Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.

Paired-related homeobox 1 induces epithelial-mesenchymal transition in oesophageal squamous cancer

BACKGROUND It is unclear that paired-related homeobox 1(PRRX1)induces epithelialmesenchymal transition(EMT)in oesophageal cancer and the specific function of PRRX1 in oesophageal cancer metastasis.AIM To assess the signicance of PRRX1 expression and investigate the mechanism of EMT in oesophageal cancer metastasis.METHODS Detect the expression of PRRX1 by immunohistochemistry in oesophageal tumour tissues and adjacent normal oesophageal tissues;the PRRX1 short hairpin RNA(shRNA)or blank vector lentiviral gene delivery system was transfected into cells;cell proliferation assay,soft agar colony formation assays,cell invasion and migration assays and animal studies were used to observe cells biological characteristics In vitro and in vivo;XAV939 and LiCl were used to alter the activity of Wnt/β-catenin pathway.Immunofluorescence staining and western blot analysis were used to detect protein expression of EMT markers and Wnt/β-catenin pathway.RESULTS PRRX1 is expressed at high levels in oesophageal cancer specimens and is closely related to tumour metastasis in patients with oesophageal cancer.Regulation of PRRX1 expression might exert obvious effects on cell proliferation,especially the migration and invasion of oesophageal cancer cells.Moreover,silencing PRRX1 expression using a shRNA produced the opposite effects.In addition,when PRRX1 was overexpressed,inhibition of the Wnt/β-catenin pathway with XAV939 negated the effect of PRRX1 on EMT,whereas when PRRX1 was downregulated,activation of the Wnt/β-catenin pathway with LiCl impaired the effect on EMT.CONCLUSION PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis.Additionally,PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.

Characterisation and risk assessment of venous thromboembolism in gastrointestinal cancers

AIM To characterise venous thromboembolism(VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring. METHODS We performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal(GO) cancer and 1299 colorectal cancer(CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival.VTE risk scores were calculated using the Khorana index. Patients were classified as low risk(0 points), intermediate risk(1 to 2 points) or high risk(3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE. RESULTS The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli(PE) were more common in advanced than in localised CRC(50% vs 21% of events respectively) and lower limb deep vein thrombosis(DVT) were more common in localised than in advanced CRC(62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score(94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be factored into clinical risk assessment scores. CONCLUSION The Khorana score has low sensitivity for thrombotic events in CRC and cannot discriminate low risk patients in high risk cancer sites such as GO cancer.

Impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma

BACKGROUND In the contemporary era of cancer immunotherapy,an abundance of clinical and translational studies have reported radiotherapy(RT)and immunotherapies as a viable option for immunomodulation of many cancer subtypes,with many related clinical trials ongoing.In locally advanced disease,chemotherapy or chemoradiotherapy followed by surgical excision of the tumour remain the principal treatment strategy in oesophageal adenocarcinoma(OAC),however,the use of the host immune system to improve anti-tumour immunity is rapidly garnering increased support in the curative setting.AIM To immunophenotype OAC patients’immune checkpoint(IC)expression with and without radiation and evaluate the effects of checkpoint blockade on cell viability.METHODS In the contemporary era of cancer immunotherapy,an abundance of studies have demonstrated that combination RT and IC inhibitors(ICIs)are effective in the immunomodulation of many cancer subtypes,with many related clinical trials ongoing.Although surgical excision and elimination of tumour cells by chemotherapy or chemoradiotherapy remains the gold standard approach in OAC,the propagation of anti-tumour immune responses is rapidly garnering increased support in the curative setting.The aim of this body of work was to immunophenotype OAC patients’IC expression with and without radiation and to establish the impact of checkpoint blockade on cell viability.This study was a hybrid combination of in vitro and ex vivo models.Quantification of serum immune proteins was performed by enzyme-linked immunosorbent assay.Flow cytometry staining was performed to evaluate IC expression for in vitro OAC cell lines and ex vivo OAC biopsies.Cell viability in the presence of radiation with and without IC blockade was assessed by a cell counting kit-8 assay.RESULTS We identified that conventional dosing and hypofractionated approaches resulted in increased IC expression(PD-1,PD-L1,TIM3,TIGIT)in vitro and ex vivo in OAC.There were two distinct subcohorts with one demonstrating significant upregulation of ICs and the contrary in the other cohort.Increasing IC expression post RT was associated with a more aggressive tumour phenotype and adverse features of tumour biology.The use of anti-PD-1 and anti-PD-L1 immunotherapies in combination with radiation resulted in a significant and synergistic reduction in viability of both radiosensitive and radioresistant OAC cells in vitro.Interleukin-21(IL-21)and IL-31 significantly increased,with a concomitant reduction in IL-23 as a consequence of 4 Gray radiation.Similarly,radiation induced an anti-angiogenic tumour milieu with reduced expression of vascular endothelial growth factor-A,basic fibroblast growth factor,Flt-1 and placental growth factor.CONCLUSION The findings of the current study demonstrate synergistic potential for the use of ICIs and ionising radiation to potentiate established anti-tumour responses in the neoadjuvant setting and is of particular interest in those with advanced disease,adverse features of tumour biology and poor treatment responses to conventional therapies.

