Toward the Non-surgical Management of Locally Advanced Rectal Cancer

Neoadjuvant short-course radiotherapy and long-course chemoradiation (CRT) reduce local recurrence rates when compared to surgery alone and remain widely accepted as standard of care for patients with locally advanced rectal cancer. However, surgery is not without complications and a non-surgical approach in carefully selected patients warrants evaluation. A pathological complete response to CRT is associated with a significant improvement in survival and it has been suggested that a longer time interval between the completion of CRT and surgery increases tumor downstaging. Intensification of neoadjuvant treatment regimens to increase tumor downstaging has been evaluated in a number of clinical trials and more recently the introduction of neoadjuvant chemotherapy prior to CRT has demonstrated high rates of radiological tumor regression. Careful selection of patients using high-resolution MRI may allow a non-surgical approach in a subgroup of patients achieving a complete response to neoadjuvant therapies after an adequate time period. Clearly this needs prospective evaluation within a clinical trial setting, incorporating modern imaging techniques, and tissue biomarkers to allow accurate prediction and assessment of response.     

Nonoperative approaches to rectal cancer: a critical evaluation

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institution's experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer.     

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.     

Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683)

BACKGROUND:

Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies.

METHODS:

Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5‐fluorouracil‐based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data.

RESULTS:

In total, 99 patients were included in the study. Twenty‐three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false‐negative and 10 false‐positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%.

CONCLUSIONS:

Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501–3511. © 2011 American Cancer Society.     

MicroRNA in rectal cancer

In rectal cancer, one of the most common cancers worldwide, the proper staging of the disease determines the subsequent therapy. For those with locally advanced rectal cancer, a neoadjuvant chemoradiotherapy (CRT) is recommended before any surgery. However, response to CRT ranges from complete response (responders) to complete resistance (non-responders). To date we are not able to separate in advance the first group from the second, due to the absence of a valid biomarker. Therefore all patients receive the same therapy regardless of whether they reap benefits. On the other hand almost all patients receive a surgical resection after the CRT, although a watch-and-wait procedure or an endoscopic resection might be sufficient for those who responded well to the CRT. Being highly conserved regulators of gene expression, microRNAs (miRNAs) seem to be promising candidates for biomarkers. Many studies have been analyzing the miRNAs expressed in rectal cancer tissue to determine a specific miRNA profile for the ailment. Unfortunately, there is only a small overlap of identified miRNAs between different studies, posing the question as to whether different methods or differences in tissue storage may contribute to that fact or if the results simply are not reproducible, due to unknown factors with undetected influences on miRNA expression. Other studies sought to find miRNAs which correlate to clinical parameters (tumor grade, nodal stage, metastasis, survival) and therapy response. Although several miRNAs seem to have an impact on the response to CRT or might predict nodal stage, there is still only little overlap between different studies. We here aimed to summarize the current literature on rectal cancer and miRNA expression with respect to the different relevant clinical parameters.     

直肠癌新辅助治疗后临床完全缓解的评估

新辅助治疗已成为局部晚期直肠癌的标准治疗模式。新辅助治疗后对肿瘤反应进行评估及再分期对于制定患者后续的治疗策略和预测肿瘤的预后至关重要。有一部分患者在新辅助治疗后能达到临床完全缓解甚至病理完全缓解,而在病理未明确之前如何评估临床缓解一直是目前国内外专家关注的焦点。本文就直肠癌新辅助治疗后的最佳评估时间和评估方法的进展进行综述。     

Interval Between Surgery and Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Does Delayed Surgery Have an Impact on Outcome?

BACKGROUND: The optimal interval between neoadjuvant chemoradiation therapy (CRT) and surgery in the treatment of patients with distal rectal cancer is controversial. The purpose of this study is to evaluate whether this interval has an impact on survival. METHODS AND MATERIALS: Patients who underwent surgery after CRT were retrospectively reviewed. Patients with a sustained complete clinical response (cCR) 1 year after CRT were excluded from this study. Clinical and pathologic characteristics and overall and disease-free survival were compared between patients undergoing surgery 12 weeks or less from CRT and patients undergoing surgery longer than 12 weeks from CRT completion and between patients with a surgery delay caused by a suspected cCR and those with a delay for other reasons. RESULTS: Two hundred fifty patients underwent surgery, and 48.4% had CRT-to-surgery intervals of 12 weeks or less. There were no statistical differences in overall survival (86% vs. 81.6%) or disease-free survival rates (56.5% and 58.9%) between patients according to interval (< or =12 vs. >12 weeks). Patients with intervals of 12 weeks or less had significantly higher rates of Stage III disease (34% vs. 20%; p = 0.009). The delay in surgery was caused by a suspected cCR in 23 patients (interval, 48 +/- 10.3 weeks). Five-year overall and disease-free survival rates for this subset were 84.9% and 51.6%, not significantly different compared with the remaining group (84%; p = 0.96 and 57.8%; p = 0.76, respectively). CONCLUSIONS: Delay in surgery for the evaluation of tumor response after neoadjuvant CRT is safe and does not negatively affect survival. These results support the hypothesis that shorter intervals may interrupt ongoing tumor necrosis.     

