Multidisciplinary approach for patients with esophageal cancer

Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett’s esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.     

Long-term survivors of advanced esophageal cancer without surgical treatment: a multicenter questionnaire survey in Kyushu, Japan

Since the introduction of recent improvements in adjuvant therapy for esophageal cancer, some patients have demonstrated good prognosis. In the present study, we analyzed 3- and 5-year survivors of advanced esophageal cancer who did not undergo any surgical treatment. Between 1990 and 1998, 831 patients were admitted to 14 university hospitals and one cancer center associated with the membership of the Kyushu study group for adjuvant therapy of esophageal cancer. Twelve (1.4%) of the patients were 3-year survivors and 13 (1.6%) were 5-year survivors. The reasons for non-operation were refusal (eight patients), tumor-related factors (11 patients), and host-related factors (six patients). With a single exception, all patients had locally advanced tumors. Almost all long-term survivors had fewer than five lymph node metastases, in regions limited to the neck and/or mediastinum. Radiation therapy was combined with chemotherapy for 16 of the 25 patients, and chemotherapy-based cisplatin was used for 15 of these 16 patients. Fifteen of the patients remain alive; 10 died seven of them from esophageal cancer. Chemoradiation therapy was effective for some patients with locally advanced esophageal cancer, particularly in the absence of or with few lymph node metastases. To improve the prognosis of patients with advanced esophageal cancer who, for various causes, cannot undergo surgical treatment, a new protocol for adjuvant therapy is required.     

Multidisciplinary therapeutic approach for maintaining long-term nutritional status for patient with advanced esophageal carcinoma confounded by dermatomyositis

We report a patient with advanced esophageal carcinoma associated with dermatomyositis who successfully maintained long-term good nutritional status by chemoradiation therapy and continuous enteral nutrition. A 64-year-old Japanese man was admitted to our hospital because of dysphagia and systemic edema. Because of debilitated status and malnutrition, intravenous corticosteroid infusion was first performed. Continuous enteral nutrition was performed through percutaneous endoscopic gastrostomy, and chemoradiation therapy was then performed. Although the endoscopic examination revealed complete regression of esophageal carcinoma, an esophagobronchial fistula was formed. The patient was periodically followed up by a multidisciplinary team for appropriate nutritional management; as a result, nutritional status was markedly improved and well maintained. A covered, selfexpandable metallic stent was placed in the esophagus to conceal the esophagobronchial fistula. This case highlights the importance of multidisciplinary therapeutic approach for maintaining good nutritional status and quality of life in patients with advanced esophageal carcinoma confounded by debilitating disorders.     

Preoperative therapy in locally advanced esophageal cancer

Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer(T2 or greater or node positive); however, a high rate of disease recurrence(systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment(preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy(radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.     

Utilization of surgery in trimodality‐eligible patients with locally advanced esophageal adenocarcinoma in a nonprotocol setting

