Multimodality Approaches for the Curative Treatment of Esophageal Cancer

Authors: Raymond Jang MD, MSc, FRCPCa, Gail Darling MD, FRCSCa, and Rebecca K.S. Wong MBChB, MSc, FRCPCa
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  • a From the Departments of Medical Oncology, Thoracic Oncology, and Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Carcinoma of the esophagus and gastroesophageal junction tumors presenting with locoregional disease are potentially curable, although the cure rate is modest. Many different treatment approaches have been studied, with a multimodality approach associated with a 10% to 15% greater survival advantage compared with a single-modality approach. A systematic review was conducted to address 3 clinical questions: whether patients with resectable esophageal cancer should receive preoperative versus postoperative therapy, how to choose between these options, and whether surgery be avoided in patients who are candidates for both definitive chemoradiotherapy and definitive combined modality therapy. Recommendations from 3 recent treatment guidelines from Ontario, NCCN, and Belgium were consulted to address these questions.

NCCN: Continuing Education

Accreditation Statement

This activity has been designated to meet the educational needs of physicians and nurses involved in the management of patients with cancer. There is no fee for this article. No commercial support was received for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians.

NCCN designates this journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

This activity is accredited for 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/60896; and 4) view/print certificate.

Release date: February 18, 2015; Expiration date: February 18, 2016

Learning Objectives

Upon completion of this activity, participants will be able to:

  • Discuss the clinical evidence supporting the use of combined modality therapy for localized carcinoma of the esophagus and GEJ
  • Summarize the recommendations outlined in the clinical practice guidelines for the management of patients with localized resectable esophageal and GEJ

Background

Carcinoma of the esophagus is the eighth most common cancer worldwide, with approximately 496,000 cases in 2015.1 The incidence varies globally, with approximately 80% of cases occurring in less developed countries.1 Although the survival rate has been slowly improving in the United States by approximately 0.7% each year from 2002 to 2012, likely because of multimodality strategies and improved supportive care, the survival rate remains modest at 20% at 5 years.2 The optimal choice of treatment strategy must be individualized, however, based on patients’ disease distribution and comorbidities. Furthermore, the use of radical approaches may be justified for selected recurrent disease, providing a second opportunity for cure.

The discussion regarding management of the gastroesophageal junction (GEJ) is arguably one of the most challenging. In 2010, the 7th edition of the Union for International Cancer Control (UICC) TNM staging system provided clarification for the classification of junctional tumors. Specifically, tumors with an epicenter within 5 cm of the GEJ and extend into the esophagus should be classified and staged using the esophageal system.3 The extent of involvement and the distribution of the lymphatics at risk likely play an important role in the optimal design of surgical and radiotherapy techniques. Randomized trials dedicated to GEJ tumors are rare,4 although several groups are working to fill this gap (ClinicalTrials.gov identifiers: NCT02193594 and NCT01523015). Until a robust body of literature dedicated to GEJ tumors is available, one must draw from the literature on esophagus and gastric cancers that includes GEJ tumors.

The behavior of different histologic subtypes is a major factor influencing the consideration of optimal strategies. Historically, squamous cell carcinoma (SCC) and adenocarcinomas are assumed to behave similarly, and are therefore analyzed and considered as one group. More contemporary thinking would advocate for these to be considered as different diseases in terms of origin, cellular characteristics, and responsiveness to treatments.

This article addresses 3 contemporary questions in the decision-making process regarding the multimodality treatment of esophageal cancer with curative intent: whether patients with resectable esophageal cancer should receive preoperative or postoperative therapy along with surgery, how to choose between these options, and whether surgery can be avoided in candidates for both definitive chemoradiotherapy and definitive combined modality therapy with surgery.

This article does not replicate the work of the large number of systematic reviews or clinical practice guidelines5 that exist for the management of esophageal cancer. Rather, it focuses on the more recent literature and how it has shaped current thinking. For clarity, the authors classified the studies into esophageal or gastric trials based on which primary constitutes the majority being enrolled into the trial.

