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.

Association of tumor differentiation and prognosis in patients with rectal cancer undergoing neoadjuvant chemoradiation therapy

Background and objective:Neoadjuvant chemoradiation therapy(NCRT)followed by radical resection has been a common practice for patients with locally advanced rectal cancer.This study aimed to analyse the association of tumor differentiation and prognosis in rectal-cancer patients undergoing NCRT.Methods:Patients with locally advanced,non-mucinous rectal cancer who underwent NCRT followed by radical resection between 2007 and 2017 were identified from an electronic health record system at the Sixth Affiliated Hospital of Sun Yatsen University(Guangzhou,China).Multivariable logistic regression and multivariate Cox regression were performed to analyse the association of response to NCRT and survival with clinicopathological characteristics of all these patients.Results:We identified 325 patients(241 males and 84 females;mean age,54.4611.2 years)who underwent NCRT followed by radical resection,including 26(8.0%)with poorly-differentiated rectal cancer,182(56.0%)with moderately-differentiated cancer and 117(36.0%)with well differentiated cancer.Propensity score matching analysis and multivariable logistic regression analysis results showed that tumor differentiation was significantly associated with response to NCRT.In the poor differentiation and non-poor differentiation groups,the 3-year overall survival(OS)rates were 74.6 and 93.5%,respectively,whereas the 3-year local recurrence rates were 18.6 and 3.7%,respectively.Multivariable Cox regression analyses revealed that poor differentiation was an independent risk factor for local recurrence and OS.Conclusions:Among the patients with locally advanced,non-mucinous rectal cancer,the patients with poorlydifferentiated cancer who underwent NCRT had a worse response to NCRT and poorer prognosis than those with moderately-and well-differentiated diseases.

Endoscopic ultrasound and magnetic resonance imaging for re-staging rectal cancer after radiotherapy

AIM： To compare the sensitivity and specificity of two imaging techniques, endoscopic ultrasound （EUS） and magnetic resonance imaging （MRI）, in patients with rectal cancer after neoadjuvant chemoradiation therapy. And we compared EUS and MRI data with histological findings from surgical specimens. METHODS： Thirty-nine consecutive patients （51.3% Male; mean age： 68.2 ＋ 8.9 years） with histologically confirmed distal rectal cancer were examined for staging. All patients underwent EUS and MRI imaging before and after neoadjuvant chemoradiation therapy. RESULTS： After neoadjuvant chemoradiation, EUS and MRI correctly classified 46% （18/39） and 44% （17/39） of patients, respectively, in line with their histological T stage （P 〉 0.05）. These proportions were higher for both techniques when nodal involvement was considered： 69% （27/39） and 62% （24/39）. When patients were sorted into T and N subgroups, the diagnostic accuracy of EUS was better than MRI for patients with T0-T2 （44% vs 33%, P 〉 0.05） and NO disease （87% vs 52%, P = 0.013）. However, MRI was more accurate than EUS in T and N staging for patients with more advanced disease after radiotherapy, though these differences did not reach statistical significance. CONCLUSION： EUS and MRI are accurate imaging techniques for staging rectal cancer, However, after neoadjuvant RT-CT, the role of both methods in the assessment of residual rectal tumors remains uncertain.

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.

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.

Computed tomography perfusion imaging as a potential imaging biomarker of colorectal cancer

Neovascularization was reported to arise early in the adenoma-carcinoma sequence in colorectal cancer(CRC),and the importance of angiogenesis in cancer progression has been established.Computed tomography(CT)perfusion(CTP)based on high temporal resolution CT images enables evaluation of hemodynamics of tissue in vivo by modeling tracer kinetics.CTP has been reported to characterize tumor angiogenesis,and to be a sensitive marker for predicting recurrence or survival in CRC.In this review,we will discuss the biomarker value of CTP in the management of CRC patients.

Interval to surgery after neoadjuvant treatment for colorectal cancer

The current standard treatment of low-lying locally advanced rectal cancer consists of chemoradiation followed by radical surgery.The interval between chemoradiation and surgery varied for many years until the1999 Lyon R90-01 trial which compared the effects of a short(2-wk)and long(6-wk)interval.Results showed a better clinical tumor response(71.7%vs 53.1%)and higher rate of positive and pathologic tumor regression(26%vs 10.3%)after the longer interval.Accordingly,a 6-wk interval between chemoradiation and surgery was set to balance the oncological results with the surgical complexity.However,several recent retrospective studies reported that prolonging the interval beyond 8or even 12 wk may lead to significantly higher rates of tumor downstaging and pathologic complete response.This in turn,according to some reports,may improve overall and disease-free survival,without increasing the surgical difficulty or complications.This work reviews the data on the effect of different intervals,derived mostly from retrospective analyses using a wide variation of treatment protocols.Prospective randomized trials are currently ongoing.

Anal squamous cell carcinoma: An evolution in disease and management

Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.

Adjuvant treatment in biliary tract cancer: To treat or not to treat?

Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic man- agement. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of ad- juvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Welldesigned multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase Ⅲ trials may provide relevant information.

Anal carcinoma-exploring the epidemiology,risk factors,pathophysiology,diagnosis,and treatment

Anal carcinoma is a relatively rare tumor that accounts for approximately 2%of gastrointestinal malignancies and less than 7%of anorectal cancers.Most anal tumors originate between the anorectal junction and the anal verge.Risk factors for the disease include human papillomavirus infection,human immunodeficiency virus,tobacco use,immunosuppression,female sex,and older age.The pathogenesis of anal carcinoma is believed to be linked to human papillomavirusrelated inflammation,leading to dysplasia and progression to cancer.Squamous cell carcinoma is the most common type of anal tumor,with an annual incidence of approximately 1 to 2 per 100000 persons.Treatment regarding anal cancer has emerged over time.However,chemoradiation therapy remains the mainstay approach for early localized disease.Patients with metastatic disease are treated with systemic therapy,and salvage surgery is reserved for disease recurrence following chemoradiation.This article aims to provide background information on the epidemiology,risk factors,pathology,diagnosis,and current trends in the management of anal cancer.Future directions are briefly discussed.