A Research Guide for
Esophageal Cancer

FDA-APPROVED MAY 2021 The CheckMate 577 trial (NCT02743494) established nivolumab as the standard adjuvant therapy after neoadjuvant chemoradiation and esophagectomy for patients with residual disease. First adjuvant immunotherapy approval in esophageal cancer.

• Median disease-free survival: 22.4 months (nivolumab) vs. 11.0 months (placebo) — HR 0.69, a 31% reduction in risk of recurrence or death
• Benefit consistent across both adenocarcinoma and squamous cell carcinoma
• Dosing: Nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks for up to 1 year
• Who qualifies: Must have completed neoadjuvant chemoradiation (not chemotherapy alone) + surgery + confirmed residual viable tumor in the specimen

FDA-APPROVED MARCH 2021 KEYNOTE-590 (NCT03189719): pembrolizumab + cisplatin + 5-FU as first-line standard for advanced esophageal cancer. First immunotherapy approval in first-line esophageal cancer in the US.

• ESCC with PD-L1 CPS ≥10: Median OS 13.9 months vs. 8.8 months (HR 0.57)
• All patients: Median OS 12.4 vs. 9.8 months

FDA-APPROVED APRIL 2022 CheckMate 648 (NCT03143153) established two nivolumab-based first-line options for advanced esophageal SCC:

• Nivolumab + cisplatin + 5-FU: Median OS 15.4 vs. 9.1 months (HR 0.54) in PD-L1 CPS ≥1 patients
• Nivolumab + ipilimumab (chemotherapy-free): Median OS 13.7 vs. 9.1 months (HR 0.64) in PD-L1 CPS ≥1. Particularly valuable for patients who cannot tolerate platinum chemotherapy.

FDA-APPROVED MAY 2021 / FULL APPROVAL 2024 KEYNOTE-811 (NCT03615326): pembrolizumab + trastuzumab + chemotherapy is now the preferred first-line regimen for HER2-positive advanced gastric, GEJ, and esophageal adenocarcinoma. Replaces the prior trastuzumab + chemotherapy-alone standard (ToGA regimen).

• ORR: 74% (pembrolizumab arm) vs. 52% (trastuzumab + chemotherapy alone)
• Median OS (final analysis 2024): 20.0 vs. 16.8 months (HR 0.84)

FDA-APPROVED JANUARY 2021 DESTINY-Gastric01 (NCT03329690): T-DXd vs. physician’s choice chemotherapy in previously trastuzumab-treated HER2+ gastric/GEJ cancer:

• ORR: 51.3% vs. 14.3%
• Median OS: 12.5 vs. 8.4 months (HR 0.59)

FDA-APPROVED OCTOBER 2024 Zolbetuximab (VYLOY; Astellas Pharma): first approval specifically targeting the Claudin 18.2 protein. For HER2-negative gastric or GEJ adenocarcinoma that is CLDN18.2-positive, in combination with mFOLFOX6 or CAPOX.

• SPOTLIGHT (NCT03504397): Median OS 18.2 vs. 15.5 months; PFS 10.6 vs. 8.7 months
• GLOW (NCT03653507): Median OS 14.4 vs. 12.2 months; PFS 8.2 vs. 6.8 months
• EMA approval also granted in 2024; approved in Japan and EU simultaneously

SCC arises from the flat squamous cells that line the upper two-thirds of the esophagus. It is the dominant type worldwide, particularly in East Asia, East Africa, and Iran. In the United States, it represents about 30% of esophageal cancers and is more common in the upper and middle esophagus. Risk factors are tobacco and alcohol. It is not associated with Barrett’s esophagus.

Treatment: SCC is exquisitely sensitive to radiation, which is why definitive chemoradiation (chemotherapy plus radiation without surgery) is an established option for some patients. The CROSS trial included both SCC and adenocarcinoma patients, and SCC patients had a striking pathologic complete response rate of 49% to neoadjuvant chemoradiation, compared to 23% for adenocarcinoma. Immunotherapy with nivolumab (FDA-approved in first-line metastatic SCC via CheckMate 648) and pembrolizumab (via KEYNOTE-590) has become part of first-line treatment.

Adenocarcinoma arises from glandular cells, almost always in the lower third of the esophagus or at the gastroesophageal junction (GEJ). It is the dominant type in the United States, United Kingdom, and Australia, and its incidence has risen dramatically since the 1970s, parallel to rising rates of obesity and GERD. The typical patient is an overweight middle-aged man with chronic heartburn.

GEJ tumors (Siewert type I and II) are biologically and anatomically close to lower esophageal adenocarcinoma and are treated with the same protocols. Siewert type III tumors (true gastric cardia cancers) are treated as gastric cancer.

HER2 testing is critically important for adenocarcinoma. Approximately 15-20% of GEJ adenocarcinomas overexpress HER2, and these tumors respond to trastuzumab-containing regimens. FLOT4 (docetaxel, oxaliplatin, leucovorin, and fluorouracil) perioperative chemotherapy is the standard perioperative regimen for resectable gastroesophageal adenocarcinoma in fit patients.

Small cell carcinoma of the esophagus: Rare (less than 1% of esophageal tumors). Behaves like small cell lung cancer and is treated similarly with chemotherapy (cisplatin/etoposide). Prognosis is generally poor.

Gastrointestinal stromal tumor (GIST) of the esophagus: Extremely rare. Treated with imatinib (Gleevec) if the tumor carries a KIT or PDGFRA mutation, consistent with gastric GIST protocols.

Primary esophageal melanoma: Extremely rare. Requires specialized management.

Leiomyoma: A benign smooth muscle tumor of the esophagus, not a cancer. Commonly found incidentally. Does not require treatment unless symptomatic.

• Upper endoscopy (EGD) with biopsy: The starting point. Allows direct visualization of the tumor, determination of its location and extent, and tissue biopsy for diagnosis and biomarker testing.
• Endoscopic ultrasound (EUS): The most accurate tool for determining tumor depth (T stage) and regional lymph node involvement. A specialized endoscope with ultrasound capability images the layers of the esophageal wall and surrounding nodes. Fine-needle aspiration of suspicious lymph nodes can be performed during the same procedure.
• CT scan of the chest, abdomen, and pelvis: Essential for detecting distant metastases, particularly to the liver, lungs, and distant lymph nodes.
• PET scan (FDG-PET/CT): Standard in the workup of esophageal cancer at most centers. PET is more sensitive than CT for detecting occult metastases and can upstage approximately 10-20% of patients thought to have locoregional disease. It also provides a metabolic baseline for assessing treatment response.
• Bronchoscopy: Required for tumors of the upper and middle esophagus to rule out invasion of the tracheobronchial tree, which would make surgery impossible.
• Diagnostic laparoscopy: Sometimes performed for GEJ adenocarcinoma to rule out peritoneal metastases not visible on imaging. Peritoneal metastases are not detectable by CT or PET and change the treatment plan from curative intent to palliative.

T (Tumor depth into esophageal wall):

• Tis: High-grade dysplasia (pre-invasive). Treated endoscopically.
• T1a: Tumor invades the lamina propria or muscularis mucosae. Endoscopic resection may be curative.
• T1b: Tumor invades the submucosa. Surgery usually required.
• T2: Tumor invades the muscularis propria.
• T3: Tumor invades the adventitia (outer layer). Most stage III tumors are T3.
• T4a: Resectable tumor invading adjacent structures (pleura, pericardium, azygos vein, diaphragm, peritoneum).
• T4b: Unresectable tumor invading aorta, vertebral body, trachea, or other critical structures.

N (Lymph node involvement):

• N0: No regional lymph node metastasis.
• N1: 1-2 regional lymph nodes involved.
• N2: 3-6 regional lymph nodes involved.
• N3: 7 or more regional lymph nodes involved.

M (Distant metastasis): M0 (none) or M1 (present). The most common sites of metastasis are liver, lungs, bone, and distant lymph nodes (celiac, supraclavicular).

Overall stage groupings (AJCC 8th edition, squamous cell):

• Stage 0: Tis, N0, M0
• Stage I: T1, N0-1, M0
• Stage II: T2-3, N0-1, M0
• Stage III: T2-4a, N2-3, M0 or T3-4a, N1-2, M0
• Stage IVA: T4b any N M0, or any T N3 M0
• Stage IVB: Any T, any N, M1

Note: Adenocarcinoma staging uses the same TNM descriptors but slightly different groupings. The specific grade (G1-G3) also enters staging for adenocarcinoma. Ask your oncologist which staging system applies to your tumor type.

• HER2 (ERBB2) testing: Approximately 15-20% of esophageal and GEJ adenocarcinomas overexpress HER2 protein or amplify the HER2 gene. HER2-positive status (IHC 3+ or IHC 2+ with FISH amplification) makes patients eligible for trastuzumab plus chemotherapy in first-line metastatic treatment. HER2 testing is less relevant for squamous cell carcinoma but should still be performed for adenocarcinoma. HER2 status can change between primary tumor and metastases, so re-testing metastatic tissue is appropriate if HER2 status was negative at diagnosis.
• PD-L1 expression (CPS score): The combined positive score (CPS) measures PD-L1 expression in tumor cells plus immune cells. A CPS of 10 or higher identifies patients most likely to benefit from pembrolizumab. A CPS of 1 or higher qualifies patients for nivolumab under FDA-approved labeling. This test is mandatory before starting first-line metastatic therapy and determines which immunotherapy regimen is appropriate.
• Mismatch repair / MSI testing (dMMR/MSI-H): A small proportion (3-5%) of esophageal cancers are mismatch repair deficient or microsatellite instability-high. These tumors respond exceptionally well to checkpoint inhibitors. Pembrolizumab is FDA-approved for MSI-H solid tumors regardless of histology.
• NTRK fusions: Rare but important. Found in less than 1% of esophageal cancers. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) produce dramatic responses in NTRK fusion-positive tumors regardless of cancer type.
• Comprehensive genomic profiling (NGS panel): For patients with advanced esophageal cancer, a comprehensive next-generation sequencing panel can identify additional actionable alterations beyond HER2 and NTRK, including FGFR amplifications, PIK3CA mutations, and others that may be targetable in clinical trials. Ask about FoundationOne CDx or a comparable hospital-based NGS panel.