Trimodality therapy with neoadjuvant chemoradiation followed by surgery significantly improves the survival of locally advanced (clinical stage IIA–III) esophageal cancer patients compared to treatment with surgery alone. This has resulted in an increased use of neoadjuvant therapy in recent years, yet little is known regarding how this increase has impacted the utilization of surgery in the treatment of locally advanced disease. Although previous reports of experimental protocols suggest that 90–95% of patients complete trimodality therapy including a surgical resection, trimodality therapy completion among adenocarcinoma patients eligible for curative resection has not been evaluated in a nonprotocol setting. We sought to (i) assess the completion of trimodality therapy among locally advanced esophageal adenocarcinoma patients; (ii) characterize the reasons for avoiding surgery; and (iii) identify factors associated with failure to complete trimodality therapy. We identified 296 patients with locally advanced esophageal adenocarcinoma eligible for trimodality therapy at our institution. All patients were evaluated in a multidisciplinary setting and considered eligible for curative resection after initial staging and physiologic assessment. Multivariable logistic regression was used to identify factors associated with failure to complete trimodality therapy. Of 296 trimodality‐eligible patients, 33% (97/296) did not complete trimodality therapy. Reasons for not undergoing surgery included patient choice (27.8%, 27/97), distant progression of disease during chemoradiation (23.7%, 23/97), and physician preference for surveillance (23.7%, 23/97). In addition, 17.5% (17/97) of patients had physical deterioration in performance status, and treatment‐related deaths occurred in 7.2% (7/97) prior to surgery. In the total study population (n = 296), multivariable logistic regression identified older age (≥70 years: odds ratio [OR] = 6.611, 95% confidence interval [CI]: 2.900–15.071), pretreatment standard uptake value (6.8–10.1: OR = 2.393, 95% CI: 1.050–5.455; ≥15.8: OR = 3.623, 95% CI: 1.604–8.186), and a radiation dose of 50.4 Gy (OR = 5.312, 95% CI: 2.365–11.929) as being significantly associated with failure to complete trimodality therapy. Among the subgroup of patients that successfully completed chemoradiation (n = 266), older patients (≥70 years: OR = 9.606, 95% CI: 3.637–25.372), those with a comorbidity score of 2 or higher (OR = 4.059, 95% CI: 1.257–13.103), and those that received a radiation dose of 50.4 Gy (OR = 4.878, 95% CI: 1.974–12.054) were at a significantly higher risk of not completing trimodality therapy. Trimodality therapy completion among patients with locally advanced esophageal adenocarcinoma in a nonprotocol setting is considerably lower than what has previously been reported in clinical trials. Our findings suggest that a selective approach to surgery is commonly utilized in clinical practice. Trimodality‐eligible patients that are older and have a higher comorbidity score are at risk for not completing trimodality therapy.     

Indications for chemotherapy in cancers of the esophagus, stomach and pancreas

During the last years the chemotherapy in osophageal, stomach and pancreatic cancer demonstrated some success. Radiochemotherapy for esophageal cancer is indicated as neoadjuvant therapy before surgery in locally advanced cancer or in patients with other diseases, which do not allow surgery. In stomach cancer patient there is a clear indication for chemotherapy in metastatic disease and within clinical trials as neoadjuvant chemotherapy in locally advanced cancer. In pancreatic cancer patient the chemotherapy shows less success comparing to other gastrointestinal cancer; it is part of the palliative concept with other therapeutic strategies.     

Neoadjuvant therapy for resectable esophageal cancer

BACKGROUND: Surgical excision remains the only therapeutic approach with curative potential in patients with localized esophageal cancer. Due to the presence of lymph node metastases upon diagnosis in a large percentage of patients with locally advanced tumors and/or the presence of considerable co-morbidity, only a limited number of patients are amenable to surgery. These facts have prompted us to evaluate approaches including perioperative therapy modalities. METHODS: By means of a computer-supported search (MEDLINE, ASCO Proceedings) as well as a manual literature search, randomized clinical trials and meta-analyses evaluating preoperative therapy plus surgery in patients with resectable esophageal cancer were identified. RESULTS: Twenty-three randomized clinical studies and five meta-analyses were identified. Interpretation--especially of the older studies--however, is hampered by the lack of a stringent application of modern examination techniques allowing for exact specification of tumor stage (resectable/locally advanced) as well as the inclusion of patients with different histological entities (squamous cell/adenocarcinoma), different surgical techniques and the low number of patients. There were no significant differences for the following perioperative therapy modalities regarding tumor-related mortality: preoperative radiotherapy versus postoperative radiotherapy, preoperative and postoperative radiotherapy versus postoperative radiotherapy (higher mortality in preoperative and postoperative radiotherapy arm), preoperative radiotherapy versus surgery, preoperative chemotherapy versus surgery, preoperative and postoperative chemotherapy versus surgery. In terms of 3-year mortality, statistically significant differences could be found for the following therapy modalities: preoperative radiochemotherapy versus surgery (preoperative therapy superior), preoperative chemotherapy versus preoperative radiotherapy (preoperative radiotherapy superior). CONCLUSION: Judging from these data, no clear recommendation for a standard multimodality approach outside clinical studies can be given for patients with resectable esophageal cancer. Neoadjuvant therapy, therefore, can only be recommended in centers with a maximum surgical expertise and in the context of multidisciplinary study protocols.     