Methods

A search of the Standards and Guidelines Evidence (SAGE) database5 using the term “esophageal” identified 15 guidelines; 3 of the most up-to-date guidelines (since 2012) and the authors’ own interpretation and experiences were used to shape the present discussion. The 3 guidelines are produced by Cancer Care Ontario’s Program in Evidence-Based Care (CCO PEBC),6,7 NCCN,8 and Belgian Health Care Knowledge Centre (KCE reports 179A).9 The CCO PEBC guideline6 has the highest Appraisal of Guidelines for Research and Evaluation (AGREE) score (designed to measure the quality of guidelines).10 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) document evidence-based, consensus-driven management and provide recommendations based on the best evidence available at the time they are derived.8 The Belgian guidelines used the Grading of Recommendations Assessment, Development and Evaluation (GRADE)11 methodology and nomenclature to arrive at their recommendations. The Belgian and NCCN Guidelines contained considerations for the management of recurrent disease that are not within the scope of the CCO PEBC guideline.9

A systematic review approach was used. The authors conducted an updated version of the literature search used by CCO PEBC Evidence-Based Series 2-11. The identical search strategy used for Medline was applied (performed in August 2014).6 Only randomized trials and systematic reviews were used to provide the evidence base. Recommendations from the 3 guidelines mentioned previously were consulted to inform this discussion.

Results

The CCO PEBC guideline identified 58 randomized trials (Table 1) and 16 meta-analyses and systematic reviews. In the 2014 search, 2 additional randomized trials12,13 and 7 meta-analyses and systematic reviews were identified.1420

Preoperative Versus Postoperative Therapy

The overall poor prognosis of advanced esophageal cancer has motivated multiple strategies in an effort to improve outcomes, including preoperative chemoradiotherapy, preoperative and perioperative chemotherapy, definitive chemoradiotherapy, and postoperative chemoradiotherapy. This section discusses the key trials and meta-analyses of each of these approaches.

Preoperative Chemoradiotherapy: A total of 15 randomized trials investigating preoperative chemoradiotherapy were identified.12,2134 The 2 most recent trials included the pivotal CROSS trial published by van Hagen et al30 in 2012 and FFCD 9901 reported by Marriette et al12 in 2014.

Multiple systematic reviews conducted before 2012 had already concluded that trials addressing this strategy were similar enough to warrant a meta-analysis approach and showed a survival advantage at 3 years.3537 A 2011 meta-analysis, the first

Table 1

Esophageal Trials

Table 1
to include preliminary results from the CROSS trial, further consolidated the survival benefit of preoperative chemoradiotherapy over surgery alone (hazard ratio [HR], 0.78; 95% CI, 0.70–0.88; P<.0001), corresponding to an absolute survival benefit of 8.7% at 2 years.38 More recent meta-analyses supported these findings.14,18,19 A meta-analysis on toxicities did not find a significant difference in perioperative morbidity or mortality, although subgroup analysis suggested an effect in patients with squamous cell histologies.15

The pivotal CROSS30 trial enrolled 366 patients, representing the largest single-study trial of preoperative chemoradiotherapy versus surgery alone; 75% had adenocarcinomas and 23% had GEJ tumors. Patients with clinical stage T1N1 or T2–3N0–1 disease were eligible, and were randomized to either 41.4 Gy of radiotherapy over 5 weeks with concurrent weekly carboplatin (area under the curve, 2) and paclitaxel (50 mg/m2) followed by surgery, or to surgery alone. Pathologic complete response was seen in 29% of patients. Overall survival (OS) was better in the preoperative chemoradiotherapy group with an HR of 0.657 (95% CI, 0.495–0.871; P=.003). At 5 years, the OS benefit was 13% (47% vs 34%). Chemoradiotherapy was associated with fewer locoregional recurrences and distant and peritoneal metastases.39

In contrast to the CROSS trial, the most recent trial, FFCD 9901,12 was closed early (after enrolling 195 patients) because of futility and deserves further discussion. FFCD 9901 randomized patients with early-stage (stages I and II) esophageal cancer to either neoadjuvant chemoradiotherapy followed by surgery (45 Gy in 25 fractions over 5 weeks with 2 cycles of concomitant chemotherapy composed of fluorouracil, 800 mg/m2 and cisplatin, 75 mg/m2) or to surgery alone. Most (70%) had SCC histology. Kaplan-Meier OS curves for the 2 arms crossed, with the surgery arm being superior before 4 years of follow-up and the combined modality arm being superior afterwards. It is likely that the higher rates of postoperative mortality observed in this trial (11.1% in the combined modality arm vs 3.4% in the surgery-alone arm; P=.049) offset the effects of the lower recurrence rates in the trimodality arm (28.6% vs 44.3%, respectively; P=.02). Alternatively, it is possible that the potential gain achievable in patients with earlier-stage esophageal cancer is modest.12,40

When these results are considered together, for patients who fit the eligibility criteria for the CROSS trial, trimodality treatment is expected to provide a survival benefit and is a suitable treatment strategy.