• Have all four essential biomarkers been ordered: HER2, PD-L1 CPS, MMR/MSI, and NTRK?
• Has a comprehensive NGS panel been ordered for my advanced disease?
• If my HER2 status was negative at diagnosis, should we re-test the metastatic site?
• What is my PD-L1 CPS score exactly? Does it cross the 1 or 10 thresholds that determine immunotherapy eligibility?
• Are there any clinical trials available based on my tumor's molecular profile?

1. Confirm the diagnosis and request the pathology report. Get a copy of your biopsy report. Confirm the tumor type (squamous cell carcinoma vs. adenocarcinoma), grade, and what biomarkers have been tested.
2. Order all biomarkers immediately. If HER2, PD-L1 CPS, MMR/MSI, and NTRK have not been ordered, ask for them now. Results take 1-2 weeks and must not delay treatment planning.
3. Complete the staging workup. Confirm that EUS, CT chest/abdomen/pelvis, and PET/CT have been ordered or are scheduled. For upper/middle esophagus tumors, confirm bronchoscopy is planned.
4. Request a multidisciplinary tumor board review. Your case should be discussed by a team that includes at minimum: a thoracic/GI surgeon, medical oncologist, radiation oncologist, gastroenterologist, radiologist, pathologist, and dietitian. This is the standard of care at high-volume centers.
5. See a dietitian immediately. Do not wait for treatment to start. Begin nutrition assessment and planning now. Many patients need nutritional support established before treatment begins.
6. Consider a second opinion. A second opinion from a high-volume esophageal cancer center is not an insult to your current doctors — it is appropriate due diligence for a serious diagnosis. Most oncologists support this, and it rarely causes meaningful delays.
7. Ask about clinical trials. Even before deciding on a treatment plan, ask whether there are clinical trials for which you might be eligible. Trial eligibility is stage- and treatment-history-dependent, and some trials are only open to patients who have not yet received certain treatments.
8. Address practical matters early. Contact your insurance company to understand pre-authorization requirements. Ask the cancer center about a financial counselor or patient navigator. Arrange support for driving, household tasks, and childcare if needed.

Hospital and surgeon volume is one of the strongest predictors of esophagectomy outcomes. Large population studies consistently show that esophagectomy at high-volume centers (typically defined as 20+ esophagectomies per year) is associated with lower in-hospital mortality, fewer complications, shorter hospital stays, and better long-term survival compared to low-volume centers.

What to look for in a center:

• NCI-designated cancer center or equivalent high-volume program
• Multidisciplinary esophageal cancer clinic (one appointment with surgeon, medical oncologist, radiation oncologist)
• High esophagectomy volume (ask how many the surgeon does per year)
• Minimally invasive esophagectomy expertise
• Dedicated esophageal cancer dietitian and speech-language pathologist
• Active clinical trials in esophageal cancer
• Availability of endoscopic therapies (ESD, EMR) for early-stage disease

Patients in Utah and the Mountain West: Huntsman Cancer Institute at the University of Utah (801-585-0255; 2000 Circle of Hope Drive, Salt Lake City, UT 84112) is the regional comprehensive cancer center and the appropriate starting point for high-volume esophageal cancer care in the region.

Dietary modification: A registered dietitian with oncology experience should see you immediately. High-calorie, high-protein soft foods and liquids can maintain intake in early dysphagia.

Esophageal stenting: A plastic or metal stent can be placed endoscopically to hold open a narrowed esophagus, allowing eating to resume. Stenting provides rapid symptom relief but has limitations: stents can migrate, cause reflux, or interfere with radiation if placed in certain locations. The decision to stent before chemoradiation requires careful multidisciplinary discussion.

Feeding tube (jejunostomy or nasogastric): For patients who cannot maintain adequate nutrition orally, a feeding tube is often placed before or early in treatment. A jejunostomy tube (placed surgically or laparoscopically through the abdominal wall directly into the small intestine) is preferred for patients undergoing esophagectomy. A nasogastric tube is an alternative for short-term use. Enteral feeding through a tube is nutritionally complete and allows full-calorie delivery even when the mouth and esophagus are bypassed.

Nutritional targets during treatment: The general targets during active cancer treatment are 25-35 kcal/kg/day of calories and 1.2-1.5 g/kg/day of protein. A dietitian will calculate your specific needs based on current weight, activity level, and treatment phase.

A speech-language pathologist (SLP) specializing in swallowing disorders (dysphagia) should be part of your team, particularly if you have upper esophageal or cervical esophageal tumors, or if you will receive radiation to the neck or chest. Radiation can cause fibrosis of the swallowing muscles (radiation-induced dysphagia), which is a long-term complication that worsens over time without proactive swallowing exercises.

Swallowing exercises before and during radiation: Research supports the use of prophylactic swallowing exercises during radiation to maintain muscle function. Ask your radiation oncologist about referring to an SLP for pre-treatment baseline evaluation and exercise instruction.

After esophagectomy: Swallowing changes significantly after the esophagus is removed and a stomach pull-up or colon interposition reconstructs the conduit. A dietitian and SLP will guide the graduated return to eating, which begins with clear liquids and progresses over weeks to a modified diet.

• Can I see a dietitian who specializes in esophageal cancer this week?
• Do I need a feeding tube before treatment starts? What type, and who places it?
• Should a stent be placed to help me eat while I get staging tests done?
• How much weight loss is acceptable, and at what point do we need to intervene?
• Is there an SLP on your team who specializes in swallowing rehabilitation?
• Should I start swallowing exercises before radiation begins?
• What will eating look like after surgery? What foods will I need to avoid?

Ivor Lewis esophagectomy: The most common approach for mid- and lower esophageal and GEJ tumors. Involves abdominal incision to mobilize the stomach, then a right thoracic incision to remove the esophagus. The stomach is fashioned into a tube (gastric conduit) and pulled up into the chest to restore continuity. The anastomosis (connection) is in the chest.

McKeown (three-hole) esophagectomy: Used for upper esophageal tumors or when the cervical esophagus must be removed. Three incisions: abdomen, right chest, and neck. The anastomosis is in the neck.

Transhiatal esophagectomy: Performed through abdominal and neck incisions without a thoracic incision. Less invasive in terms of chest access but may provide less thorough lymph node dissection for some tumor locations.

Minimally invasive esophagectomy (MIE): Increasingly performed at expert centers using laparoscopy and thoracoscopy (or robotic-assisted). MIE has equivalent oncologic outcomes to open surgery and is associated with fewer pulmonary complications and shorter hospital stays. Robotic-assisted esophagectomy (RAMIE) is gaining adoption at major centers. Ask whether minimally invasive surgery is available and appropriate for your case.

Colon interposition: When the stomach cannot be used as a conduit (due to previous surgery, tumor involvement, or inadequate blood supply), a segment of colon is used to bridge the gap. Less common but an important option when the stomach is unavailable.

Surgery is appropriate for patients with stage I-IVA resectable disease who are medically fit. The key factors:

• Tumor resectability: T4b tumors invading the aorta, vertebral body, or trachea are generally unresectable. Tumor board review with a thoracic surgeon is needed to make this determination.
• Absence of distant metastases: Patients with M1 disease (stage IVB) are generally not candidates for curative surgery. Rare exceptions exist for highly selected patients with limited, resectable metastases.
• Cardiopulmonary fitness: Esophagectomy requires adequate heart and lung function. Formal cardiopulmonary exercise testing (CPET) is used at some centers to assess fitness. Spirometry and cardiac evaluation are standard preoperative assessments.
• Nutritional status: Severe malnutrition increases surgical risk. Nutritional optimization before surgery (prehabilitation) can reduce complications.
• Performance status: Patients must be capable of tolerating a major operation. ECOG performance status 0-1 is typical for surgical candidates.

For patients who are medically unfit for surgery or who decline surgery, definitive chemoradiation is an established alternative with curative intent for squamous cell carcinoma. For adenocarcinoma, surgery remains the preferred curative approach, and definitive chemoradiation is used when surgery is not feasible.

Esophagectomy is associated with significant complications even at expert centers. Understanding these helps patients prepare and recognize early warning signs.

Common complications:

• Anastomotic leak: The connection (anastomosis) between the stomach tube and the remaining esophagus can leak in up to 10-15% of cases. May require drainage, repeat endoscopy, or additional surgery. Cervical anastomoses are more likely to leak but less dangerous when they do.
• Pulmonary complications: Pneumonia, atelectasis, and respiratory failure are the most common serious complications. Respiratory therapy, early mobilization, and incentive spirometry are standard prevention.
• Conduit ischemia: If blood supply to the stomach conduit is inadequate, the conduit can develop ischemia or necrosis. Rare but serious.
• Recurrent laryngeal nerve injury: Hoarseness resulting from injury to the nerve controlling vocal cord movement. More common with cervical anastomosis. May resolve over weeks to months.
• Chylothorax: Leakage of lymphatic fluid (chyle) into the chest cavity due to injury to the thoracic duct. Managed with dietary fat restriction, chest drainage, and sometimes surgery or radiologic embolization.
• Dumping syndrome: Rapid gastric emptying after the pylorus is disrupted or bypassed causes symptoms of nausea, sweating, and diarrhea after eating. Managed with dietary modifications (small, frequent, low-carbohydrate, low-sugar meals).
• Reflux: Near-universal after esophagectomy because the lower esophageal sphincter is removed. Head-of-bed elevation, small meals, and proton pump inhibitors are standard management.

Hospital stay and recovery: Hospital stay is typically 7-14 days at expert centers. Full recovery takes 6-12 weeks. Most patients require ongoing dietary adjustments for months to years after surgery. Working with a dietitian long-term is important.

• How many esophagectomies do you perform per year? How many does this hospital do per year?
• Is a minimally invasive or robotic approach appropriate for my case?
• What type of esophagectomy is planned: Ivor Lewis, McKeown, or transhiatal?
• Will chemotherapy and radiation be given before surgery (neoadjuvant)?
• What is my risk of the most common complications?
• How long is the hospital stay, and what does recovery look like?
• Will I need a feeding tube before surgery? How long will it remain?
• What dietary changes will be permanent after surgery?

The CROSS trial (NCT01250951) established neoadjuvant chemoradiation followed by surgery as the standard of care for resectable esophageal cancer in most of the world. Published in the New England Journal of Medicine in 2012 and updated with long-term follow-up, the trial compared surgery alone versus weekly carboplatin plus paclitaxel chemotherapy given concurrently with 41.4 Gy of radiation, followed by surgery.

