treatment efficacy from chemoradiotherapy.Immunotherapy has shown promising results for the treatment of colon cancer.The high response rate observed suggests a great option for patients presenting with unresectable tumors,as it allows for better oncological resection.Here,we aimed to highlight the significant effects of immunotherapy on dMMR in colon cancer.CASE SUMMARY A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy(three cycles of pembrolizumab)and achieved a pathological complete response after surgery.CONCLUSION Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.

Nomogram for predicting pathological complete response and tumor downstaging in patients with locally advanced rectal cancer on the basis of a randomized clinical trial

Background:Preoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer(LARC).The model for predicting pCR in LARC patients was based on standard treatment only.This study aimed to establish a nomogramwith pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response(pCR)and tumor downstaging or good response(ypT0-2N0M0)after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial.Methods:Between January 2011 and February 2015,309 patients with rectal cancer were enrolled from a prospective randomized study(NCT01211210).All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging.The model was subjected to bootstrap internal validation.The predictive performance of the model was assessed with concordance index(C-index)and calibration plots.Results:Of the 309 patients,53(17.2%)achieved pCR and 132(42.7%)patients were classified as tumor downstaging with ypT0-2N0M0.Based on the logistic-regression analysis and clinical consideration,tumor length(P=0.005),tumor circumferential extent(P=0.036),distance from the anal verge(P=0.019),and neoadjuvant treatment regimen(P<0.001)showed independent association with pCR following neoadjuvant treatment.The tumor length(P=0.015),tumor circumferential extent(P=0.001),distance from the anal verge(P=0.032),clinical T category(P=0.012),and neoadjuvant treatment regimen(P=0.001)were significantly associated with good tumor downstaging(ypT0-2N0M0).Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802(95%confidential interval[CI],0.736-0.867)and 0.730(95%CI,0.672-0.784).Internal validation revealed good performance of the calibration plots.Conclusions:The nomogramprovided individual prediction responses to different preoperative treatment for patients with rectal cancer.This model might help physicians in selecting an optimized treatment,but warrants further external validation.

Advances for achieving a pathological complete response for rectal cancer after neoadjuvant therapy

Neoadjuvant therapy has become the standard of care for locally advanced mid-low rectal cancer. Pathological complete response (pCR) can be achieved in 12%e38% of patients. Patients with pCR have the most favorable long-term outcomes. Intensifying neoadjuvant therapy and extending the interval between termination of neoadjuvant treatment and surgery may in-crease the pCR rate. Growing evidence has raised the issue of whether local excision or observation rather than radical surgery is an alternative for patients who achieve a clinical complete response after neoadjuvant therapy. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for pCR of rectal cancer in the modern era.

Oxaliplatin-containing adjuvant chemotherapy improves the survival of locally advanced rectal cancer patients with pathological complete response after pre-operative chemoradiotherapy

Background:The necessity for adjuvant chemotherapy(ACT)in locally advanced rectal cancer(LARC)patients who achieve pathological complete response(pCR)after pre-operative chemoradiotherapy(CRT)is still not identified.We aimed to investigate the therapeutic value of ACT in these patients.Methods:Clinical data were retrospectively collected from 105 consecutive LARC patients who achieved pCR after pre-operative CRT and underwent radical tumor resection between December 2008 and April 2014 in a comprehensive cancer center.Perioperative chemotherapy(CT)was administered by combining oxaliplatin with capecitabine(XELOX regimen).Disease-free survival(DFS)and overall survival(OS)rates of patients with or without ACT were compared.Results:Eighty-three(79.0%)patients received ACT and 22(21.0%)did not.With a median follow-up of 49 months,the ACT group had a significantly higher 3-year DFS rate(92.8 vs 86.4%,p=0.029)and 3-year OS rate(95.1 vs 86.1%,p=0.026)than the non-ACT group.In multivariable analyses,the presence of ACT was an independent prognostic factor for DFS(hazard ratio[HR]:0.271;95%confidence interval(CI):0.080–0.916;p=0.036)but not for OS.This benefit was more obvious in patients younger than 60 years via subgroup analysis(adjusted HR:0.106;95%CI:0.019–0.606;p=0.012).Conclusions:Oxaliplatin-containing ACT may confer survival benefits to patients with pCR,particularly younger patients.However,the routine use of ACT in patients with pCR needs further validation.

Advances of pathological complete response after neoadjuvant therapy for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Only 15% to 20% of patients present with a primarily resectable tumor at the time of diagnosis. There has been an increasing interest in the use of neoadjuvant chemotherapy alone or combination with radiotherapy in patients with resectable, borderline resectable, and locally advanced pancreatic cancer. Although the benefit of neoadjuvant therapy on resectable patients remains controversial, around one third of borderline resectable and locally advanced patients could be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as those with primary resectable tumors. A pathological complete response (Pcr) in PDAC is an indicator for significantly better survival although it's rather rare. In this review, we present recent progress of Pcr and the controversies in pancreatic cancer after neoadjuvant therapy.

Neoadjuvant treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical resection.Neoadjuvant chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease.Treatment with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies.These immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term benefits.Importantly,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications.However,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival outcomes.Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer

Due to a wide range of clinical response in patients un-dergoing neo-adjuvant chemoradiation for rectal cancer it is essential to understand molecular factors that lead to the broad response observed in patients receiving the same form of treatment.Despite extensive research in this field,the exact mechanisms still remain elusive.Data raging from DNA-repair to specific molecules lead-ing to cell survival as well as resistance to apoptosis have been investigated.Individually,or in combination,there is no single pathway that has become clinically applicable to date.In the following review,we describe the current status of various pathways that might lead to resistance to the therapeutic applications of ionizing radiation in rectal cancer.