Preoperative and Perioperative Chemotherapy: Preoperative and perioperative chemotherapy strategies could be considered together. The intensity of the chemotherapy delivered preoperatively in these trials is similar (eg, 2–3 cycles), and in many studies, the proportion of patients completing the postoperative portion of the regimen is limited, with the latter finding suggesting much of the benefit from the perioperative strategy may be attributable to the preoperative component.

Sjoquist et al38 published the most recent meta-analysis on preoperative chemotherapy trials in esophageal cancers and showed an improved survival, with an HR of 0.87 (95% CI, 0.79–.96; P=.005). Similarly, a recent Cochrane review also supported these conclusions.17

Eleven randomized trials21,4150 compared preoperative chemotherapy with surgery alone, whereas only 3 authors evaluated the benefit of perioperative chemotherapy.5153

Although collectively, perioperative “esophagus” chemotherapy trials would support the efficacy of this treatment modality, heterogeneity between trials has limited its effect on current practice. A trial reported by Roth et al51 in 1988 included only 36 patients and was therefore too small to inform practice. Two more recent studies were more adequately powered. A US Intergroup effort (RTOG 8911, US Intergroup 113) reported by Kelsen et al50,52 in 2007 recruited 467 patients. A French study reported in 2011 by Ychou et al53 enrolled 224 patients. The interventions were similar, with both trials using cisplatin and fluorouracil. The results of these 2 trials were opposing, with the US study showing no benefit, whereas the French result showed positive results. The larger proportion of advanced cancers in the US trial (weight loss of >10% at diagnosis was 23% and R0 resection was achieved in 60%) may have contributed to the differences.

In contrast, the single perioperative chemotherapy “gastric” trial, which included a significant component of lower esophagus or GEJ adenocarcinomas (25%), was influential in changing practice. This study showed an OS benefit with perioperative chemotherapy versus surgery alone (5-year OS of 36% vs 23%).54

Preoperative and perioperative chemotherapy are reasonable alternative choices for patients with resectable esophageal cancer. A perioperative approach is supported by more contemporary evidence as was presented in this section.

Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy in Adenocarcinomas: Decision-making between these 2 established strategies remains controversial in practice. Although 2 randomized trials attempted to clarify this debate, they failed to provide clear guidance.4,55

Stahl et al4 conducted the only phase III trial comparing these strategies. Also referred to as the POET trial, this study enrolled 126 patients with approximately equal proportions of Siewert I and II/III adenocarcinoma of the GEJ. The study was discontinued early because of poor accrual. Although the proportion of patients who experienced a complete response was higher among those treated with preoperative chemoradiotherapy (15.6% vs 2.0%), the rate of local recurrence was lower in those treated with preoperative chemoradiotherapy (59.0% vs 76.5%; P=.06), and the absolute survival rate favored preoperative chemoradiotherapy (3-year OS, 47.7% vs 27.7%), these results did not reach statistical significance.

In a phase II trial of 75 patients with adenocarcinoma of the esophagus and GEJ (<2 cm) randomized to either preoperative chemotherapy or preoperative chemoradiotherapy, Burmeister et al55 reported no difference in survival, although improvement in margin involvement was seen with the addition of radiotherapy.

In the absence of robust data, the choice of strategy must be guided by practical and morbidity considerations. Preoperative chemoradiotherapy involves a shorter overall treatment time, while eliminating the need to consider delivering treatment after surgery, which has been shown to be challenging in multiple studies. The extent of the tumor, especially in the craniocaudal direction, may expose a significant amount of the lung and heart to significant doses of radiotherapy. Preoperative chemotherapy may be favored when nodal involvement expands the target volume or in the presence of significant primary tumor length. In fact, the inclusion criteria for the CROSS trial limited the length and width of the primary tumor to 8 cm.30 The risk of pulmonary toxicities deserve consideration, especially when combining paclitaxel chemotherapy with radiotherapy in patients with more extensive target volumes.