Results: Median overall survival was 49 months with neoadjuvant chemoradiation versus 24 months with surgery alone. Pathologic complete response (no residual viable tumor in the surgical specimen) was achieved in 29% of patients overall, including 49% of squamous cell carcinoma patients and 23% of adenocarcinoma patients. Neoadjuvant chemoradiation did not significantly increase surgical morbidity or mortality.

Current use: The CROSS regimen (carboplatin AUC 2 + paclitaxel 50 mg/m2 weekly x 5 weeks + 41.4 Gy in 23 fractions) is the standard neoadjuvant chemoradiation approach for resectable esophageal and GEJ cancer in the United States and most of Europe. It is followed by surgery 4-8 weeks after completion of radiation.

For patients who are medically unfit for surgery, who decline surgery, or who have squamous cell carcinoma of the upper esophagus (where surgery is particularly complex and radical), definitive chemoradiation with curative intent is an established approach.

Standard regimens: Cisplatin plus fluorouracil (5-FU) combined with radiation to 50-50.4 Gy has historically been the standard, based on the landmark RTOG 85-01 trial. Carboplatin plus paclitaxel (the CROSS regimen doses) with higher radiation doses (50.4 Gy) is increasingly used.

Outcomes: Long-term cure rates with definitive chemoradiation are lower than with combined-modality therapy (surgery plus chemoradiation) for most esophageal cancers, but some patients achieve durable remission, particularly those with clinical complete response after treatment. SCC has higher complete response rates than adenocarcinoma.

Salvage surgery: Patients who have disease recurrence or persistence after definitive chemoradiation may be candidates for salvage esophagectomy at expert centers. Salvage surgery carries higher complication rates than upfront surgery but can be curative in selected patients.

Active surveillance after complete response: Some centers now offer active surveillance (watch-and-wait) to patients who achieve clinical complete response after chemoradiation, reserving surgery for recurrence. This approach is more established for SCC in Asia and Europe but remains investigational in the United States.

During treatment (acute):

• Esophagitis: Radiation inflames the esophageal lining, worsening dysphagia and causing pain. Typically begins 2-3 weeks into treatment and peaks at 4-5 weeks. Pain medication, viscous lidocaine, and nutritional support (often through a feeding tube) are standard management.
• Fatigue: Very common, often cumulative, typically resolves 4-8 weeks after completion.
• Skin reaction: Redness and irritation of the chest skin in the radiation field. Managed with moisturizing creams and avoiding friction.
• Nausea: From radiation to the stomach/GEJ region. Antiemetics are prescribed prophylactically.

Long-term (late) effects:

• Radiation-induced esophageal stricture: Scarring of the esophagus can narrow it and cause recurring dysphagia months to years after treatment. Managed with endoscopic dilation.
• Radiation pneumonitis/fibrosis: Inflammation and scarring of lung tissue in the radiation field. Can cause shortness of breath and cough. Modern radiation techniques (IMRT, proton therapy) minimize dose to uninvolved lung.
• Cardiac effects: Radiation to the chest can affect the heart. Long-term cardiac monitoring is appropriate.
• Swallowing dysfunction: Radiation-induced fibrosis of swallowing muscles is a known late effect. Prophylactic swallowing exercises during radiation reduce this risk.

The FLOT4 trial (NCT01216644), published in Lancet 2019, compared FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, fluorouracil 2600 mg/m2 as 24-hour infusion, every 2 weeks x 4 cycles before and 4 cycles after surgery) against ECF/ECX (epirubicin, cisplatin, fluorouracil/capecitabine) for resectable esophagogastric adenocarcinoma.

Results: Median overall survival was 50 months with FLOT versus 35 months with ECF/ECX. Pathologic complete response rate was 16% versus 6%. FLOT became the standard of care for perioperative chemotherapy of resectable gastric and GEJ adenocarcinoma in Europe and is widely used in the United States.

FLOT vs. CROSS: No head-to-head trial directly compares CROSS (neoadjuvant chemoradiation) to FLOT (perioperative chemotherapy) for GEJ adenocarcinoma. In the United States, both are NCCN-recommended. CROSS is often preferred for mid- and upper-esophageal tumors; FLOT is frequently preferred for GEJ and gastric cancers. Institutional expertise influences the choice. The ESOPEC trial (Germany) compared FLOT vs. CROSS for esophageal adenocarcinoma; results were presented at ASCO 2023 showing FLOT superior in 3-year overall survival (57% vs 51%). Ask your team which approach is preferred at your center and why.

Multiple clinical trials are investigating whether adding a checkpoint inhibitor to perioperative FLOT or CROSS improves outcomes for resectable esophageal cancer. The KEYNOTE-585 trial (NCT03221426) tested pembrolizumab added to platinum-fluoropyrimidine chemotherapy in the perioperative setting for gastric/GEJ cancer. The MATTERHORN trial (NCT04592913) is evaluating durvalumab plus FLOT. Results from these trials are informing guidelines as they mature.

Currently, adding immunotherapy to neoadjuvant chemoradiation or perioperative chemotherapy for resectable esophageal cancer is not standard outside of a clinical trial. This is an active area of investigation, and asking about available trials at the time of staging is appropriate.

The CheckMate 577 trial (NCT02743494) enrolled patients with stage II-III esophageal or GEJ cancer who had received neoadjuvant chemoradiation (CROSS-type) followed by esophagectomy but had residual pathologic disease (i.e., the pathology report showed tumor remaining in the surgical specimen — they did not achieve a pathologic complete response). Patients were randomized to nivolumab 240 mg every 2 weeks for the first 16 weeks, then 480 mg every 4 weeks, for up to one year, versus placebo.

Results (published in NEJM 2021): Median disease-free survival was 22.4 months with nivolumab versus 11.0 months with placebo — a doubling. The benefit was seen in both squamous cell carcinoma and adenocarcinoma histologies. PD-L1 status did not predict benefit in this setting.

FDA approval: Nivolumab received FDA approval in May 2021 for adjuvant treatment of completely resected esophageal or GEJ cancer in patients who had neoadjuvant chemoradiation and residual pathologic disease.

Who qualifies: Patients must have had neoadjuvant chemoradiation (not perioperative FLOT alone) and must have had residual disease on the pathology report after surgery. Patients who achieved pathologic complete response were not included in the trial and do not have an approved adjuvant therapy in this setting.

After completion of curative-intent treatment (surgery with or without adjuvant nivolumab), surveillance is essential because esophageal cancer has a high rate of recurrence, particularly in the first 2 years.

Standard surveillance schedule (NCCN-based):

• History, physical exam, and CEA (if adenocarcinoma): every 3-6 months for 1-2 years, then every 6-12 months for years 3-5, then annually.
• CT chest/abdomen/pelvis: every 6-12 months for the first 2 years, then as clinically indicated.
• Upper endoscopy: not required as routine surveillance at the anastomosis for most patients, but should be performed if symptoms of recurrence develop.
• PET scan: as clinically indicated, not routine.

Patients should also maintain regular follow-up with their dietitian for at least 1-2 years after surgery, as nutritional issues often persist or evolve.

Nivolumab plus chemotherapy (CheckMate 648): The CheckMate 648 trial (NCT03143153) enrolled patients with previously untreated advanced/metastatic ESCC. Nivolumab plus cisplatin and fluorouracil (5-FU) improved overall survival versus chemotherapy alone: median OS 15.4 months versus 9.1 months in PD-L1-positive patients (CPS ≥1), and 13.2 months versus 10.7 months in all patients. FDA approved in 2021 for first-line treatment of unresectable advanced, recurrent, or metastatic ESCC regardless of PD-L1 status.

Pembrolizumab plus chemotherapy (KEYNOTE-590): The KEYNOTE-590 trial (NCT03189719) showed pembrolizumab plus cisplatin and 5-FU improved OS versus placebo plus chemotherapy: median OS 12.4 months versus 9.8 months overall, with greater benefit in PD-L1 CPS ≥10 patients (13.9 vs 8.8 months). FDA approved in 2021 for first-line treatment of metastatic or locally advanced ESCC ineligible for surgical resection or definitive chemoradiation.

Nivolumab plus ipilimumab: CheckMate 648 also included a dual immunotherapy arm. Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg improved OS versus chemotherapy in PD-L1-positive patients. This combination is FDA-approved as an alternative first-line option, particularly useful in patients who cannot tolerate chemotherapy.

ATTRACTION-3 (nivolumab monotherapy, second line): Nivolumab monotherapy is FDA-approved as second-line therapy for ESCC after platinum-based chemotherapy, based on ATTRACTION-3 (NCT02569242) showing median OS 10.9 months versus 8.4 months with chemotherapy.

HER2-negative adenocarcinoma:

Pembrolizumab plus chemotherapy is FDA-approved for first-line treatment of HER2-negative gastric or GEJ adenocarcinoma with PD-L1 CPS ≥1, based on KEYNOTE-811 (NCT03615326). The standard chemotherapy backbone is oxaliplatin plus capecitabine (XELOX/CapeOX) or cisplatin plus fluorouracil.

Nivolumab plus chemotherapy (CheckMate 649, NCT02872116) is FDA-approved for first-line treatment of HER2-negative gastric/GEJ adenocarcinoma: median OS 14.4 months versus 11.1 months overall, with greater benefit in CPS ≥5 patients (15.0 vs 10.9 months).

HER2-positive adenocarcinoma:

Trastuzumab plus chemotherapy (cisplatin/fluoropyrimidine) is standard based on the ToGA trial (NCT01041404, published 2010), which showed median OS 13.8 months versus 11.1 months. Trastuzumab is added to standard chemotherapy for HER2 IHC 3+ or IHC 2+/FISH-positive tumors.

Pembrolizumab plus trastuzumab plus chemotherapy is being studied in KEYNOTE-811, with updated results supporting pembrolizumab addition to the HER2-positive regimen. FDA approved pembrolizumab plus trastuzumab plus chemotherapy for HER2-positive gastric/GEJ adenocarcinoma in 2021.

Trastuzumab deruxtecan (T-DXd, Enhertu) is being investigated in HER2-positive esophageal/gastric cancers in later lines of therapy (DESTINY-Gastric01, NCT03329690; DESTINY-Gastric06). It is FDA-approved for certain HER2-positive gastric cancers and is being evaluated for esophageal adenocarcinoma. Ask about eligibility based on your specific HER2 status and prior therapies.

After progression on first-line therapy, options depend on histology, prior therapy, and molecular profile.