Multidisciplinary management of gastric and gastroesophageal cancers

Carcinomas of the stomach and gastroesophageal junction are among the five top leading cancer types worldwide. In spite of radical surgical R0 resections being the basis of cure of gastric cancer, surgery alone provides long-term survival in only 30% of patients with advanced International Union Against Cancer （UICC） stages in Western countries because of the high risk of recurrence and metachronous metastases. However, recent large phase-Ⅲ studies improved the diagnostic and therapeutic options in gastric cancers, indicating a more multidisciplinary management of the disease. Multimodal strategies combining different neoadjuvant and/or adjuvant protocols have clearly improved the gastric cancer prognosis when combined with surgery with curative intention. In particular, the perioperative （neoadjuvant, adjuvant） chemotherapy is now a well-established new standard of care for advanced tumors. Adjuvant therapy alone should be carefully discussed after surgical resection, mainly in individual patients with large lymph node positive tumors when neoadjuvant therapy could not be done. The palliative treatment options have also been remarkably improved with new chemotherapeutic agents and will further be enhanced with targeted therapies such as different monoclonal antibodies. This article reviews the most relevant literature on the multidisciplinary management of gastric and gastroesophageal cancer, and discusses future strategies toimprove Iocoregional failures.     

Surgery for locally advanced disease

Locally advanced prostate cancer is diagnosed in approximately one in four new cases of prostate cancer. The estimated disease-specific mortality rate resulting from monotherapy with either surgery or radiotherapy is a disappointing 75%. A multimodality treatment approach could offer more promising results. In addition, several key factors related to surgical treatment of locally advanced prostate cancer may optimize the oncologic results and minimize patient morbidity. In this report, we summarize some of the anatomic features and technical concepts associated with the surgical management of this disease and review recently published results of the outcomes of surgery and neoadjuvant or adjuvant chemohormonal therapy for locally advanced prostate cancer.     

Down syndrome and esophageal cancer

We present two cases of Down syndrome with inoperable esophageal cancer at a relatively young age. The first patient had a locally advanced squamous cell carcinoma of the distal esophagus. The second had a short circular adenocarcinoma of the distal esophagus with peritoneal and liver metastases. The cases are discussed with regard to the current literature on Down syndrome and esophageal cancer.     

Recent progress in perioperative management of patients undergoing esophagectomy for esophageal cancer

Esophagectomy remains the mainstay of curative intent treatment for esophageal cancer. Oncologic esophagectomy is a highly invasive surgery and both morbidity and mortality rates still remain high. Recently, it has been revealed that multidisciplinary perioperative management can decrease the postoperative complications after esophagectomy. In this review, we summarized the recent progress in each component of multidisciplinary perioperative care bundle, including oral hygiene, cessation of smoking and alcohol, respiratory training, measurement of physical fitness, swallowing evaluation and rehabilitation, nutritional support, pain control and management of delirium. The accumulation of evidence and the popularization of knowledge will increase safety of esophagectomy and thus improve the outcome of patients with esophageal cancer.     

Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis

Esophageal squamous cell cancer (ESCC) is a high‐grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5‐Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time‐to‐event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan–Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long‐term outcomes compared with FP‐based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.     