In contrast, for patients with significant lateral involvement, a significant downstaging effect may be particularly desirable to enhance the ability to achieve an R0 resection. Intermediate end points, such as R0 resection rates and pathologic complete response rates, would suggest an advantage with preoperative chemoradiotherapy in these settings. Finally, gastroesophageal tumors that extend significantly into the stomach would suggest a higher pattern of nodal spread more similar to proximal gastric cancers. However, the radiotherapy portals used in the existing trials are designed to capture periesophageal nodes. The relative value and toxicity profile associated with treatment volumes that include upper abdominal nodes is uncertain, although the ongoing TOPGEAR trial should provide data to guide practice (ClinicalTrials.gov identifier: NCT01924819). These factors should be considered when selecting between these 2 modalities in the management of adenocarcinomas of the esophagus and GEJ.

Taken together, rationale exists to favor the use of preoperative chemoradiotherapy as the preferred approach, switching to perioperative chemotherapy when some of the relevant factors would predict for incremental toxicities with radiotherapy.

Postoperative Chemoradiotherapy, Preoperative or Postoperative Radiotherapy, or Postoperative Chemotherapy: The landmark INT-0116 trial showed that postoperative chemoradiotherapy is a valid option for patients with GEJ adenocarcinomas (3-year OS rate of 50% vs 41% with surgery alone).56,57

No trials involving mostly patients with esophageal cancer or patients with squamous cell histology have compared postoperative chemoradiotherapy with surgery alone. Postoperative chemoradiotherapy is not a recommended option for patients with esophageal cancers that are above the GEJ.

Neither preoperative nor postoperative radiotherapy (without chemotherapy) are used because of the lack of survival benefit.58,59 Similarly, there is lack of data to support adjuvant chemotherapy. Only a few trials have been performed, and results have been negative. One trial of adjuvant chemotherapy using cisplatin and fluorouracil60 showed only a trend toward an OS benefit (5-year OS rate of 61% vs 52%; P=.13) favoring adjuvant therapy. The patients were Japanese with SCC histology, and adjuvant therapy consisted of 2 cycles of cisplatin and fluorouracil.

Recommendations: The Ontario guidelines panel recommended the use of preoperative platinumbased chemotherapy plus radiotherapy as the preferred modality for the management of surgically resectable patients with esophageal cancer.6 It also recommended preoperative platinum based chemotherapy alone as an alternative choice.

NCCN Guidelines cite category 1 evidence that combined modality therapy is effective for patients with localized esophagogastric cancer.8,54,56,61 Recommendations emphasize the importance of an infrastructure that encourages multidisciplinary treatment decision-making, with specific emphasis on composition of the tumor boards, regular meetings to facilitate decision-making, joint review of data, and the need for documentation of tumor board discussions.

The Belgian guidelines panel indicated in their recommendations that, if after multidisciplinary discussion neoadjuvant treatment is considered for a locally advanced esophageal or junction tumor, neoadjuvant chemoradiotherapy is preferred (strong recommendation, low level of evidence).9 In terms of adjuvant treatment, this is not routinely recommended (strong recommendation, low level of evidence).6

These recommendations can be considered consistent among 3 large practice communities in the interpretation of the evidence and approach to neoadjuvant therapy, while each emphasizes a different aspect of choice between the available options. The authors’ practice approach generally favors neoadjuvant chemoradiotherapy, but selectively favors perioperative chemotherapy for adenocarcinomas when radiotherapy use is expected to be associated with increased toxicities.

In Patients Who Are Candidates for Both Definitive Chemoradiotherapy and Combined Modality Therapy With Surgery, Can Surgery Be Avoided?

Definitive chemoradiotherapy and combined modality with surgery are both curative options used widely in clinical practice. Historically, patients selected for a nonsurgical approach to cure are typically those with significant comorbidities or who express a strong preference against surgery. However, with advances in surgical techniques and perioperative support, advanced biological age is not necessarily a contraindication to surgery, and emerging evidence may suggest that surgery can be avoided in squamous histologies. This section discusses the evidence for definitive chemoradiotherapy strategies with or without surgery.