• Ramucirumab (Cyramza): An anti-VEGFR2 antibody, FDA-approved as second-line therapy for gastric and GEJ adenocarcinoma (as monotherapy or with paclitaxel), based on the RAINBOW and REGARD trials. Used regardless of PD-L1 status.
• Nivolumab: FDA-approved second-line for ESCC (ATTRACTION-3). Second-line pembrolizumab is FDA-approved for MSI-H/dMMR esophageal cancer.
• Taxane monotherapy: Docetaxel or paclitaxel as single agents are options for patients who have received platinum-based first-line therapy.
• Irinotecan: Active in gastric/GEJ adenocarcinoma as second- or third-line therapy.
• Trifluridine/tipiracil (Lonsurf): FDA-approved for previously treated gastric/GEJ adenocarcinoma based on TAGS trial (NCT02500043). An oral option.

Cancer cells can evade the immune system by activating the PD-1/PD-L1 checkpoint pathway, which tells immune cells (T cells) to stand down. PD-1 is a protein on T cells; PD-L1 is its ligand, expressed on cancer cells and immune cells. When PD-L1 on a cancer cell binds PD-1 on a T cell, the T cell is suppressed. Pembrolizumab and nivolumab block PD-1, releasing the brakes and allowing T cells to attack the tumor. Ipilimumab blocks CTLA-4, a different checkpoint, and works synergistically with PD-1 inhibition.

The PD-L1 CPS score measures how much PD-L1 is expressed in the tumor environment. Higher CPS scores generally predict greater immunotherapy benefit, which is why this test is critical before starting treatment.

Checkpoint inhibitors can cause the immune system to attack normal tissues as well as cancer. These immune-related adverse events (irAEs) can affect almost any organ and can occur at any time during treatment or even months after stopping. They require prompt recognition and treatment.

Common irAEs to report immediately:

• Colitis: Diarrhea (more than 4 stools per day above baseline), blood in stool, severe abdominal pain. Can be life-threatening if untreated. Treatment: corticosteroids, and infliximab for refractory cases.
• Pneumonitis: New or worsening shortness of breath, cough, or chest pain. CT scan confirms. Treatment: corticosteroids, treatment hold or discontinuation.
• Hepatitis: Elevated liver enzymes (usually detected on routine bloodwork). Usually asymptomatic until advanced. Treatment: corticosteroids.
• Endocrinopathies: Thyroid dysfunction (hypothyroidism or hyperthyroidism, most common), adrenal insufficiency, and hypophysitis (pituitary inflammation causing fatigue, headache, hormone deficiencies). Require hormone replacement therapy, which may be lifelong.
• Skin reactions: Rash, itching, and vitiligo are common. Severe Stevens-Johnson syndrome/toxic epidermal necrolysis is rare but dangerous.
• Nephritis: Rising creatinine on routine labs. Usually requires corticosteroids.
• Myocarditis: Rare but potentially fatal. Symptoms include chest pain, shortness of breath, palpitations, and fatigue. Requires immediate evaluation.
• Neurological irAEs: Include encephalitis, myasthenia gravis, and Guillain-Barre syndrome. Rare but serious.

Key rule: Report any new symptom to your oncology team promptly. Do not assume it is unrelated to your cancer treatment. irAEs can mimic common illnesses and can escalate rapidly if not treated. Your team will instruct you on which symptoms require emergency evaluation versus same-day contact versus routine reporting.

Trastuzumab (Herceptin): The first and still the most widely used HER2-directed therapy in esophageal/GEJ cancer. Added to platinum-fluoropyrimidine chemotherapy in the first line for HER2-positive (IHC 3+ or IHC 2+/FISH+) gastric and GEJ adenocarcinoma. Administered intravenously every 3 weeks.

Trastuzumab deruxtecan (T-DXd / Enhertu): An antibody-drug conjugate (ADC) that links trastuzumab to a topoisomerase I inhibitor payload (deruxtecan). FDA-approved for HER2-positive gastric or GEJ adenocarcinoma previously treated with trastuzumab (DESTINY-Gastric01, NCT03329690, showed 12.5 months median OS vs 8.4 months with chemotherapy). Being evaluated for esophageal adenocarcinoma specifically in DESTINY-Gastric06 (NCT04704934). The drug is particularly notable for its activity in HER2-low tumors in breast cancer; whether this extends to esophageal cancer is under investigation.

Margetuximab (Margenza): An Fc-engineered anti-HER2 antibody that may be an alternative to trastuzumab in later lines. FDA-approved for HER2-positive breast cancer; investigated in gastric/GEJ cancer.

Ramucirumab (Cyramza): An antibody that blocks VEGFR2, a receptor that promotes tumor blood vessel growth. FDA-approved for advanced gastric/GEJ adenocarcinoma in the second line as monotherapy (REGARD trial, NCT00917384) or combined with paclitaxel (RAINBOW trial, NCT01170663). The RAINBOW trial showed median OS 9.6 months with ramucirumab plus paclitaxel versus 7.4 months with placebo plus paclitaxel.

Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek): TRK inhibitors are FDA-approved for any solid tumor with an NTRK gene fusion, regardless of cancer type. NTRK fusions are rare in esophageal cancer (less than 1%) but produce dramatic responses when present. Comprehensive genomic profiling (NGS) is required to identify NTRK fusions, as standard sequencing panels may miss them. If your tumor has been NGS-profiled and an NTRK fusion is identified, ask specifically about larotrectinib or entrectinib.

MATTERHORN (NCT04592913) — Durvalumab + FLOT perioperative:
Phase III trial of durvalumab (anti-PD-L1) + FLOT vs. FLOT alone for resectable gastric/GEJ adenocarcinoma. pCR improved from 7% to 19%. OS data maturing; regulatory submission underway. If approved, this will establish the first perioperative immunotherapy standard for resectable EAC/GEJ cancer, adding to the FLOT backbone.

MATTERHORN (NCT04592913) — Durvalumab + FLOT perioperative (esophageal-specific):
Related AstraZeneca study specifically enrolling esophageal adenocarcinoma. Verify enrollment status at ClinicalTrials.gov.

HERIZON-GEA-01 (NCT05152147) — Zanidatamab for HER2+ GEJ:
Zanidatamab is a bispecific antibody targeting two distinct domains of HER2. Phase III trial evaluates zanidatamab + chemotherapy +/− tislelizumab vs. trastuzumab + chemotherapy as first-line treatment for HER2+ gastric/GEJ adenocarcinoma. Verify enrollment at ClinicalTrials.gov.

KEYNOTE-585 (NCT03221426) — Results published; largely negative for OS:
Evaluated perioperative pembrolizumab + chemotherapy vs. chemotherapy alone for gastric/GEJ adenocarcinoma. While pCR rates improved with pembrolizumab, the primary overall survival endpoint was not met. This was an important negative result that informs current perioperative trial design.

Novel ADC combinations and HER2-directed trials:
Multiple trials are exploring T-DXd in combination with pembrolizumab and other agents. Search ClinicalTrials.gov for “trastuzumab deruxtecan esophageal” to see the current portfolio of open studies.

Step 1: Search ClinicalTrials.gov
Go to clinicaltrials.gov. Search “esophageal cancer” or “gastroesophageal junction cancer,” filter by “Recruiting” and your location.

Step 2: Ask at Huntsman Cancer Institute (HCI)
HCI Clinical Trials Office: 801-585-0303 — huntsmancancer.org/clinical-trials
HCI participates in cooperative group trials (SWOG, Alliance, NRG Oncology) and industry-sponsored phase II/III studies.

Step 3: Contact the Esophageal Cancer Action Network (ECAN)
ECAN (ecan.org) — 1-877-326-3226 — Patient navigators specifically trained in esophageal cancer help match patients to open studies.

Step 4: NCI Cancer Information Service
Call 1-800-422-6237 (1-800-4-CANCER). NCI specialists search trials matching your diagnosis and location.

Bring to your trial consultation: your pathology report, staging workup results, list of prior treatments, ECOG performance status, and any comorbidities (autoimmune disease history, prior organ transplant, cardiac history).

• Is there a trial open at HCI or a nearby center that I qualify for?
• Would the control arm of the trial give me access to the current best standard of care?
• Does trial participation affect my ability to get standard treatment afterward if the trial arm doesn’t work?
• How often would I need to come in for trial visits vs. standard treatment?
• Are trial-related travel, parking, or lodging costs covered?
• Does participating in a trial affect my insurance coverage?
• Can I withdraw from a trial if I change my mind?

Lapatinib (Tykerb): The LOGiC trial (NCT00680901) tested lapatinib added to capecitabine plus oxaliplatin in HER2-positive advanced GEJ and gastric cancer. Despite sound biological rationale, the trial found no improvement in overall survival. The FDA did not approve lapatinib for GEJ or esophageal cancer. The likely explanation is that HER2 gene amplification is often heterogeneous in these tumors — present in some tumor cells but not others — allowing HER2-negative clones to survive and drive progression.

Afatinib (Gilotrif): An irreversible pan-HER family inhibitor evaluated in esophageal and GEJ cancers. Modest signals in small studies were not replicated in larger controlled trials. No approved indication in esophageal cancer.

Cetuximab (Erbitux) was evaluated in two important trials. The EXPAND trial (NCT00678535) tested cetuximab added to cisplatin and capecitabine in advanced gastric and GEJ adenocarcinoma — no survival benefit, additional toxicity. RTOG 0436 evaluated cetuximab added to paclitaxel, cisplatin, and radiation for localized esophageal cancer — no improvement in OS or pCR rate. EGFR amplification does not appear to be a reliable predictive biomarker in esophageal cancer unlike in colorectal cancer.

Gefitinib (Iressa) and Erlotinib (Tarceva): EGFR tyrosine kinase inhibitors tested in early-phase esophageal cancer studies. In unselected populations, these agents show no meaningful advantage. Not approved for esophageal cancer.

Bevacizumab (Avastin): The AVAGAST trial (NCT00548548) tested bevacizumab added to cisplatin and capecitabine in advanced gastric and GEJ adenocarcinoma. No improvement in overall survival (median OS 12.1 vs. 10.1 months; HR 0.87; p=0.1002). Bevacizumab is not approved or recommended for esophageal cancer. The failure is thought to reflect high vascular redundancy in upper GI tumors and the modest contribution of VEGF-driven angiogenesis relative to other growth pathways.

