Esophageal cancer Flashcards by Ned Jones

Esophageal SCC risk factors

smoking, alcohol
radiation
anatomic abnormalities (esophageal webs, achalasia, Zenkers’s)

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Esophageal adenocarcinoma RF’s

Obesity
GERD
Barrett's
High grade dysplasia
Smoking

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Percentage of esophageal cancers that are resectable at diagnosis

50%

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workup of esophageal mass

CBC, CMP
EGD w/ biopsy + *EUS
CT chest, abdomen, pelvis
IF mets not detected with CT –> PET/CT for occult mets (more sensitive)
IF thoracic at or above carina + nonmetastatic –> bronchoscopy (preclude from surgery too)
IF cervical SCC + nonmetastatic –> flexible laryngoscopy (to assess location disease spread + exclude synchronous malignancy)

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histology

adeno (65%)

squamous cell carcinoma (35%)

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distinction in where adenos vs. squamous cell carcinomas occur

Adeno usually in lower third, squamous cell carcinoma in upper 2/3’s

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management of high grade dysplasia

Endoscopic mucosal resection (EMR)
Mucosal ablation
Esophagectomy

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treatment of locally advanced resectable esophageal adenocarcinoma

preoperative or perioperative *concurrent chemoradiation followed by esophagectomy

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management of locally advanced, unresectable disease

Chemoradiation preferred, radiation alone if not chemo candidate

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Life threatening late complication of esophageal cancer

Esophageal-airway fistula (tracheobronchial fistulas) (due to direct tumor invasion into the mainstream bronchus)

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Epidemiologic shift in histologies

adeno becoming more common (as Barrett’s esophagus becomes more prevalent)

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meaning of perioperative chemotherapy

preoperative, intraoperative, and immediately postoperative chemotherapy.

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clinical differences between squamous and adenocarcinoma

Squamous is much more radiosensitive

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Management of locally advanced squamous esophageal cancer

Preoperative chemotherapy and radiation and surgery or definitive chemoradiation (squamous is more radiosensitive)

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What somatic tumor testing do you need for metastatic?

PD-L1
MSI
HER2
NGS for NTRK

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Stage at presentation

Often late
(50-80% of patients present with incurable, locally advanced unresectable or metastatic disease)

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CBC abnormalities associated with esophageal cancer

IDA common due to chronic GI blood loss (bleed a lot)

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Anatomic distinction in where esophageal tumors occur

Cervical vs. thoracic

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Tracheobronchial fistula presentation

Intractable coughing or recurrent pneumonias

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Tracheobronchial fistula treatment

Stent placement

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Most common metastatic sites for esophageal adenocarcinoma

Intraabdominal sites (liver, peritoneum)

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Why you need to use EUS for loco regional staging

Uses a high-frequency US to provide detailed images of esophageal masses and their relationship with the esophageal wall

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When an esophageal mass is unresectable

Invasion of adjacent structures (aorta, vertebral body, airway)

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Use of PET/CT in esophageal cancer

Detect occult metastatic disease in patients who are otherwise believed to be surgical candidates after CT staging

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Role for laparoscopy in staging

- Optional per NCCN - Controversial, usually reserved for patients who have potentially resectable T3 or T4 adenocarcinomas of the EGF OR if suspicion for intraperitoneal metastatic disease

Why is diagnostic laparoscopy sometimes performed

Detect occult intraperitoneal mets in patients with distal esophageal and EGJ adenocarcinoma (CT and PET have low sensitivity for intraperitoneal mets)

How most esophageal adenocarcinoma forms

Chronic GERD leading to metaplasia and then neoplasm

Where esophageal adeno and SCC tends to recur

SCCs -- locoregionally | Distal esophageal adeno --- distant dissemination

Prognosis of adeno vs. SCC

Adeno has a better prognosis (less likely to metastasize through lymphatic spread

Is chemoRT with definitive intent for SCC?

Controversial (some argue surgery isn't needed if complete response to chemoRT but there are higher rates of locally persistent, recurrent disease)

Timing of surgery after chemoRT

5-7 week interval preferred for most patients (arbitrary, no data)

T2N0 disease management

IF adeno --> neoadjuvant concurrent chemoradiotherapy | IF SCC --> resection (assuming <2cm + well differentiated)

Surveillance modalities

Tumor markers if previously elevated CT chest/abdomen (limit the number, particularly in younger individuals given concerns about radiation exposure and risk for second malignancies)

Impact of histology on treatment approach in esophageal cancer

Most studies haven't differentiated but there's an increasing amount of evidence that they differ significantly in terms of pathogenesis, biology and prognosis so that's the future.

tumor markers

CEA | CA 19-9

Initial therapy in general for metastatic SCC esophageal cancer

Chemoimmunotherapy - Pembro + chemo

Initial therapy for metastatic esophageal adenocarcinoma

IF HER2-negative with PD-L1 over expression or deficient mismatch repair --> initial immunotherapy plus chemotherapy

dominant histology of esophageal cancer now

adenocarcinoma

Difference in management between adeno and SCC

adeno -- targeted therapies for HER2 and VEGF | SCC -- immunotherapies (regardless of PDL1 expression)

First line for PDL1 positive advanced esophageal SCC

FOLFOX + nivo

Typical regimen for advanced adeno

IF HER2 --> add trastuzumab IF dMMR or PDL1 positive --> Nivo or pembro + chemo Chemo --> no globally accepted first line regimen, typically FOLFOX, CAPOX

Targeted therapies for metastatic esophageal adenocarcinoma

Her2 -- trastuzumab | VEGF

Ineligibility criteria for trastuzumab from trials

- Valvular heart disease - **Angina requiring antianginals - LVH on echo - clinically significant pericardial effusion - CHF - history of MI - Cardiomegaly on CXR

Tumor testing in esophageal

MSI/MMR PD-L1 HER2 Sequencing

Evidence for ACE/ARBs and beta-blockers in HFpEF?