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.     

The predictive value of clinical evaluation of response to neoadjuvant chemoradiation therapy for rectal cancer

INTRODUCTION: Multimodality therapy has become the standard treatment for patients with locally advanced (T3 and T4) rectal carcinoma. Accurate preoperative staging of the patients with rectal cancer has increased in importance because the selection of patients with transmural rectal cancer (T3 or T4) or node-positive disease leads to a previous nonsurgical neoadjuvant treatment. The purpose of this study was to evaluate the predictive value of the clinical response to neoadjuvant therapy on the basis of pathological results obtained on rectal cancer patients treated by chemoradiotherapy and surgery. METHODS: From 1994 to 2003, 58 patients with a primary diagnosis of rectal cancer were studied at our department and enrolled in a neoadjuvant protocol of chemoradiotherapy followed by surgery. All patients were treated by 30 days of chemoradiotherapy. At the end of the chemoradiotherapy, each patient underwent clinical examination, including digital rectal examination, proctoscopy and abdominal-pelvic computerized tomography to define the clinical response to the chemoradiotherapy. Surgical resection was performed in all patients three weeks after the end of chemoradiotherapy, and histological analysis was performed on all resected specimens. RESULTS: The clinical complete response rate corresponded to the pathological complete response rate, whereas the clinical evaluation overestimated partial response and stable disease. The pathologic examination revealed that 3.5% of clinical partial responses and 3.4% of clinical stable disease were really pathological progressive disease. Clinical partial response and clinical stable disease positive predictive values were 92.8% and 90.9%, respectively, whereas the clinical progressive disease negative predictive value was 20%. Then, 6.9% of patients believed to have responded to the therapy, or not to have responded or worsened, actually had worsened by the end of the chemoradiotherapy. CONCLUSIONS: Positive and negative predictive values, in particular for partial response and stable disease, of clinical evaluation of the response to chemoradiotherapy were not high enough to consider clinical evaluation accurate enough to make treatment decisions.     

Locally advanced rectal cancer: what is the evidence for induction chemoradiation?

The concept of spatial cooperation in neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer is attractive. Chemotherapy may, as a component of CRT, not only act as a radiosensitizing agent but also potentially eradicate distant micrometastases. Recent trials have demonstrated that the addition of concurrent 5-fluorouracil (5-FU)-based chemotherapy to radiation increases the pathological complete response rate, and reduces local recurrence, but as yet, a survival advantage has not been observed. AIMS: This review aims to examine the evidence for induction CRT in locally advanced rectal cancer. The endpoints of pathological complete response, a negative circumferential margin, sphincter-sparing surgery, local control, disease-free survival (DFS), and overall survival (OS) are examined, as are acute and late morbidity, surgical complications, and late functional results. METHODS: The information to produce this review was compiled by searching PubMed and MEDLINE for English language articles published until April 2007. The search term included "induction, neoadjuvant, chemotherapy, radiotherapy, chemoradiation, combined modality" in association with rectal cancer. CONCLUSIONS: CRT in the European randomized trials of rectal cancer improves tumor downstaging, pathological complete response, and local control over radiotherapy alone, but does not translate into a benefit in terms of longer DFS or OS, or a higher chance of sphincter preservation. Metastatic disease remains a significant problem, which provides a strong rationale for the integration of a second cytotoxic drug, or biologically targeted agents.     

Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial

AimsWe assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer.Materials and methodsThis was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin–5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%.ResultsBetween October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases.ConclusionFOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.     