Endoscopic ultrasound restaging after neoadjuvant chemotherapy in esophageal cancer

BACKGROUND: The role of endoscopic ultrasound (EUS) to evaluate treatment response postneoadjuvant therapy for restaging esophageal cancer prior to surgical resection is uncertain. Accuracy of EUS is lower but potential to predict response to chemoradiation indicates that EUS may be helpful prior to surgery. OBJECTIVE: To determine staging accuracy of EUS after neoadjuvant chemotherapy, predictors of tumor response, and survival in locally advanced esophageal cancer. METHODS: Single-center retrospective evaluation of patients with locally advanced esophageal cancer on a prospective chemotherapy study. Patients who underwent EUS without FNA pre- and postchemotherapy were included. RESULTS: A total of 49 patients (43 men and 6 women) were evaluated with EUS pre- and postneoadjuvant chemotherapy. Forty-seven patients had tumor localized at the GE junction and two had mid-esophageal lesions. The median survival time was 53 months. Tumor and nodal staging accuracy postchemotherapy were 60% (27 of 45). T-stage accuracy postchemotherapy was superior in patients without a response to chemotherapy (95.7%vs 26.1%, p<0.0001). More than 50% in reduction of tumor thickness postchemotherapy was associated with tumor downstage and better survival. N0 disease on final pathology was the best predictor of improved survival. CONCLUSION: Accuracy of EUS postchemotherapy is lower than initial staging accuracy; therefore the ability to predict downstaging based on EUS is marginal. Pathology N1 disease postchemotherapy is the best predictor of survival. EUS staging postneoadjuvant chemotherapy should focus on improving nodal staging accuracy with FNA.     

Neoadjuvante und adjuvante Therapie des Magen- und ?sophaguskarzinoms

The prognosis of locally advanced gastric and oesophageal cancers is poor, but it has been shown that multimodal treatment can lead to better outcomes than surgery alone. Two randomised studies conducted in Europe have shown that perioperative chemotherapy does significantly improve the survival of patients with adenocarcinoma of the stomach and oesophagogastric junction. These results have had a profound effect on the treatment of patients presenting with stage II or stage III disease. Because of the results of recent meta-analyses, patients with locally advanced adenocarcinomas of the oesophagus receive neoadjuvant chemotherapy or chemoradiation therapy. Squamous cell cancer of the oesophagus is treated with chemoradiation. Secondary resection is optional. Patients with locally advanced gastric and oesophageal cancer should always be referred to an experienced high-volume centre where findings are discussed by a multidisciplinary tumour board. It has been demonstrated that outcomes are better when such patients are treated in designated centres.     

Survival outcomes of resected patients who demonstrate a pathologic complete response after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer

A variety of strategies, using chemotherapy, radiation therapy, and surgical resection have been employed in the treatment of locally advanced esophageal cancer. No strategy has proven superior, and poor long-term survival is anticipated. A survival benefit has been suggested for patients who achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation therapy. We examined the collective results at three institutions of patients who achieved a pCR following neoadjuvant chemoradiation therapy. A retrospective, chart-based review was conducted. Kaplan-Meier calculations were used to determine overall and disease-free survival. Between 1995 and 2002, 229 patients were treated with neoadjuvant chemoradiation followed by surgery as a planned approach for locally advanced esophageal cancer. Forty-one patients (18%) demonstrated pCR and were the focus of this study. Histology was adenocarcinoma in 29, squamous in 10, and adenosquamous/undifferentiated in two patients. Forty patients were staged by endoscopic ultrasound prior to neoadjuvant therapy and all demonstrated a T-stage of 2 or higher, while 19 had evidence of nodal metastasis. Four patients died in the perioperative period. The remaining patients have been followed for an average of 46 months. Overall survival at 5 years was 56.4% and a median survival has not been reached. Esophageal cancer patients who demonstrate a pCR following neoadjuvant chemoradiation are a select subset who demonstrate excellent long-term survival. Identification of clinical variables or biomarkers predictive of pCR may therefore optimize treatment strategies of patients with locally advanced esophageal cancer.     

Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer. METHODS: Patients with T3-4 and NO-1 esophageal carcinoma from a number of institutions were non-randomly, prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m~2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m~2 and 5-fluorouracil 1000 mg/m~2 for five consecutive days), or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-totreat patients' outcome of survival. RESULTS: A total of 60 patients (n=30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematologicai and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI, 27.5-36.4 vs 15.2-26.1) and 3-year survival (70.0% vs 33.7%; P=0.003). Low histological grade of tumor (P<0.001) was associated with favorable survival in these locally advanced patients. CONCLUSION: For locally advanced esophageal cancer, the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.     

Current management of locally advanced pancreatic cancer

Almost 30% of patients with pancreatic cancer present with large, locally advanced tumors in the absence of distant metastases. Because surgical resection is frequently contraindicated by vascular invasion, locally advanced pancreatic cancer has a dismal prognosis with a 6-10-month median survival. Recent advances in the multimodality treatment of other gastrointestinal malignancies have not altered the management of patients with locally advanced pancreatic cancer, a clinical dilemma reflected by the number of nonrandomized trials and anecdotal reports addressing this difficult disease. Our review summarizes the current status of aggressive surgical resection and neoadjuvant chemoradiation for locally advanced pancreatic cancer and suggests a treatment algorithm for patients with this disease based upon published clinical evidence.     

Surgery provides improved overall survival in surgically fit octogenarians with esophageal cancer after chemoradiation therapy

BackgroundMultiple randomized controlled trials have shown that multimodal therapy provides the best overall survival for patients who had locally advanced esophageal cancer. However, it is unknown if multimodal therapy offers the best overall survival in octogenarians.MethodsWe performed retrospective cohort study using data obtained from the National Cancer Database (NCDB) for octogenarians who had locally advanced esophageal cancer from 2004 to 2015. We evaluated the 5-year overall survival for patients among different therapies. We compared the 5-year overall survival between patients receiving chemoradiation therapy followed by surgery and a propensity-matched group of patients who underwent chemoradiation only.ResultsThere were 21,710 octogenarians (15%) with esophageal cancer in the NCDB database. Among octogenarians, there were 6,960 patients (32%) who had clinical stage II–III esophageal cancer. Among 6,922 patients whose treatment data were available, the most common therapy was chemoradiation (n=3,360, 49%). Two of the most common therapies that included surgical resection were surgery only (n=314, 5%) and chemoradiation therapy followed by surgery (n=172, 2%). Among different treatments, the best 5-year overall survival was achieved in patients receiving chemoradiation therapy followed by surgery (P<0.001). In the propensity score-matched cohort between chemoradiation therapy followed by surgery (n=83) to chemoradiation therapy only (n=83), there was an association with improved 5-year overall survival in the patients who had chemoradiation therapy followed by surgery (17.9%) compared to the patients who underwent chemoradiation only (5.7%, P=0.003).ConclusionsMost octogenarians with locally advanced esophageal cancer underwent definitive chemoradiation therapy. Very few patients underwent chemoradiation followed by surgery; however, the multimodality treatment provided increased overall survival. Surgically fit octogenarians should be considered for chemoradiation therapy followed by surgery.     

Safety and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer: a propensity score matching

Esophagus - This study aims to investigate the efficacy and feasibility of esophagectomy following combined neoadjuvant immunotherapy and chemotherapy for locally advanced esophageal cancer. We...     

MDT lung cancer care: Input from the Surgical Oncologist

Although there have been many advancements in the multidisciplinary management of non‐small cell lung cancer (NSCLC), surgery remains the primary modality of choice for resectable lung cancer when the patient is able to tolerate lung resection physiologically. There have been recent advances in surgical diagnosis and treatment of lung cancer. Increasing use of low‐dose computed tomography (CT) screening for lung cancer has resulted in increased detection of small peripheral nodules or semi‐solid ground glass opacities. Here, we review different modalities of localization techniques that have been used to aid surgical excisional biopsy when needle biopsy has failed to provide tissue diagnosis. We also report on the current debates regarding the use of sublobar resections for Stage I NSCLC as well as the surgical management of locally advanced NSCLC. Finally, we discuss the complex surgical management of T4 NSCLC lung cancers.