KEYNOTE-585 (NCT03221426) tested perioperative pembrolizumab plus chemotherapy (FLOT or cisplatin/5-FU) versus chemotherapy plus placebo in resectable esophageal and GEJ adenocarcinoma. Published in NEJM Evidence in 2023, KEYNOTE-585 failed its primary endpoints — pathological complete response and event-free survival were not significantly improved by the addition of pembrolizumab. This important negative result tells us that timing and sequence of immunotherapy integration matter enormously; adding pembrolizumab to perioperative chemotherapy alone does not replicate the benefits of post-chemoradiation adjuvant nivolumab (CheckMate 577).

Onartuzumab (anti-MET antibody) added to mFOLFOX6 in MET-positive advanced gastric/GEJ cancer (METGastric trial) failed to improve outcomes and was stopped for futility. A trend toward harm was observed in MET-negative patients inadvertently enrolled due to IHC assay limitations.

Rilotumumab (anti-HGF antibody) was stopped after Phase 3 (RILOMET-1 trial) when interim analysis showed higher mortality in the rilotumumab arm. This reinforced the critical importance of robust, validated biomarker selection before Phase 3 trial design.

The pattern across failed esophageal cancer trials is instructive:

• Biomarker-unselected trials reliably fail in this disease. Trials enrolling all-comers regardless of HER2 status, CLDN18.2, PD-L1 CPS, or EGFR status repeatedly produced null results even when subgroup analyses hinted at benefit in molecularly defined populations.
• Tumor heterogeneity undermines single-target strategies. HER2 heterogeneity allows HER2-negative clones to escape anti-HER2 therapy. Modern ADCs like T-DXd deliver cytotoxic payload to bystander cells — specifically designed to address this limitation.
• Timing of immunotherapy matters. KEYNOTE-585’s failure does not invalidate immunotherapy in esophageal cancer — it refines understanding of when and how checkpoint inhibitors should be incorporated.
• Each failed trial contributed to the precision oncology framework now applied: mandatory HER2, PD-L1 CPS, CLDN18.2, and MSI-H testing for every advanced esophageal/GEJ adenocarcinoma at diagnosis.

Esophageal cancer can cause pain from the tumor itself, from treatment (esophagitis during chemoradiation), and from post-surgical recovery. Effective pain management is a patient right and improves function and quality of life. Do not minimize pain to your medical team.

Approaches: Over-the-counter analgesics for mild pain. Prescription opioids for moderate-to-severe pain. Mucositis management protocols during radiation (viscous lidocaine, magic mouthwash). Nerve blocks for specific pain syndromes. Palliative care consultation for complex or refractory pain. Integrative approaches (acupuncture, mindfulness) as complements to medical pain management.

Cancer-related fatigue is the most commonly reported symptom during and after treatment. It is distinct from normal tiredness and does not fully resolve with rest. Key strategies:

• Structured physical activity: Counterintuitive but well-supported by evidence — moderate aerobic exercise reduces cancer-related fatigue more effectively than rest alone. Even short walks when energy is lowest help maintain conditioning.
• Energy conservation: Prioritize essential activities; accept help for non-essential tasks; schedule activities during peak energy times (often morning).
• Treat contributing causes: Anemia, hypothyroidism (an irAE of immunotherapy), depression, poor sleep, and malnutrition all worsen fatigue and are treatable.
• Psychostimulants: Methylphenidate or modafinil may help severe fatigue, particularly in advanced disease. Discuss with your oncologist.

Palliative care is specialized medical care focused on relief from pain, symptoms, and the stress of serious illness. It works alongside curative or life-prolonging treatment, not instead of it. Randomized controlled trials have shown that early palliative care integration improves quality of life, reduces aggressive end-of-life care, and in some studies has been associated with longer survival.

Ask for a palliative care consultation at diagnosis, not just at end of life. Topics addressed include: symptom management, communication about goals of care, advance care planning, caregiver support, and transitions of care.

Depression and anxiety are highly prevalent in esophageal cancer, affecting an estimated 20-40% of patients. They are underdiagnosed and undertreated. Symptoms that are written off as "understandable given the diagnosis" may actually be clinical depression or anxiety disorders that respond well to treatment.

• Oncology social workers: Present at most cancer centers; can coordinate counseling, support groups, practical assistance, and community resources.
• Cancer-specific psychotherapy: Cognitive-behavioral therapy and acceptance and commitment therapy adapted for cancer patients are evidence-based.
• Support groups: Peer support from others with esophageal cancer. The Esophageal Cancer Action Network (ECAN) at ecan.org has peer support connections and a patient navigator program.
• Medications: Antidepressants or anxiolytics when appropriate, prescribed by a psychiatrist experienced with oncology patients.

Structured exercise is beneficial before, during, and after esophageal cancer treatment. Prehabilitation (exercise before surgery) improves cardiopulmonary fitness and reduces surgical complications. During treatment, moderate exercise reduces fatigue, improves mood, maintains muscle mass, and may improve treatment tolerance. After treatment, regular exercise reduces cancer recurrence risk and improves long-term survival in multiple cancer types.

Practical guidance: Aim for 150 minutes of moderate aerobic activity per week when physically able (walking, cycling, swimming). Add resistance training 2-3 days per week to preserve muscle mass, which is often lost during cancer treatment. Start slowly and build gradually. Work with a cancer rehabilitation specialist or physical therapist if fatigue, weight loss, or treatment side effects limit activity. Ask your oncologist or care team to refer you to an oncology rehabilitation program.

Esophageal cancer caregiving carries specific stressors:

• Prolonged treatment duration: Neoadjuvant chemoradiation followed by esophagectomy recovery followed by adjuvant immunotherapy (up to 12 months) means caregiving extends for 18 months or longer without a clear endpoint.
• Nutrition is a constant preoccupation: Caregivers spend extraordinary time and energy on meal preparation, calorie tracking, tube feeding management, and advocating for nutritional support.
• Tube feeding at home: If a jejunostomy (J-tube) or gastrostomy (G-tube) is placed, caregivers must learn to administer formulas, flush tubes, troubleshoot clogs, monitor the tube site, and manage delivery pumps during overnight feeds.
• Post-esophagectomy adjustment: After surgery, six to eight small meals daily are required. The social aspects of eating change permanently.

Warning signs of caregiver burnout: Sleep disruption, emotional numbness or irritability, neglecting personal health appointments, social isolation, persistent sadness or anxiety. Reaching out for support is not weakness — it is essential to your ability to continue providing care.

Daily flushing protocol:

• Flush the tube with 30 mL of plain water every 4 hours during the day (and before and after each tube feeding and each medication) to prevent clogging.
• If the tube is completely clogged and gentle flushing does not restore flow, call your home health nurse or the oncology clinic — do not force the flush.

Medication administration through the tube:

• Never crush enteric-coated, extended-release, or sustained-release medications. Always ask the pharmacist before crushing any medication. Crushing extended-release controlled substances can cause overdose.
• Crush each medication separately, dissolve in 15–30 mL of water, administer, and flush with water between medications.

Tube site care:

• Clean the skin around the tube exit site daily with gentle soap and water. Pat dry thoroughly — moisture promotes skin breakdown and infection.
• Inspect daily for redness, swelling, warmth, or purulent discharge — signs of infection. Also check that the external bumper is not embedded in the skin (buried bumper syndrome), which requires immediate medical attention.

When to call the oncology nurse or go to the ER:

• Complete tube obstruction that does not resolve with gentle flushing
• Tube has been pulled out or is partially dislodged (J-tube dislodgement is a medical emergency)
• Signs of tube site infection (redness, warmth, discharge, fever)
• Fever above 101°F / 38.3°C in a patient receiving chemotherapy or immunotherapy

Keep a symptom diary: Record daily: pain level (0–10), food and fluid intake, weight, bowel function, energy level, and any new symptoms. Bring this log to every appointment. Specific data are far more useful to your oncologist than “about the same as last time.”

Bring a second listener: Research consistently shows patients and caregivers retain only 20–40% of information delivered in a medical visit under stress. Bring a second person, or ask to record the conversation on your phone (tell the team first).

Use the patient portal proactively: MyChart (used at HCI, U of U Health, Intermountain Health) allows caregivers (with patient authorization) to review lab results in real time, message the oncology nurse, and see upcoming appointments.

Ask about after-hours protocols: Know the after-hours number, criteria for going to the ER vs. calling the triage nurse line. For HCI patients: after-hours oncology triage is available through 801-585-0303.

Disease-specific organizations:

• Esophageal Cancer Action Network (ECAN): ecan.org  ·  1-877-326-3226 — Patient navigators, peer mentor program, caregiver resources, virtual support groups, research grant funding.
• Esophageal Cancer Awareness Association (ECAA): ecaware.org — Patient education, support resources, “EC Warriors” peer support network.

General cancer support:

• CancerCare: cancercare.org  ·  1-800-813-4673 — Free professional counseling by licensed oncology social workers; financial assistance grants for treatment-related costs.
• Imerman Angels: imermanangels.org  ·  312-274-5529 — Matches patients and caregivers one-on-one with cancer survivors who have been through a nearly identical situation. Free.
• HCI Social Work Services: 801-585-0303 — Social work services, practical assistance, emotional counseling, connection to financial resources.

Advance care planning is important for all cancer patients — not only those with advanced disease. A POLST (Physician Orders for Life-Sustaining Treatment) form translates your wishes into actionable medical orders. A healthcare directive or living will documents your values and preferences if you cannot speak for yourself.

For patients with stage IV or high-risk stage III esophageal cancer, early conversations with a palliative care team — separate from end-of-life hospice, which is a specific service — can help manage symptoms, set realistic goals of care, and plan ahead, without giving up on treatment.

Research published in JAMA Oncology has shown that early palliative care integration improves quality of life, reduces depression, and in some cancers is associated with longer survival compared to oncology care alone.