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers

BACKGROUND Image-guided radiotherapy(IGRT)has significantly improved the precision in which radiotherapy is delivered in cancer treatment.Typically,IGRT uses bony landmarks and key anatomical structures to locate the tumor.Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue.The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied.However,placement requires expertise and specialized endoscopic ultrasound equipment.This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT.AIM To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients.METHODS A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne,Australia was conducted.Up to four liquid fiducials were inserted per patient,each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil(Lipiodol;Aspen Pharmacare)and n-butyl 2-cyanoacrylate(Histoacryl®;B.Braun).A 23-gauge injector(Cook Medical)was used for the injection.All procedures were performed by or under the supervision of a gastroenterologist.Liquid fiducial-based IGRT(LF-IGRT)consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy.Patients received standard-IGRT(S-IGRT)if fiducial visibility was insufficient,consisting of bone match as a surrogate for tumor position.Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments.RESULTS 52 patients were referred for liquid fiducial placement within the study period.A total of 51 patients underwent liquid fiducial implantation.Of these a total of 31 patients received radiotherapy.Among these,the median age was 77.4 years with a range between 57.5 and 88.8,and 64.5%were male.Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT.There were no complications after endoscopic implantation of liquid fiducials in our cohort.The cohort overall survival(OS)post-radiotherapy was 19 mo(range 0 to 87 mo).Whilst the progression-free survival(PFS)post-radiotherapy was 13 mo(range 0 to 74 mo).For those treated with curative intent,the median OS was 22.0 mo(range 0 to 87 mo)with a PFS median of 14.0 mo(range 0 to 74 mo).Grade 3 complication rate post-radiotherapy was 29%.CONCLUSION LF-IGRT is feasible in 87.1%of patients undergoing liquid fiducial placement through standard gastroscopy injection technique.Our cohort has an overall survival of 19 mo and PFS of 13 mo.Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.

Primary small cell oesophageal carcinoma: A retrospective study of different treatment modalities

BACKGROUND Primary small cell of esophageal carcinoma is an aggressive tumor with no established treatment guidelines.A treatment strategy was adopted based on small cell carcinoma of the lung because of many similar clinicopathological features.Here,we report one of the largest case series in a western population.AIM To review the practice of treating small cell oesophageal cancer(SCOC)with different treatment modalities treated at our institution between 2001 and 2014.METHODS A total of 28 cases of SCOC have been identified.All cases were identified with a ten-digit code known as the CHI number.Data was collected using a combination of an electronic database,case notes and the chemotherapy electronic prescribing system(chemocare).We collected information on age,gender,performance status,staging of the disease(limited stage vs extensive stage).RESULTS The results showed 17 patients(61%)were diagnosed with limited stage small cell oesophageal cancer(LS-SCOC),while 11 patients(39%)were diagnosed with extensive stage small cell oesophageal cancer(ES-SCOC).The median age at diagnosis of SCOC was 72 years(range 52-86).The median survival for patients with ES-SCOC was 7 mo(95%CI:1-12)vs LS-SCOC[median 23 mo(95%CI:14-40)],P<0.0001.Subgroup analysis of those who received treatment showed the median survival for patients who received palliative chemotherapy was 7 mo(95%CI:1.5-12),concurrent chemoradiation 45 mo(95%CI:38-)and sequential chemoradiation 20 mo(95%CI:17-25),P<0.0001.CONCLUSION Our data strongly support the use of concurrent chemoradiation in the treatment of LS-SCOC in patients who are fit with no significant comorbidity.