None have been shown to reduce morbidity or mortality

Indication for bronchoscopy in esophageal cancer workup per NCCN

If tumor is at or above the carina with no evidence of M1 disease (typically mid esophageal tumors are high risk for TEF)

Management of SCC stage I

IF surgical candidate --> Endoscopic resection vs esophagectomy

Response assessment following neoadjuvant chemoradiation in esophageal

FDG-PET/CT (confirm)

management of locally advanced SCC

preoperative CRT --> esophagectomy

RO margin status means

no cancer cells seen microscopically at the primary tumor site

R1 margin status means

Cancer cells present microscopically at tumor site

R2 margin status means

Macroscopic residual tumor at primary cancer site

MSI interpretation

3 categories: MSI-stable (MSS) MSI-low (MSI-L) = 1-29% of markers exhibit instability MSI-high (MSI -H) = 30% or greater of markers exhibit instability

What is a liquid biopsy?

Sampling of non-solid tissue (primarily blood) for cancer diagnosis and monitoring - eg., circulating tumor cells (CTCs)

When liquid biopsies are useful

Patients unable to undergo conventional biopsy

First line regimens for esophageal

Paclitaxel and carboplatin Fluorouracil and oxaliplatin

CROSS regimen + indication

- carboplatin, paclitaxel | - neoadjuvant chemoradiation of esophageal

FLOT regimen is

Docetaxel, oxaliplatin, leucovorin, and 5-FU

T staging that typically makes esophageal unresectable + anatomy

T4b (involving pericardium, pleura, and diaphragm. Do not assume these are unresectable)

what is considered Tis disease?

CIS or high grade dysplasia

Management of Tis disease (high grade dysplasia, CIS)

- endoscopic methods have replaced surgery -- endoscopic resection, RFA, endoscopic resection followed by ablation

Tumors with high risk of occult peritoneal mets

- gastric and GEJ

distinction in management between esophageal thoracic and cervical

- with locally advanced thoracic, neoadjuvant chemoradiation followed by surgery ***with cervical chemoradiation is definitive

significance of tumor above the carina

Need bronchoscopy to rule out a fistula

Regimens for chemoradiation

CROSS - carbo/taxol ***Cisplatin/5-Fu

of lymph nodes that need to be sampled in patient undergoing upfront surgery in esophageal

of lymph nodes that need to be sampled in COLON CANCER

Low grade dysplasia management

Antireflux therapy followed by EGD in 6-12 months (low grade dysplasia is not Tis)

Surveillance following concurrent chemoRT for esophageal

* *Imaging not needed. ASCO recommends against using PET to monitor for recurrence in individuals with any cancer type treated with curative intent. - Just need H&P q3 months. - EGD as clinically indicated

epidemiology of esophageal cancer

- incidence of adeno is rapidly rising, squamous has been stable

T2 disease indicates

muscularis propria invasion

T3 disease indicates

invasion of adventitia

T4 disease indicates

invasion into adjacent structures

CROSS regimen — drugs, duration, drug dosing

weekly carbo (AUC=2) + paclitaxel (50 mg/m2) for 5 weeks and radiation 5 days per week

Actionable Mutation in esophageal

NTRK

terminal to describe lymph node involvement beyond regional distribution

non-regional

Preferred chemo regimen for metastatic esophageal

FOLFOX +/- checkpoint inhibitor depending on PD-L1 status

Terminology for diffusely metastatic disease in oncology

"widely metastatic"

N1 disease

Mets to 1 or 2 regional lymph nodes

T staging indicating

T2 or higher (muscle invasive) + high risk

Management of locally advanced esophageal adeno s/p neoadjuvant chemoRT and surgery with minimal treatment effect

nivo (chemorefractory disease)

protective factor against esophageal adenocarcinoma

H pylori

anatomic point at which distal tumors are considered gastric

below cardia

T1b management

Surgery (unless low risk)

SCC vs adeno in terms of behavior

SCC more aggressive (more likely for lymphatic spread)

Preferred second line for GEJ adeno

Ramucirumab + paclitaxel

Alternative first line regimen for metastatic esophageal

5-fu, cisplatin, and nivo

Adjuvant for esophageal adeno after surgery?

nivo for 1 year

Why TEF is more common in squamous histology

More friable and can necrose chemoradiation

PDL1 threshold for adding nivo in esophageal

CPS greater than 5

Management of early stage, node negative esophageal

mucosal resection or surgery depending on T1a or T1b

What does T1b in esophageal indicate?

Submucosal invasion

Management of HER2 positive stage IV adeno

- add trastuzumab and pembro (addition of pertuzumab did not show benefit)