• Patient Advocate Foundation: patientadvocate.org — 1-800-532-5274 — Insurance appeals, cost-sharing relief, job retention assistance.
• American Cancer Society: cancer.org — 1-800-227-2345 — Lodging programs (Hope Lodge), transportation assistance, wigs and appearance-related support, emotional support hotline 24/7.
• CancerCare: cancercare.org — 1-800-813-4673 — Free counseling, financial assistance for treatment costs, support groups.
• NeedyMeds: needymeds.org — Database of patient assistance programs for expensive cancer drugs. Many pharmaceutical companies offer free or reduced-cost drugs to uninsured or underinsured patients.
• Manufacturer patient assistance programs: Bristol-Myers Squibb (nivolumab), Merck (pembrolizumab), Genentech/Roche (trastuzumab), and Daiichi Sankyo (T-DXd) all have patient assistance programs for uninsured or underinsured patients. Ask your oncology pharmacist or social worker.
• Social Security Disability Insurance (SSDI): Esophageal cancer may qualify for expedited SSDI processing under the Compassionate Allowances program. ssa.gov — 1-800-772-1213.
• Esophageal Cancer Action Network (ECAN): ecan.org — Disease-specific organization providing patient navigation, support connections, and advocacy. Has a patient navigator program that can help connect to resources.
• Utah resources: Utah Cancer Action Network, 4th Street Clinic (Salt Lake City), and the Utah Department of Health Cancer Program can connect Utah patients to state-specific assistance. Huntsman Cancer Institute has a dedicated financial counselor team.

Advance care planning is the process of making decisions about future medical care in case you become unable to make or communicate decisions yourself. It is not giving up; it is ensuring your wishes are known and honored.

Key documents: Advance directive (living will) specifying treatment preferences; healthcare proxy or durable power of attorney for healthcare naming a trusted person to make decisions if you cannot; POLST (Physician Orders for Life-Sustaining Treatment) form translating your preferences into actionable medical orders for emergency responders.

Discuss advance care planning with your palliative care team, social worker, or primary care physician. Do not leave it until a crisis. Many patients find that having these conversations reduces anxiety and improves the quality of end-of-life care if it is needed.

Table reflects approvals as of June 2026. Approval status and reimbursement vary; verify with national health authority or treating oncologist. NICE recommendations may differ from EMA approval for NHS coverage in England.

Japan has one of the highest esophageal squamous cell carcinoma rates in the world and correspondingly strong expertise in ESCC management. Several agents have received PMDA approval and are part of Japanese clinical practice:

• Nivolumab (Opdivo): Approved by PMDA for ESCC in multiple lines, including first-line combination with chemotherapy.
• The ATTRACTION-3 trial was conducted primarily in Japan, South Korea, and Taiwan, validating nivolumab monotherapy in second-line ESCC.
• Endoscopic submucosal dissection (ESD): Japan pioneered this technique for early esophageal cancer and has extensive expertise. For patients with T1a tumors, Japanese centers offer highly curative ESD with lower morbidity than esophagectomy.

• What type of esophageal cancer do I have: squamous cell carcinoma or adenocarcinoma? What does this mean for my treatment?
• What is my exact TNM stage?
• Have all of these been tested on my tumor: HER2, PD-L1 CPS, MSI/MMR, NTRK? What are the results?
• Has a comprehensive genomic sequencing panel been ordered?
• Has my case been reviewed by a multidisciplinary tumor board?
• Is there a dedicated esophageal cancer team here, or do GI oncologists cover this as part of a broader GI program?
• How many esophagectomies does this center do each year? How many does the surgeon do?
• Should I get a second opinion at a high-volume esophageal cancer center?
• Can I see a dietitian and speech pathologist this week?
• Are there clinical trials available for my stage and tumor type?

• What is the goal of treatment: curative intent, or controlling the disease?
• Which treatment approach is recommended for me: CROSS chemoradiation before surgery, FLOT perioperative chemotherapy, or definitive chemoradiation without surgery? Why this approach over the alternatives?
• What is my expected response rate and the realistic range of outcomes?
• What side effects should I watch for and when do I call you versus the emergency room?
• Do I need a feeding tube? What type, and when should it be placed?
• If I receive immunotherapy, what are the immune-related side effects to report immediately?
• Will I be eligible for adjuvant nivolumab after surgery? This depends on my pathology result.
• How will we know if treatment is working?

• What are my second-line treatment options?
• Should I be re-biopsied to look for new targetable mutations?
• Are there clinical trials I should consider at this point?
• Should I get a consultation at a major esophageal cancer center?
• Should I see palliative care now?
• What does the realistic trajectory of this disease look like from here?
• What are you most worried about? What do you want me to watch for?

Pneumonitis affects roughly 2 to 5 percent of patients on checkpoint inhibitors at a severe level. Watch for a new cough, increasing shortness of breath, or lower-than-normal oxygen level on a pulse oximeter.

• Grade 1 (mild): Pause immunotherapy; arrange repeat CT and pulmonology review.
• Grade 2 (limiting daily activity): Hold immunotherapy; start prednisone 1 mg/kg/day; refer to pulmonologist. Immunotherapy may restart once symptoms resolve to Grade 1.
• Grade 3 or 4 (severe, hospitalization required): Permanently discontinue immunotherapy; IV methylprednisolone 2 mg/kg/day; if no improvement in 48 hours, add mycophenolate or infliximab. Steroid tapers must be slow — minimum 4 to 8 weeks.

Colitis (bowel inflammation): Causes diarrhea, cramps, sometimes blood in stool. Grade 2 (4–6 extra stools/day): hold immunotherapy, start budesonide or systemic prednisone. Grade 3 (>7 extra stools/day, hospitalization needed): IV steroids and often infliximab. Severe colitis can progress to bowel perforation — do not wait to report persistent diarrhea.

Liver inflammation (hepatitis): Liver enzymes (AST, ALT) checked before every infusion. Grade 3 elevation (>5x upper limit of normal): hold immunotherapy, start prednisone 0.5–1 mg/kg/day; hepatology consult may be needed.

Hormone gland problems (endocrinopathies):

• Hypothyroidism (most common): fatigue, weight gain, cold intolerance — treat with lifelong levothyroxine replacement.
• Adrenal insufficiency: severe fatigue, low blood pressure, nausea — treat with hydrocortisone replacement; must not be stopped abruptly.
• Type 1 diabetes: can develop suddenly; symptoms include excessive thirst, frequent urination, unexplained weight loss — insulin therapy must start immediately.
• Hypophysitis (pituitary inflammation): headaches, vision changes, multiple hormone deficiencies — requires hormonal replacement therapy.

Myocarditis: Rare but carries a 25 to 50 percent fatality rate if unrecognized. Report any new chest pain, palpitations, or shortness of breath during immunotherapy immediately. Work-up: troponin, ECG, echocardiogram. Confirmed myocarditis requires urgent cardiology consultation, high-dose methylprednisolone 1 gram/day IV, and permanent immunotherapy discontinuation.

Skin reactions (dermatitis): Grade 1–2 rash (<30% body surface): topical corticosteroids + antihistamines; continue immunotherapy. Grade 3 or blistering reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis): immediate hospitalization, permanent discontinuation, systemic steroids. Never apply topical steroids to blistered or broken skin without guidance.

Nausea and vomiting: Cisplatin-based regimens are among the most nausea-inducing in oncology. Preventive protocols must include all three: a 5-HT3 receptor antagonist (ondansetron or palonosetron), dexamethasone, and an NK1 receptor antagonist (aprepitant or fosaprepitant). Olanzapine 5–10 mg at bedtime is highly effective for breakthrough and delayed nausea. If you cannot keep down fluids for more than 24 hours, call your oncology team or go to an infusion center.

Ramucirumab (Cyramza) — specific warnings: Report any blood in the stool, black tarry stools, vomiting blood, or coughing blood immediately. Take a proton pump inhibitor (such as omeprazole) throughout treatment to protect the stomach lining. Ramucirumab must not be given within 28 days before or after major surgery. Blood pressure must be checked at every visit — goal below 140/90 mmHg.

Trastuzumab deruxtecan (T-DXd/Enhertu) — lung toxicity: Every cycle, report any new respiratory symptoms — shortness of breath, dry cough, fever, or exercise intolerance. Any Grade 2 or higher ILD requires holding T-DXd and starting steroids. Grade 3–4 ILD requires permanent discontinuation.

Acute food impaction: Food completely lodging in the esophagus and unable to pass is a medical emergency. Signs: inability to swallow even saliva, drooling, chest pressure. Go to an emergency room immediately for endoscopic removal. Do not try to force food down with water.

Nutritional crisis: Unintentional weight loss of more than 10 percent of your body weight requires urgent dietitian referral and reassessment of your feeding plan. Options include soft/pureed diet modifications, nasogastric tube for short-term support, gastrostomy or jejunostomy tube for longer-term feeding, and total parenteral nutrition (TPN) through a central line if the gut cannot be used. Malnutrition significantly increases chemotherapy toxicity risk, impairs wound healing, and increases infection risk.

1. What are the first symptoms of immunotherapy lung inflammation I should watch for, and what number should I call at 2 AM?
2. How will we monitor my thyroid and adrenal glands during immunotherapy?
3. If I develop diarrhea, at what point should I call versus go to the emergency room?
4. Do I need a troponin check before each immunotherapy cycle to screen for heart inflammation?
5. What antiemetic medications will I receive before my cisplatin infusion, and what do I take at home afterward?
6. If I am on ramucirumab, should I be on a stomach-protecting medication, and what bleeding signs require me to stop treatment?
7. How will you monitor my lungs if I am receiving T-DXd?
8. What is the plan if my swallowing gets significantly worse during chemoradiation — will I need a feeding tube placed proactively?
9. At what point of weight loss should I call you before my next scheduled appointment?
10. If I need to go to an emergency room, what information should I bring so the ER team knows I am on immunotherapy?
11. How long after finishing immunotherapy do I still need to watch for delayed immune-related side effects?

Esophageal tumors grow inward, progressively narrowing the channel. This causes a characteristic pattern: solid foods become difficult first, then soft foods, then liquids, and in advanced untreated disease, even saliva may not pass. Simultaneously, the tumor releases inflammatory signals that trigger cancer cachexia — a state of accelerated muscle and fat breakdown that cannot be fully reversed simply by eating more. During chemoradiation, mucositis and esophagitis cause acute additional pain and swallowing difficulty. After surgery, the anatomy is permanently altered, requiring lifelong dietary modifications.

Before beginning chemotherapy, radiation, or surgery, every patient should have a formal nutritional assessment using the Malnutrition Universal Screening Tool (MUST) or equivalent. Patients with low muscle mass (sarcopenia) before surgery have significantly higher rates of complications and longer hospital stays — identifying this early allows time for targeted nutritional prehabilitation.

For patients with unresectable or metastatic esophageal cancer, or those awaiting treatment who cannot swallow safely, a self-expanding metal stent (SEMS) can be placed endoscopically to reopen the esophagus. Relief of dysphagia is typically immediate — patients who could previously swallow only liquids can often tolerate soft foods the same day.