直肠癌新辅助治疗后临床完全缓解患者不同处理措施预后效果的Meta分析

目的以Meta分析评价针对新辅助治疗后达临床完全缓解的直肠癌患者行根治性手术、局部切除以及非手术临床观察的效果,为临床决策提供临床依据。方法以"rectal cancer"、"rectal adenocarcinoma"、"rectal neoplasms"、"neoadjuvant therapy"、"preoperative therapy"、"radiochemotherapy"、"radiotherapy"、"clinical complete response"、"complete pathological response"为主题词,在PubMed上收集有关直肠癌临床完全缓解患者进行根治性手术、局部切除和非手术治疗临床观察的公开发表的英文文献。纳入局部切除与根治性手术预后情况对比文献5篇,非手术临床观察与局部切除对比文献5篇。经两名研究者独立提取相关数据资料后进行Meta分析,用定性方法比较各预后指标在非手术组与根治性手术组、局切组与根治性手术组间的差异。利用漏斗图法评价发表偏倚。结果定性分析结果显示,与根治性手术组相比,非手术治疗临床观察组局部复发RR为5.33,95%CI为1.64~17.36,总复发RR为2.37,95%CI为1.15~4.85,差异有统计学意义;但远处转移率(RR=0.87,95%CI:0.16~41.11)及3~5年总生存率(RR=0.89,95%CI:0.66~1.21)则无统计学差异。与根治性手术组相比,局部切除组局部复发率(RR=1.25,95%CI:0.64~2.44)、远处转移率(RR=0.55,95%CI:0.27~1.10)及总复发率(RR=0.77,95%CI:0.49~1.22)均无统计学差异,且5年总生存率局部切除组界值性高于根治性手术组(P0.05)。结论直肠癌新辅助治疗后达临床完全缓解患者行非手术观察的局部复发率、总复发率高于根治性手术,但远处转移、长期生存与根治性手术相比无显著差异。局部切除术的局部复发率、远处转移率与根治性手术相比无显著差异,行局部切除者术长期生存甚至优于根治性手术。     

新辅助化疗联合手术治疗直肠腹膜返折部癌84例

[目的]探讨新辅助化疗联合手术治疗直肠腹膜返折部癌的临床疗效。[方法]回顾性研究2007年1月至2009年5月146例直肠腹膜返折部癌患者的资料,146例患者分为综合治疗组（新辅助化疗＋手术治疗）（n=84）和单纯手术组（n=62）,比较两组临床疗效。[结果]两组手术类型、肿瘤缓解度、术中出血量、手术前后CEA值、并发症情况及术后首次排气、排便、下床活动时间均无统计学差异（P〉0.05）。两组环周切缘均阴性。综合治疗组的手术时间较单纯手术组短（P〈0.05）;综合治疗组盆腹膜充血率较单纯手术组高（P〈0.05）。综合治疗组的复发率低于单纯手术组（P〈0.05）。[结论]新辅助化疗联合手术治疗直肠腹膜返折部癌具有良好的围手术期安全性,可以改善临床远期疗效,降低术后局部复发率。     

Delaying surgery after neoadjuvant chemoradiotherapy in rectal cancer has no influence in surgical approach or short-term clinical outcomes

Aims

In rectal cancer, increasing the interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery could improve the pathological complete response (pCR) rates, allow full-dose neoadjuvant chemotherapy, and select patients with a clinical complete response (cCR) for inclusion in a “watch & wait” program (W&W). However, controversy arises from waiting more than 8–12 weeks after CRT, as it might increase fibrosis around the total mesorectal excision (TME) plane potentially leading to technical difficulties and higher surgical morbidity. This study evaluates the type of surgical approach and short term post-operative outcomes in patients with rectal cancer that were operated before and after 12 weeks post CRT.

Neoadjuvant FOLFIRINOX followed by Chemoradiotherapy for Middle and Lower Rectal Cancer

Objective: Neoadjuvant concomitant chemoradiotherapy followed by surgical resection is the standard of care in the treatment of rectal cancer. We are investigating the value of adding combination chemotherapy oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX) before neoadjuvant chemoradiotherapy. Methods: Forty-one patients with middle and lower rectal cancer were included. FOLFORINOX were given every 2 weeks over 2 months (4 cycles) followed by concomitant chemoradiotherapy (CRT). Surgery was done 6-8 weeks after CRT and then adjuvant 4 months of FOLFOX or XELOX were given. The primary end point was sphincter preservation rate. Results: All patients received the four cycles of neoadjuvant chemotherapy FOLFORINOX, 38 patients completed CRT and only 29 patients underwent surgery. 32 patients were available for assessment (29 patients who underwent surgery and three patients who refuse surgery because of no evidence of disease by endoscopy, imaging and biopsy). Sphincter preservation was achieved in twenty-one patients (51.2%). Pathological complete response rate was 24.1%. After a median follow up of 24 months. Median PFS was 20 months and 2-years PFS was 62.3%. The median overall survival of all patients was not reached, while 2-years OS was 76.5%. Conclusion: Neoadjuvant FOLFIRINOX followed by CRT for middle and lower rectal cancer is feasible, tolerable with satisfactory sphincter preservation rate.     

