Neoadjuvant treatment for advanced esophageal cancer: response assessment before surgery and how to predict response to chemoradiation before starting treatment

Patients with advanced esophageal cancer（T3-4, N） have a poor prognosis. Chemoradiation or chemotherapy before esophagectomy with adequate lymphadenectomy is the standard treatment for patients with resectable advanced esophageal carcinoma. However, only patients with major histopathologic response（regression to less than 10% of the primary tumor） after preoperative treatment will have a prognostic benefit of preoperative chemoradiation. Using current therapy regimens about 40% to 50% of the patients show major histopathological response. The remaining cohort does not benefit from this neoadjuvant approach but might benefit from earlier surgical resection. Therefore, it is an aim to develop tools for response prediction before starting the treatment and for early response assessment identifying responders. The current review discusses the different imaging techniques and the most recent studies about molecular markers for early response prediction. The results show that [^18F]-fluorodeoxyglucose-positron emission tomography（FDGPET） has a good sensitivity but the specificity is not robust enough for routine clinical use. Newer positron emission tomography detector technology, the combination of FDG-PET with computed tomography, additional evaluation criteria and standardization of evaluation may improve the predictive value. There exist a great number of retrospective studies using molecular markers for prediction of response. Until now the clinical use is missing. But the results of first prospective studies are promising. A future perspective may be the combination of imaging technics and special molecular markers for individualized therapy. Another aspect is the response assessment after finishing neoadjuvant treatment protocol. The different clinical methods are discussed. The results show that until now no non-invasive method is valid enough to assess complete histopathological response.

Neoadjuvant therapy for resectable pancreatic cancer

The use of neoadjuvant therapies has played a major role for borderline resectable and locally advanced pancreatic cancers(PCs). For this group of patients, preoperative chemotherapy or chemoradiation has increased the likelihood of surgery with negative resection margins and overall survival. On the other hand, for patients with resectable PC, the main rationale for neoadjuvant therapy is that the overall survival with current strategies is unsatisfactory. There is a consensus that we need new treatments to improve the overall survival and quality of life of patients with PC. However, without strong scientific evidence supporting the theoretical advantages of neoadjuvant therapies, these potential benefits might turn out not to be worth the risk of tumors progression while waiting for surgery. The focus of this paper is to provide the readers an overview of the most recent evidence on this subject.

Radiation therapy prior to a pancreaticoduodenectomy for adenocarcinoma is associated with longer operative times and higher blood loss

BACKGROUND Pancreatic adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States.In patients with“borderline resectable”disease,current National Comprehensive Cancer Center guidelines recommend the use of neoadjuvant chemoradiation prior to a pancreaticoduodenectomy.Although neoadjuvant radiotherapy may improve negative margin resection rate,it is theorized that its administration increases operative times and complexity.AIM To investigate the association between neoadjuvant radiotherapy and 30-d morbidity and mortality outcomes among patients receiving a pancreaticoduodenectomy for pancreatic adenocarcinoma.METHODS Patients listed in the 2015-2019 National Surgery Quality Improvement Program data set,who received a pancreaticoduodenectomy for pancreatic adenocarcinoma,were divided into two groups based off neoadjuvant radiotherapy status.Multivariable regression was used to determine if there is a significant correlation between neoadjuvant radiotherapy,perioperative blood transfusion status,total operative time,and other perioperative outcomes.RESULTS Of the 11458 patients included in the study,1470(12.8%)underwent neoadjuvant radiotherapy.Patients who received neoadjuvant radiotherapy were significantly more likely to require a perioperative blood transfusion[adjusted odds ratio(aOR)=1.58,95%confidence interval(CI):1.37-1.82;P<0.001]and have longer surgeries(insulin receptor-related receptor=1.14,95%CI:1.11-1.16;P<0.001),while simultaneously having lower rates of organ space infections(aOR=0.80,95%CI:0.66-0.97;P=0.02)and pancreatic fistula formation(aOR=0.50,95%CI:0.40-0.63;P<0.001)compared to those who underwent surgery alone.CONCLUSION Neoadjuvant radiotherapy,while not associated with increased mortality,will impact the complexity of surgical resection in patients with pancreatic adenocarcinoma.