Iatrogenic Oesophageal Perforations in Neoplastic Lesions: Management with Covered Self-Expanding Prostheses

Background:Perforation of the oesophagus is a serious condition. Most of them are iatrogenic and are associated with significant morbidity and mortality, especially with late diagnosis. Aim: To prospectively analyse the results of the endoscopic management of iatrogenic perforations in oesophageal neoplasia, through the immediate insertion of a covered self-expanding prosthesis (CSES). Materials and Methods: Between 01.01.2006 and 12.30.2016, a series of 19 consecutive patients attended the Teaching Unit of Endoscopic Surgery of the Regional de Concepción Hospital, Chile, with the diagnosis of oesophageal neoplasia confirmed by biopsy were prospectively studied. All were subjected to a prior evaluation by the oncology team and subsequently referred for endoscopic palliative management of dysphagia. The average age was 77 ± 9.3 years, 8 (42.1%) were female and 11 (57.9%) were male. In 17 patients (89.5%) the stenosis compromised the oesophagus, in 2 (10.5%) the gastro-oesophageal junction, 16 had a squamous carcinoma (84.2%) and 3 an adenocarcinoma (15.8%). Results: Perforation was diagnosed during the procedure in 18 patients (94.7%) and in 1 (5.3%) 22 hours later. Follow-up was done for a minimum of 90 days or until death. The prostheses were inserted successfully in all cases. The immediate evolution was satisfactory in 12 patients (63.2%). In the rest (36.8%), 18 complications appeared. The most frequent were retrosternal pain, subcutaneous emphysema and fever. The early evolution was satisfactory in 12/19 cases (63.2%). Complication was evidenced in 7 (36.8%), the most frequent was retrosternal pain (36.8%). Fever occurred in 3 (15.8%), pleural effusion in 3 (15.8%) and mediastinitis in 2 of these. The prosthesis was kept in situ as a definitive palliation method for neoplastic dysphagia. In 10 of the 18 cases that survived more than a month, there were late complications (55.6%), none of them associated with the perforation itself. The only death (5.3%) was due to an oesophagus-pleural fistula, associated with an early prosthetic migration. Recovery of the oral intake occurred, on average, at 3.7 days. The hospital stay averaged 9.6 days. Conclusion: The use of CSES for the treatment of iatrogenic oesophageal perforations in the context of neoplasia, is a safe and effective method, with low morbidity, adequate recovery of the oral intake and prompt discharge from hospital.