Definitive Chemoradiotherapy: Definitive chemoradiotherapy is the preferred treatment for those with unresectable disease or a contraindication to surgery, especially those with SCC. A 2003 Cochrane review found that combined chemoradiotherapy led to an absolute mortality difference of 7% at 2 years compared with radiation alone.62

RTOG 85-01 compared a higher dose of radiotherapy (64 Gy in 32 fractions over 6.5 weeks) alone with a lower dose (50 Gy in 25 fractions over 5 weeks) combined with chemotherapy on weeks 1 and 5 (infusional fluorouracil, 1000 mg/m2 per day on days 1 to 4, with cisplatin, 75 mg/m2 on day 1). The chemoradiotherapy group also received 2 further cycles of cisplatin and fluorouracil on weeks 8 and 11.63 Long-term follow-up showed that 5-year survival was 26% for the chemoradiotherapy and 0% for the radiotherapy arm.61 A follow-up trial (INT 0123) showed that a higher dose of radiotherapy (64.8 Gy) with chemotherapy was not superior in terms of survival or disease control than a lower dose (50.4 Gy) with chemotherapy, but was more toxic.64 The chemotherapy was the same on both arms (cisplatin and fluorouracil), as well as in the earlier RTOG 85-01 trial (although in the latter, all chemotherapy was delivered in 4-week cycles). Therefore, chemoradiation (50 Gy in 25 fractions with cisplatin and fluorouracil) represents the standard definitive dose protocol. Patients who tolerate chemoradiation well should be considered for 2 more cycles of adjuvant chemotherapy as per the landmark trials, with the knowledge that many patients will not be eligible because of toxicity and poor performance status by the end of chemoradiation.

Cisplatin and fluorouracil represent the mainstay choice of chemotherapy, although other choices have been studied. Survival rates with FOLFOX-based radiotherapy were similar to cisplatin and fluorouracil-based radiotherapy, but with a differing side effect profile (more neuropathy but less renal dysfunction and mucositis with FOLFOX).65 Another chemotherapy regimen used with definitive-dose radiotherapy consists of carboplatin and taxol. A phase II study of patients with locally unresectable esophageal cancers (T4N0–1) used 50.4 Gy of radiotherapy along with carboplatin and paclitaxel, as in the CROSS protocol, and showed 2- and 3-year survival rates of 32% and 16%, respectively, with a reasonable side-effect profile.66 Experience with definitive chemoradiation using carboplatin and paclitaxel has been published by other centers.67,68

Definitive Chemoradiotherapy Versus Surgery: Teoh et al13 reported on a small randomized trial performed in Asia on patients with SCC (N=81); most patients had advanced disease (62% T3, 52% N1), although the R0 resection rate was high (86.4%). With a median follow-up of 93 months, the group reported a 5-year OS of 29% with surgery alone versus 50% with chemoradiotherapy alone, although these results were not statistically significant (P=.147). The same trend was seen in cause-specific and disease-free survivals.

Preoperative Chemoradiotherapy Versus Definitive Chemoradiotherapy: Two trials comparing preoperative chemoradiotherapy followed by surgery versus definitive chemoradiotherapy have been conducted (almost) exclusively with SCC histology.69,70

The German trial, exclusively for SCC histology, used induction chemotherapy (fluorouracil, leucovorin, etoposide, and cisplatin for 3 cycles), followed by chemoradiotherapy (40 Gy with cisplatin and etoposide), followed by either surgery or further radiotherapy (for a total radiotherapy dose of at least 65 Gy).69 The French trial, with 89% of patients with SCC histology, used either split-course radiotherapy (30 Gy) or standard radiotherapy (total of 46 Gy) with 2 cycles of cisplatin and fluorouracil. Only those who experienced a response after induction chemotherapy were randomized: half to further chemoradiation and the other half to surgery.70 Both trials were designed to be equivalence trials, with a delta of 15%69 and 10%,70 respectively.

The OS at 2 years was similar in both arms of the French and German trials (39.9% and 33.6%, respectively, for preoperative chemoradiotherapy; and 35.4% and 39.8%, respectively, for chemoradiotherapy alone). The local control rate at 2 years was better with surgery in both trials (66.7% for preoperative chemoradiotherapy vs 57.0% for chemoradiotherapy in the French trial, and 64.3% for preoperative chemoradiotherapy vs 40.7% for chemoradiotherapy in the German trial), although treatment-related mortality was also higher with surgery.