Stent complications include migration (the stent moves out of position), tumor ingrowth through the stent mesh (treatable with a second stent), worsening gastroesophageal reflux, and rarely, perforation. Patients with stents should sleep with the head elevated and take a proton pump inhibitor to reduce reflux. Avoid bread, stringy meat, and raw vegetables that can become impacted.

Nasogastric Tube (NGT): Passed through the nose into the stomach. Used for short-term nutritional support. Not suitable for more than a few weeks.

Percutaneous Endoscopic Gastrostomy (PEG): Placed through the abdominal skin into the stomach using endoscopy. For patients who may undergo esophagectomy, endoscopic placement carries a small risk of cancer cell seeding at the PEG site. For surgical candidates, RIG is preferred.

Radiologically Inserted Gastrostomy (RIG): Placed under X-ray guidance without endoscopy, avoiding the tumor. This is the preferred approach for patients who may proceed to esophagectomy, eliminating the cancer seeding risk associated with PEG placement.

Jejunal Feeding Tube (J-tube): After esophagectomy, a small feeding tube is routinely placed through the abdominal wall directly into the small intestine at the time of surgery, allowing early enteral nutrition within 12 to 24 hours. Many patients continue jejunal tube feeding at home for 4 to 8 weeks after surgery.

Total Parenteral Nutrition (TPN): Delivers nutrition through a central venous catheter when the gut cannot be used. TPN is a bridge, not a long-term solution — enteral (gut-based) feeding is always preferred as soon as it is safe, because TPN carries risks including central line infections and liver stress.

The stomach is reshaped into a narrow tube and pulled up into the chest to replace the removed esophagus — a significant anatomical change that permanently alters how you eat.

• Days 1–2: Nutrition through jejunostomy tube only; nothing by mouth.
• Week 1–2: Clear liquids by mouth (after water swallow test confirms no leak).
• Weeks 2–4: Soft and puréed foods — scrambled eggs, yogurt, blended well-cooked vegetables, protein shakes.
• Months 1–3: Full soft diet; chew all food thoroughly to a paste consistency before swallowing.
• Month 3+: Gradual liberalization toward a normal diet, guided by tolerance.

For the rest of your life after esophagectomy: eat six or more small meals per day rather than three large ones; sit upright for at least 30 minutes after eating; do not lie down for at least three hours after your last meal or snack.

Dumping syndrome: When the stomach empties food into the small intestine too rapidly. Early dumping (within 20 minutes of eating): bloating, cramping, nausea, diarrhea. Late dumping (2–3 hours after eating): sweating, shakiness, palpitations from reactive low blood sugar. Minimize by avoiding high-sugar foods, eating small portions slowly, separating liquids from solid meals, and choosing complex carbohydrates and protein-rich foods.

1. Should I be referred to a dietitian now, before I start treatment?
2. Do I need a feeding tube placed before chemoradiation starts — and if so, should it be a PEG or a RIG?
3. If I am a surgical candidate, why is a RIG preferred over a PEG at your institution?
4. Would a palliative esophageal stent improve my quality of life while I am on systemic therapy?
5. What symptoms from my jejunostomy tube should I call about immediately after going home from surgery?
6. How many calories and grams of protein should I be getting each day during treatment?
7. How do I manage dumping syndrome — are there medications that can help if dietary changes are not enough?
8. Will I need to take vitamin B12, iron, or calcium supplements long-term after esophagectomy?
9. Is a speech-language pathologist part of my swallowing rehabilitation after surgery?
10. When will I know if I can stop using my feeding tube and rely entirely on eating by mouth?

Anastomotic stricture: Scar tissue forming at the anastomosis (where the stomach conduit was sewn to the remaining esophagus) occurs in approximately 25 to 40 percent of patients, typically weeks to months after surgery. Treatment: endoscopic dilation (balloon or bougie dilator), repeated as needed. Safe, usually done under mild sedation, reliably improves swallowing.

Gastroesophageal reflux after esophagectomy: Because the lower esophageal sphincter is removed with surgery, reflux of stomach contents into the airway during sleep is a lifelong concern. Aspiration during sleep can cause pneumonia. Sleep with the head of your bed elevated at least 30 degrees (a wedge pillow or bed risers). Take a proton pump inhibitor (PPI) long-term. Avoid eating within three hours of bedtime. Report any new cough or recurrent lung infections — these can be signs of aspiration.

Imaging surveillance: A commonly used framework: CT of the chest, abdomen, and pelvis every 3 to 6 months for the first 2 years, then every 6 to 12 months through year 5, then as clinically indicated. PET-CT is used when recurrence is suspected based on symptoms, not for routine surveillance.

Endoscopic surveillance: Used to assess the anastomosis, dilate any stricture, and look for local tumor recurrence. For patients treated with definitive chemoradiation who did not have surgery, endoscopic surveillance with biopsy is essential to confirm and monitor remission — typically every 3 to 6 months in the first 2 years.

Barrett’s esophagus surveillance: For EAC survivors who retain Barrett’s tissue, ongoing endoscopic surveillance remains important. Recommended intervals: every 3 to 5 years for non-dysplastic Barrett’s; every 6 to 12 months for confirmed low-grade dysplasia; endoscopic ablation therapy (radiofrequency ablation or cryotherapy) for high-grade dysplasia to prevent progression to cancer.

Bone health after long-term PPI use: Long-term PPI therapy interferes with calcium absorption, increasing osteoporosis risk. Ensure adequate vitamin D (at least 1,000–2,000 IU/day) and calcium (1,000–1,200 mg/day from food and supplements combined). A DXA bone density scan should be discussed with your primary care physician, especially if postmenopausal or with other osteoporosis risk factors.

Psychosocial health: Fear of recurrence is the most commonly reported unmet psychosocial need among cancer survivors. Additional burdens specific to esophageal cancer include social isolation from dietary restrictions and changes in body image. Screening for depression and anxiety should be routine at every follow-up visit. Oncology psychologists, licensed clinical social workers, and cancer support groups (including ECAN) provide meaningful help.

Watching for secondary cancers: Patients with squamous cell carcinoma of the esophagus have elevated risk of cancer elsewhere in the upper aerodigestive field (mouth, throat, larynx, lungs) due to field cancerization from shared tobacco and alcohol exposures. Regular dental and head-and-neck examinations are important. If you currently smoke, stopping now substantially reduces your risk of a second primary cancer and improves overall survival.

At the completion of active treatment, ask your oncologist for a written survivorship care plan specifying: which physician is responsible for each aspect of your follow-up (oncologist, surgeon, gastroenterologist, primary care physician); the recommended schedule for imaging and endoscopy; signs and symptoms of recurrence to watch for; a list of all treatments received and their potential late effects; and referrals to supportive services (dietitian, psychologist, physical therapist, tobacco cessation).

Rebuilding physical strength: Cancer treatment — especially surgery and chemotherapy — causes significant loss of muscle mass and cardiovascular fitness. Cancer rehabilitation involves structured aerobic exercise and resistance training, supervised by physical therapists or certified cancer exercise specialists. After esophagectomy, pulmonary rehabilitation may be offered to help restore breathing capacity.

1. What is my exact surveillance schedule for imaging and endoscopy over the next 5 years — and who orders each test?
2. What are the signs of anastomotic stricture, and at what point should I call for an endoscopic dilation?
3. Given that I have Barrett’s esophagus, what is my ongoing surveillance plan?
4. Because I had squamous cell carcinoma, how will you screen me for head-and-neck or lung cancer going forward?
5. Do you have a cancer rehabilitation program, and am I a candidate for supervised exercise training?
6. Should I have a DXA bone density scan given my long-term PPI use?
7. Can you refer me to an oncology psychologist or social worker to help with fear of recurrence?
8. Will you provide me with a written survivorship care plan that I can share with my primary care doctor?
9. Is there anything I can do now — diet, exercise, quitting smoking — that reduces my risk of the cancer coming back?
10. When is the right time to complete an advance care directive or POLST form?

The landmark Temel 2010 study (NEJM) showed that patients with newly diagnosed stage IV lung cancer who received early palliative care alongside standard oncology care reported significantly better quality of life, received less aggressive chemotherapy near the end of life, and lived a median of 2.7 months longer despite receiving less aggressive treatment. This finding has been replicated across multiple cancer types.

For esophageal cancer specifically, the disease burden is substantial from diagnosis: dysphagia causes progressive malnutrition, pain is common, and the emotional weight is enormous. Huntsman Cancer Institute and most major NCI-designated cancer centers now embed palliative care consultation into the standard esophageal cancer care pathway beginning at diagnosis for locally advanced and metastatic disease.

• Esophageal Stenting: Self-expanding metal stents provide immediate relief of dysphagia. Complications include stent migration, tumor ingrowth, and worsening reflux.
• Palliative External Beam Radiation: A short course (typically 30 Gy in 10 fractions, or 20 Gy in 5 fractions) directed at the primary tumor can significantly improve dysphagia within 2–4 weeks. Particularly useful for ESCC, which is highly radiosensitive.
• Gastrostomy and Jejunostomy Tubes: When dysphagia cannot be managed by stenting or radiation, enteral feeding sustains nutrition. The timing requires careful goals-of-care discussion.
• Parenteral Nutrition: TPN is generally not recommended in patients with advanced esophageal cancer no longer receiving active treatment. Studies have not demonstrated survival benefit, and central line complications impose additional burden on patients with limited life expectancy.

Pain management: The WHO analgesic ladder guides escalation. Mild pain: acetaminophen and/or NSAIDs (with GI protection). Moderate pain: low-dose opioids (liquid formulations preferred in patients with dysphagia). Severe pain: strong opioids — transdermal fentanyl patches are particularly valuable for patients who cannot swallow, delivering continuous analgesia without GI absorption. Refractory pain: celiac plexus nerve block (EUS-guided or percutaneous) for upper abdominal pain from GEJ tumors.

Nausea: Nausea is multifactorial in esophageal cancer. Management includes ondansetron or granisetron (5-HT3 antagonists), haloperidol (for opioid-induced and chemical nausea), metoclopramide (prokinetic; contraindicated with complete obstruction), olanzapine 2.5–5 mg at bedtime. For intractable nausea from gastric outlet obstruction, octreotide 100–300 mcg subcutaneously 2–3 times daily reduces GI secretions.