The role of liver transplantation for hilar cholangiocarcinoma

BACKGROUND: Hilar cholangiocarcinoma is a devastating disease. Surgery is the only potentially curative modality. However, the results of surgical resection for hilar cholangiocarcinomas are disappointing. The introduction of liver transplantation for this condition has brought new hope for the management of this disease. The aim of this review is to discuss the role of liver transplantation in this disease. DATA SOURCES: A MEDLINE search was conducted for the articles on liver transplantation for hilar cholangiocarcinoma. Their results have been compiled and compared with the existing literature on resection for this disease. RESULTS: The earlier series on liver transplantation for hilar cholangiocarcinoma were not encouraging because of poor patient selection. The Mayo Clinic protocol of neoadjuvant chemoradiation followed by liver transplantation has shown remarkable success (survival at 1-, 3-, and 5-year post-transplantation being 92%, 82%, and 82%, respectively). With better patient selection and integration of neoadjuvant chemoradiation, the long-term survival is superior to that of the patients who undergo resection, as shown by the published literature on resection. The limitations of organ availability can be overcome by the living donor liver transplantation programme. This review article discusses the rationale, pros and cons of liver transplantation vis-à-vis resection for hilar cholangiocarcinoma.CONCLUSIONS: Liver transplantation, especially living donor liver transplantation, is a new and exciting alternative to resection for hilar cholangiocarcinoma. Integration of neoadjuvant chemoradiation has the potential to further improve the curative potential of liver transplantation. The strategy of combining neoadjuvant chemoradiation and liver transplantation brings new hope for the treatment of this difficult disease.

Prognostic value of changes in serum carcinoembryonic antigen levels for preoperative chemoradiotherapy response in locally advanced rectal cancer

BACKGROUND Preoperative chemoradiotherapy(CRT)is a standard treatment modality for locally advanced rectal cancer.However,CRT alone cannot improve overall survival.Approximately 20%of patients with CRT-resistant tumors show disease progression.Therefore,predictive factors for treatment response are needed to identify patients who will benefit from CRT.We theorized that the prognosis may vary if patients are classified according to pre-to post-CRT changes in carcinoembryonic antigen(CEA)levels.AIM To identify patients with locally advanced rectal cancer for preoperative chemoradiotherapy based on carcinoembryonic antigen levels.METHODS We retrospectively included locally advanced rectal cancer patients who underwent preoperative CRT and curative resection between 2011 and 2017.Patients were assigned to groups A,B,and C based on pre-and post-CRT serum CEA levels:Both>5;pre>5 and post≤5;and both≤5 ng/mL,respectively.We compared the response to CRT based on changes in serum CEA levels.Receiver operating characteristic curve analysis was performed to determine optimal cutoff for neutrophil–lymphocyte ratio and platelet–lymphocyte ratio.Multivariate logistic regression analysis was used to evaluate the prognostic factors for pathologic complete response(pCR)/good response.RESULTS The cohort comprised 145 patients;of them,27,43,and 65 belonged to groups A,B,and C,respectively,according to changes in serum CEA levels before and after CRT.Pre-(P<0.001)and post-CRT(P<0.001)CEA levels and the ratio of downstaging(P=0.013)were higher in Groups B and C than in Group A.The ratio of pathologic tumor regression grade 0/1 significantly differed among the groups(P=0.003).Group C had the highest number of patients showing pCR(P<0.001).Most patients with pCR showed pre-and post-CRT CEA levels<5 ng/mL(P<0.001,P=0.008).Pre-and post-CRT CEA levels were important risk factors for pCR(OR=18.71;95%CI:4.62–129.51,P<0.001)and good response(OR=5.07;95%CI:1.92–14.83,P=0.002),respectively.Pre-CRT neutrophil–lymphocyte ratio and post-CRT T≥3 stage were also prognostic factors for pCR or good response.CONCLUSION Pre-and post-CRT CEA levels,as well as change in CEA levels,were prognostic markers for treatment response to CRT and may facilitate treatment individualization for rectal cancer.

Predictive significance of cancer related-inflammatory markers in locally advanced rectal cancer

BACKGROUND Locally advanced rectal cancer is treated using neoadjuvant chemoradiation(nCRT),followed by total mesorectal excision(TME).Tumor regression and pathological post-treatment stage are prognostic for oncological outcomes.There is a significant correlation between markers representing cancer-related inflammation,including high neutrophil-to-lymphocyte ratio(NLR),monocyteto-lymphocyte ratio(MLR),and platelet-to-lymphocyte(MLR)and unfavorable oncological outcomes.However,the predictive role of these markers on the effect of chemoradiation is unknown.AIM To evaluate the predictive roles of NLR,MLR,and PLR in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiation.METHODS Patients(n=111)with locally advanced rectal cancer who underwent nCRT followed by TME at the Minimally Invasive Surgery Unit,Siriraj Hospital between 2012 and 2018 were retrospectively analyzed.The associations between post-treatment pathological stages,neoadjuvant rectal(NAR)score and the pretreatment ratios of markers of inflammation(NLR,MLR,and PLR)were analyzed.RESULTS Clinical stages determined using computed tomography,magnetic resonance imaging,or both were T4(n=16),T3(n=94),and T2(n=1).The NAR scores were categorized as high(score>16)in 23.4%,intermediate(score 8-16)in 41.4%,and low(score<8)in 35.2%.The mean values of the NLR,PLR,and MLR correlated with pathological tumor staging(ypT)and the NAR score.The values of NLR,PLR and MLR were higher in patients with advanced pathological stage and high NAR scores,but not statistically significant.CONCLUSION In patients with locally advanced rectal cancer,pretreatment NLR,MLR and PLR are higher in those with advanced pathological stage but the differences are not significantly different.