Preoperative risk modelling for oesophagectomy: A systematic review

BACKGROUND Oesophageal cancer is a frequently observed and lethal malignancy worldwide.Surgical resection remains a realistic option for curative intent in the early stages of the disease.However,the decision to undertake oesophagectomy is significant as it exposes the patient to a substantial risk of morbidity and mortality.Therefore,appropriate patient selection,counselling and resource allocation is important.Many tools have been developed to aid surgeons in appropriate decision-making.AIM To examine all multivariate risk models that use preoperative and intraoperative information and establish which have the most clinical utility.METHODS A systematic review of the MEDLINE,EMBASE and Cochrane databases was conducted from 2000-2020.The search terms applied were((Oesophagectomy)AND(Risk OR predict OR model OR score)AND(Outcomes OR complications OR morbidity OR mortality OR length of stay OR anastomotic leak)).The applied inclusion criteria were articles assessing multivariate based tools using exclusively preoperatively available data to predict perioperative patient outcomes following oesophagectomy.The exclusion criteria were publications that described models requiring intra-operative or post-operative data and articles appraising only univariate predictors such as American Society of Anesthesiologists score,cardiopulmonary fitness or pre-operative sarcopenia.Articles that exclusively assessed distant outcomes such as long-term survival were excluded as were publications using cohorts mixed with other surgical procedures.The articles generated from each search were collated,processed and then reported in accordance with PRISMA guidelines.All risk models were appraised for clinical credibility,methodological quality,performance,validation,and clinical effectiveness.RESULTS The initial search of composite databases yielded 8715 articles which reduced to 5827 following the deduplication process.After title and abstract screening,197 potentially relevant texts were retrieved for detailed review.Twenty-seven published studies were ultimately included which examined twenty-one multivariate risk models utilising exclusively preoperative data.Most models examined were clinically credible and were constructed with sound methodological quality,but model performance was often insufficient to prognosticate patient outcomes.Three risk models were identified as being promising in predicting perioperative mortality,including the National Quality Improvement Project surgical risk calculator,revised STS score and the Takeuchi model.Two studies predicted perioperative major morbidity,including the predicting postoperative complications score and prognostic nutritional index-multivariate models.Many of these models require external validation and demonstration of clinical effectiveness.CONCLUSION Whilst there are several promising models in predicting perioperative oesophagectomy outcomes,more research is needed to confirm their validity and demonstrate improved clinical outcomes with the adoption of these models.

Percutaneous closure of gastrorenal shunt as adjunctive therapy for esophageal carcinoma

The embolization of gastric varices is an established technique for acute bleeding in patients with portal hypertension. Here, we report an attempt to embolize a gastrorenal shunt to facilitate esophagectomy in a patient with an esophageal malignancy. To our knowledge, this is the first case in the literature to highlight the role of interventional medicine in the treatment of patients with esophageal malignancy.

Combined and intraoperative risk modelling for oesophagectomy:A systematic review

BACKGROUND Oesophageal cancer is the eighth most common malignancy worldwide and is associated with a poor prognosis.Oesophagectomy remains the best prospect for a cure if diagnosed in the early disease stages.However,the procedure is associated with significant morbidity and mortality and is undertaken only after careful consideration.Appropriate patient selection,counselling and resource allocation is essential.Numerous risk models have been devised to guide surgeons in making these decisions.AIM To evaluate which multivariate risk models,using intraoperative information with or without preoperative information,best predict perioperative oesophagectomy outcomes.METHODS A systematic review of the MEDLINE,EMBASE and Cochrane databases was undertaken from 2000-2020.The search terms used were[(Oesophagectomy)AND(Model OR Predict OR Risk OR score)AND(Mortality OR morbidity OR complications OR outcomes OR anastomotic leak OR length of stay)].Articles were included if they assessed multivariate based tools incorporating preoperative and intraoperative variables to forecast patient outcomes after oesophagectomy.Articles were excluded if they only required preoperative or any post-operative data.Studies appraising univariate risk predictors such as preoperative sarcopenia,cardiopulmonary fitness and American Society of Anesthesiologists score were also excluded.The review was conducted following the preferred reporting items for systematic reviews and meta-analyses model.All captured risk models were appraised for clinical credibility,methodological quality,performance,validation and clinical effectiveness.RESULTS Twenty published studies were identified which examined eleven multivariate risk models.Eight of these combined preoperative and intraoperative data and the remaining three used only intraoperative values.Only two risk models were identified as promising in predicting mortality,namely the Portsmouth physiological and operative severity score for the enumeration of mortality and morbidity(POSSUM)and POSSUM scores.A further two studies,the intraoperative factors and Esophagectomy surgical Apgar score based nomograms,adequately forecasted major morbidity.The latter two models are yet to have external validation and none have been tested for clinical effectiveness.CONCLUSION Despite the presence of some promising models in forecasting perioperative oesophagectomy outcomes,there is more research required to externally validate these models and demonstrate clinical benefit with the adoption of these models guiding postoperative care and allocating resources.