Dyspnea: Low-dose opioids reduce the sensation of air hunger even without improving oxygen saturation — this should not be withheld due to concerns about respiratory depression at palliative doses. Fan therapy (cool airflow toward the face) activates trigeminal nerve fibers and reduces perceived breathlessness.

Tracheoesophageal fistula: A fistula connecting the esophagus and trachea allows aspiration of food and secretions — a medical emergency. Covered esophageal stents can close the fistula from the esophageal side. In comfort-focused patients, crisis medication planning with subcutaneous or IV midazolam and morphine to manage respiratory distress is essential.

Hospice is a specialized program of comfort-focused care for individuals with a life expectancy of six months or less. It can be delivered at home, in a hospice residential facility, in a skilled nursing facility, or in a hospital unit. Hospice is not a place — it is a philosophy and model of care.

What the Medicare Hospice Benefit covers: Nurse visits (from weekly to daily in the final days); 24/7 on-call nurse access; all medications related to the terminal diagnosis; medical equipment (hospital bed, wheelchair, commode, oxygen); chaplain and spiritual care; social work; home health aide; volunteer support; inpatient hospice for symptom crises; respite care for caregivers; bereavement support for family for 13 months after the patient’s death.

Enrollment criteria: Two physicians must certify a prognosis of six months or less. Common indicators in esophageal cancer: ECOG performance status 3–4, progressive disease on all standard therapies, progressive weight loss with failure of nutritional support, recurrent aspiration pneumonia, or patient/family preference for comfort-focused care. Patients who stabilize may be discharged from hospice and can re-enroll if illness later progresses.

• POLST Form (Physician Orders for Life-Sustaining Treatment): A medical order signed by both the patient and physician that specifies CPR preferences, level of medical intervention, and artificial nutrition. Unlike an advance directive, a POLST is an active medical order immediately actionable by EMS and in emergency departments. Post it prominently in the home — typically on the refrigerator. Available from your HCI palliative care team or at polst.org.
• Durable Power of Attorney for Healthcare: Designates a trusted person to make medical decisions on your behalf if you cannot speak for yourself.
• CPR discussion: In-hospital cardiac arrest survival in patients with advanced solid tumors is generally below 15%. This context is essential for an honest conversation about what CPR actually involves and what outcomes are realistic.
• Artificial nutrition discussion: Feeding tubes do not prolong life in patients whose bodies are no longer absorbing nutrients due to the disease itself. Comfort feeding — small amounts of preferred foods for pleasure — can remain meaningful even when tube feeding is no longer appropriate.

• Huntsman Cancer Institute Palliative Care Program: 801-585-0303 | 2000 Circle of Hope Drive, Salt Lake City, UT 84112 — integrated palliative care embedded in HCI oncology clinics; inpatient palliative care consultation available
• University of Utah Palliative Care: 801-581-2121 — inpatient and outpatient consultation
• Intermountain Healthcare Palliative Care: 801-442-2000 — palliative care teams at LDS Hospital, Intermountain Medical Center, and affiliated facilities
• VA Salt Lake City Healthcare System (Wahlen VA): 801-582-1565 — palliative care and hospice for eligible veterans
• ECAN (Esophageal Cancer Action Network): ecan.org — patient and caregiver peer support, advocacy
• CaringInfo (NHPCO): caringinfo.org — advance directive forms for Utah, hospice and palliative care education
• CancerCare: cancercare.org | 1-800-813-4673 — free counseling, support groups, financial assistance
• Crossroads Hospice Utah: 801-736-9444 — community-based hospice services across the Wasatch Front

• Can I receive palliative care at the same time as chemotherapy or immunotherapy?
• Who do I contact when my pain or swallowing becomes worse between appointments?
• Is there a transdermal or liquid formulation of my pain medication since I have difficulty swallowing pills?
• What is the difference between a POLST form and a living will, and do I need both?
• If I enroll in hospice, can I change my mind and return to active cancer treatment?
• What symptoms should prompt me to call hospice for an emergency home visit rather than going to the emergency room?
• Are there palliative options to restore my ability to swallow so I can eat more comfortably?
• What medications will be available at home if I have a breathing crisis or severe pain episode?
• What support is available to my family caregivers — not just to me as the patient?
• Is there a spiritual care counselor at HCI I can speak with even if I am not religious?

Adenocarcinoma

Cancer arising from glandular cells. The most common esophageal cancer type in the US, usually in the lower esophagus near the stomach.

Adjuvant therapy

Treatment given after primary therapy (usually surgery) to reduce the risk of recurrence.

Anastomosis

The surgical connection made between two structures. After esophagectomy, the anastomosis joins the stomach conduit to the remaining esophagus.

Barrett's esophagus

A precancerous change in the esophageal lining caused by chronic acid reflux. Increases risk of adenocarcinoma.

Chemoradiation

Treatment that combines chemotherapy and radiation therapy given at the same time, so each can enhance the other's effect.

CPS (Combined Positive Score)

A measure of PD-L1 protein expression in the tumor environment, used to predict likely benefit from immunotherapy.

CROSS regimen

Neoadjuvant chemoradiation regimen: weekly carboplatin and paclitaxel plus 41.4 Gy radiation, given before esophagectomy.

dMMR / MSI-H

Mismatch repair deficient / microsatellite instability-high. A molecular characteristic that predicts strong response to checkpoint inhibitor immunotherapy.

Dysphagia

Difficulty swallowing. The most common presenting symptom of esophageal cancer.

EGD (Esophagogastroduodenoscopy)

Upper endoscopy. A camera is passed through the mouth to visualize the esophagus, stomach, and duodenum.

EUS (Endoscopic ultrasound)

A specialized endoscope with ultrasound capability used to measure how deeply a tumor has grown into the esophageal wall and whether nearby lymph nodes are involved.

Esophagectomy

Surgical removal of the esophagus, with reconstruction using stomach or colon.

FLOT regimen

Perioperative chemotherapy: docetaxel, oxaliplatin, leucovorin, and fluorouracil given before and after surgery for esophagogastric adenocarcinoma.

GEJ (Gastroesophageal junction)

The point where the esophagus meets the stomach. A common site for adenocarcinoma.

HER2

A protein that promotes cell growth. Overexpressed in 15-20% of esophageal/GEJ adenocarcinomas; targetable with trastuzumab and other drugs.

Ivor Lewis esophagectomy

The most common surgical approach for mid- and lower esophageal cancer, using abdominal and right chest incisions.

irAE (Immune-related adverse event)

A side effect of immunotherapy caused by the immune system attacking normal tissues. Can affect any organ. Requires prompt recognition and treatment.

Minimally invasive esophagectomy (MIE)

Esophagectomy performed using laparoscopic and thoracoscopic (small incision) techniques rather than large open incisions. Reduces pulmonary complications.

Neoadjuvant therapy

Treatment (chemotherapy, radiation, or both) given before surgery to shrink the tumor and improve surgical outcomes.

NGS (Next-generation sequencing)

A comprehensive molecular profiling test that reads multiple cancer genes simultaneously to identify targetable alterations.

Nivolumab (Opdivo)

A PD-1 checkpoint inhibitor approved for adjuvant esophageal cancer (CheckMate 577) and first-line metastatic ESCC (CheckMate 648).

NTRK fusion

A gene rearrangement involving NTRK1, NTRK2, or NTRK3 genes. Rare in esophageal cancer but targetable with larotrectinib or entrectinib regardless of cancer type.

Pathologic complete response (pCR)

No viable tumor remaining in the surgical specimen after neoadjuvant treatment. Associated with improved long-term outcomes.

PD-1 / PD-L1

Proteins involved in an immune "off switch." Cancer cells use PD-L1 to suppress immune attack. Checkpoint inhibitors block this pathway.

Pembrolizumab (Keytruda)

A PD-1 checkpoint inhibitor approved for first-line metastatic esophageal/GEJ cancer (KEYNOTE-590) and for MSI-H solid tumors.

Perioperative chemotherapy

Chemotherapy given both before and after surgery (as opposed to neoadjuvant-only or adjuvant-only approaches).

Squamous cell carcinoma (SCC)

Cancer arising from flat squamous cells lining the upper esophagus. More common in Asia and East Africa; associated with tobacco and alcohol.

T-DXd (trastuzumab deruxtecan, Enhertu)

An antibody-drug conjugate targeting HER2; approved for HER2-positive gastric/GEJ cancer after prior trastuzumab.

TNM staging

The tumor-node-metastasis staging system classifying cancers by depth of invasion (T), lymph node involvement (N), and distant spread (M).

Trastuzumab (Herceptin)

An anti-HER2 antibody used in combination with chemotherapy for HER2-positive gastric and GEJ adenocarcinoma.

• NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. Version 2.2025. National Comprehensive Cancer Network. nccn.org
• van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer (CROSS trial). N Engl J Med. 2012;366(22):2074-84. NCT01250951.
• Al-Batran SE, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial (FLOT4). Lancet. 2019;393(10184):1948-1957. NCT01216644.
• Kelly RJ, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (CheckMate 577). N Engl J Med. 2021;384(13):1191-1203. NCT02743494.
• Doki Y, et al. Nivolumab combination therapy in advanced esophageal squamous-cell carcinoma (CheckMate 648). N Engl J Med. 2022;386(5):449-462. NCT03143153.
• Sun JM, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590). Lancet. 2021;398(10302):759-771. NCT03189719.
• Janjigian YY, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649). Lancet. 2021;398(10294):27-40. NCT02872116.
• Kato K, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma (ATTRACTION-3). Lancet Oncol. 2019;20(11):1506-1517. NCT02569242.
• Bang YJ, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA). Lancet. 2010;376(9742):687-97. NCT01041404.
• Wilke H, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW). Lancet Oncol. 2014;15(11):1224-35. NCT01170663.
• Fuchs CS, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD). Lancet. 2014;383(9911):31-9. NCT00917384.
• Shitara K, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric or gastric oesophageal junction cancer (TAGS). Lancet Oncol. 2018;19(11):1437-1448. NCT02500043.
• Shitara K, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer (DESTINY-Gastric01). N Engl J Med. 2020;382(25):2419-2430. NCT03329690.
• American Cancer Society. Esophagus Cancer. cancer.org. 2025.
• Esophageal Cancer Action Network (ECAN). ecan.org.
• National Cancer Institute. SEER Cancer Statistics. seer.cancer.gov.
• ClinicalTrials.gov. Multiple trials referenced throughout. clinicaltrials.gov.