The role of salvage surgery in the nonsurgical arms was not detailed but requires consideration in clinical practice. Ariga et al31 reported on the role of salvage surgery in a group of matched patients who were surgical candidates but opted to undergo definitive chemoradiotherapy. OS was better in the chemoradiotherapy-alone arm, with only 26% of patients undergoing salvage esophagectomy (5-year OS rate was 75% with chemoradiotherapy vs 51% with surgery alone).

Given the somewhat atypical regimens used in these trials compared with the more commonly used chemoradiotherapy regimens, and the relatively large delta that was used, challenges exist in interpreting and translating these observations into practice.

In patients with squamous cell histologies, as was included in these trials, chemoradiotherapy alone with careful follow-up and consideration of salvage surgery may be a good strategy for those who attain a clinical complete response. This is particularly true if survival and morbidity are the dominant factors influencing decision-making. The optimal strategy to evaluate response and schedule of follow-up require further investigation, although a combination of CT and endoscopy at regular intervals could be reasonable. No data are available to address this approach in adenocarcinoma.

Recommendations: The CCO guidelines suggest that in patients with SCCs, in whom a greater operative risk is anticipated, the adoption of a nonsurgical approach is favored based on the data.

NCCN Guidelines recommend the use of definitive chemoradiotherapy for T4b (unresectable) tumors in medically fit and unfit patients and for resectable tumors (T1bN+, T2–4aN0-N+) in medically unfit patients. In medically fit patients with resectable tumors (T1bN+, T2–4aN0-N+), definitive chemoradiotherapy is only recommended for cervical SCC esophageal cancers, and for patients with adenocarcinomas it is only recommended for those who decline or cannot withstand surgery.8

The Belgian guidelines recommend that definitive concomitant chemoradiotherapy be considered in patients with locally advanced esophageal cancer of any histologic type if the tumor is unresectable or the patient is unfit for or declines surgery (strong recommendation, moderate level of evidence). Use of definitive concomitant chemoradiotherapy in patients who have resectable disease should be restricted to clinical studies (strong recommendation, moderate level of evidence).

When these guidelines are considered together, consensus exists that multimodality therapy including surgery is the recommended treatment for patients with resectable disease. Use of definitive chemoradiotherapy without surgery is still controversial but has become a part of standard practice, with close monitoring after clinical complete response. Clinical trials addressing this area should be a priority.

Conclusions

For patients with locoregional cancer, preoperative platinum-based chemotherapy plus radiotherapy is the preferred modality for the management of surgically resectable esophageal cancer. Preoperative cisplatin-based chemotherapy is an alternative choice. Chemoradiotherapy alone, reserving surgery for incomplete response, holds promise for providing an organ-preserving approach while minimizing treatment-related toxicities for SCC. Thoughtful multidisciplinary deliberations and clinical trials are the cornerstone for determining the optimal multimodality strategy best suited to each patient.

The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. This work was supported by the Esophageal Cancer Research Fund and the Princess Margaret Cancer Centre, Foundation.

EDITOR

Kerrin M. Green, MA,Assistant Managing Editor, JNCCN—Journal of the National Comprehensive Cancer Network

Ms. Green has disclosed that she has no relevant financial relationships.

CE AUTHORS

Deborah J. Moonan, RN, BSN, Director, Continuing Education, has disclosed that she has no relevant financial relationships.

Ann Gianola, MA, Manager, Continuing Education Accreditation & Program Operations, has disclosed that she has no relevant financial relationships.

Kristina M. Gregory, RN, MSN, OCN, Vice President, Clinical Information Operations, has disclosed that she has no relevant financial relationships.

Rashmi Kumar, PhD, Senior Manager, Clinical Content, has disclosed that she has no relevant financial relationships.

Hema Sundar, PhD, Oncology Scientist/Senior Medical Writer, has disclosed that she has no relevant financial relationships.

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Correspondence: Rebecca K.S. Wong, MBChB, MSc, FRCPC, Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. E-mail: Rebecca.wong@rmp.uhn.on.ca

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