Palliation of Malignant Esophageal Obstruction and Fistulas with Metallic Stents: A Tertiary Center Experience

Background: To determine the usefulness of metallic stent in advanced oesophageal malignancies. Methods: In a retrospective study conducted at the Endoscopy Unit of King Abdulaziz University Hospital, patients underwent stent placement, with or without palliative radiotherapy for inoperable esophageal cancer, during the period spanning January 2010 through December 2014. Ethical approval for this study was granted by the King Abdulaziz University Research Ethics Committee. Data were collected from the electronic database of the hospital. All patients underwent OGD before stenting to know site of tumor, length of tumor and degree of stricture. Barium meal and CT scan was also done in some cases to know exact characteristics of tumor. Stent was selected more than 2 cm longer than the length of tumor. Self expanding metallic stents were used in all cases. Confirmation of proper placement of stent was done using fluoroscopy. Complications post stenting were analysed. Results: A total of 15 cases were studied. Males were 53.3% while females were 46.7%. Youngest patient was 39 yr old and eldest was 79 years with mean 64.93 years. Mean height was 159.73 cm and mean weight 54.98 kilogram. Co-morbidities like DM was 20%, DM with HTN was 6.7%, bronchial asthma 13.3% and DM with HTN with IHD and Renal implant in 6.7%. Diagnosis at admission was esophageal squamous cell carcinoma in 33.3%, esophageal adeno-carcinoma in 53.3%, gastric cancer in 6.7%, tracho-esophageal fistula in 6.7%. Stage 3 was 13.3%, and stage 4 was 86.7%. Surgical resection and palliation was done in14.2%, and only palliation was done in 92.9% of cases. SEMS were used in all patients and majority had Niti-S stent placed in 73.3% and Wallflex in 13.3% and Ultraflex in 6.7% and Boston in 6.7% cases. Dysphagia was Indication of stenting in 100% of cases and stricture in 57.1% and stricture and recurrent aspiration in 42.9%. Post stenting complications were early in 20% and late in 40%. Tumor ingrowth was in 20%, GERD in 20%, Mild chest pain and discomfort in 10%, stent migration in 10%, fistula formation in 10%, chest pain and GERD in 10%, and aspiration and pneumonia in 20%. Conclusions: Self expanding metallic stents are invaluable in advanced oesophageal cancer for palliation and alleviation of symptoms and better quality of life. Patients prior to chemoradiotherapy may get benefit of stenting making oesophageal passage patent which may otherwise get occluded by edema caused by radiotherapy.

Artificial intelligence in endoscopy:The challenges and future directions

Artificial intelligence based approaches,in particular deep learning,have achieved state-of-the-art performance in medical fields with increasing number of software systems being approved by both Europe and United States.This paper reviews their applications to early detection of oesophageal cancers with a focus on their advantages and pitfalls.The paper concludes with future recommendations towards the development of a real-time,clinical implementable,interpretable and robust diagnosis support systems.

用于预测食管癌新辅助治疗反应的转录组学生物标志物

食管癌是一种预后较差的致死性疾病,其死亡率排在恶性肿瘤第六位。证据表明,对于可手术切除的食管肿瘤,新辅助化疗和放化疗可以改善生存。遗憾的是,只有15%-30%的患者对新辅助治疗有反应,且常出现毒性反应。目前临床上尚无有效的预测标志物,无法对患者进行个体化治疗以显著改善疗效。本文对用于预测食管癌新辅助治疗反应的生物标志物的当前进展进行综述,并对生物标志物的研发所面临的挑战展开讨论。我们将这些问题与对生物标志物开发和报道的建议相联系进行探讨。目前大多数生物标志物研究集中在mRNA和miRNA,这些研究报道了涉及多条信号通路和生物学过程的诸多不同基因,很大程度上是由于不同的研究平台和不同的分析方法造成的。而且许多研究也因过于薄弱,不足以鉴定出可能的生物标志物。尽管多种食管癌分子亚型被提出,但其与临床结局的关系我们知之甚少。我们预测,未来几年随着基因组数据与临床试验协作研究成果的不断积累,对食管癌患者进行分层从而实现个体化治疗将成为可能。我们建议,未来生物标志物的研发应融入到精心设计的回顾性和前瞻性临床研究中。