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy in patients with locally advanced rectal cancer. In 2004, a study revealed that chemoradiotherapy (CRT) resulted in better local control when performed preoperatively rather than postoperatively, thus neoadjuvant treatment was established as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant difference between concomitant CRT over 5 wk vs short-course radiotherapy (RT). Therefore, both were established as standard neoadjuvant treatments. Later, the Stockholm III study demonstrated that short-course RT had a higher complete pathological response than long-course RT. It also showed that a delay between RT and surgery presented fewer complications. This opened a window of time to provide an early and effective systemic treatment to prevent distant metastases. Studies show that short-course RT plus oxaliplatin-based chemotherapy could achieve this. When comparing this total neoadjuvant treatment (TNT) vs concomitant CRT, the former showed greater complete pathological response and lower acute toxicity. Studies presented during 2020 have also shown the benefits of TNT in terms of complete pathological response, as well as disease and metastasis-free survival. Our review suggests that probably TNT should be the new standard treatment for these patients. However, we will have to wait for the full text publications of these studies to confirm this statement.     

Pathologic Implications of Magnetic Resonance Imaging-detected Extramural Venous Invasion of Rectal Cancer

BackgroundExtramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. Recent advances in magnetic resonance imaging (MRI) allow for the detection of EMVI before surgery. This study aimed to analyze the correlations between MRI-detected EMVI (MR-EMVI) and pathologic parameters in patients with rectal cancer.Materials and MethodsThis study retrospectively analyzed 721 patients who underwent radical resection for locally advanced rectal cancer between 2018 and 2019 at the Asan Medical center. All patients underwent an MRI before surgery. The lesions of patients who received neoadjuvant chemoradiation therapy (CRT) were evaluated by MRI before and after the neoadjuvant CRT.ResultsOf the 721 patients, 118 (16.4%) showed a positive MR-EMVI, which significantly correlated with advanced pathologic T-category and N-category, extranodal extension, poor differentiation, lymphatic invasion, venous invasion, and perineural invasion. In addition, MR-EMVI was an independent factor for predicting the pathologic nodal status (OR 3.476, 95% CI, 2.186-5.527, P < .001). Patients with a positive MR-EMVI had a sensitivity of 28.0% and specificity of 91.9% for predicting regional lymph node metastasis, whereas the MR-N category had a sensitivity of 88.7% and specificity of 30.6%. Patients whose MR-EMVI changed from positive to negative after neoadjuvant CRT had no significant differences in pathologic parameters except for lymphatic invasion with patients who were negative before and after neoadjuvant CRT.ConclusionMR-EMVI correlated with aggressive pathologic features, which indicated a poor prognosis. MR-EMVI may be a complementary imaging biomarker for predicting nodal status and evaluating tumor response to neoadjuvant CRT.     

Chemoradiation therapy for esophageal cancer

The current status and future prospects of chemoradiation therapy (CRT) for esophageal cancer are reviewed herein. In Western countries, CRT is performed for every stage of esophageal cancer and it has been reported that in definitive CRT series the complete response rate is 30 to 50%, the mean survival rate more than twelve months, and the in 2-year survival rate about 30%, while in neoadjuvant CRT series the pathological response rate is 20 to 50%, the mean survival period more than twenty months, and the 3-year survival 30 to 40%. On the other hand, as esophageal cancer is treated mainly by surgery in Japan, CRT is applied in patients with tumors invading adjacent organs, and a high pathological complete response rate is reported in some neoadjuvant studies. Although both definitive and neoadjuvant CRT increases the response rate and improves local tumor control, CRT is associated with substantial mortality and morbidity, especially in neoadjuvant series. More effective and less toxic CRT regimens, using new chemotherapeutic agents such as nedaplatin and paclitaxel and new irradiation protocol such as accelerated hyperfractionation, are needed to improve the prognosis of patients with advanced esophageal cancer.     

Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.     

Controversial issues in the therapy of oesophageal carcinoma

There are still a lot of controversies regarding treatment strategies in oesophageal carcinoma due to lack of studies with adequate patient numbers and the inclusion of heterogeneous study populations. Some important news came from the CROSS trial regarding the value of neoadjuvant chemoradiation (CRT). Patients with resectable tumours were randomised to receive surgery alone or weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy. The overall survival in this well-powered study was significantly improved with neoadjuvant CRT resulting in a hazard ratio of 0.657. The control arm with surgery alone showed an exceptional good prognosis with a very low postoperative mortality rate of 4 % only. Also the neoadjuvant therapy showed very good tolerability, the postoperative mortality rate was not increased after neoadjuvant CRT. Only two randomised trials investigated the value of neoadjuvant CRT vs. chemotherapy (CT) in adenocarcinomas of the oesophago-gastric junction (EGJ). Both showed a non-significant trend in favour of neoadjuvant CRT, but both trials included only a limited number of patients. The value of an induction chemotherapy before CRT is still unproven, even if there are several arguments for it and it is daily practice in a lot of centres. Another remaining controversy exists about those patients having achieved a complete response to CRT. Does surgery play a role for the curative therapy of these patients or not? Also this issue is discussed in this review.