management issue advanced esophageal cancer speaker: vishal garg moderator: dr. s. sachdeva date: 27...
TRANSCRIPT
MANAGEMENT ISSUE
ADVANCED ESOPHAGEAL CANCER
Speaker: Vishal GargModerator: Dr. S. Sachdeva
Date: 27th Nov, 2009
Issues
Introduction Diagnosis and staging Definitive therapy Palliation of malignant dysphagia Management algorithm
IntroductionSQUAMOUS CELL CARCINOMA
70 % found in upper & middle 1/3rd of esophagus
Most common form of esophageal cancer worldwide
Risk factors Smoking Alcohol Food additives eg
nitrosamines (smoked food)
ADENOCARCINOMA
Distal 1/3rd and at the GE junction
Most common subtype in the US and Western world
Risk factors Barrett’s esophagus GERD Obesity
Diagnosis
Esophagram
Recommended for any patient presenting with dysphagia
Differentiate intramural vs intraluminal lesions
Differentiate intrinsic vs extrinsic compression
DiagnosisEndoscopy
Visualize the lesion Location Biopsy
Recommendation: at least 6 biopsies (standard biopsy forceps)
Lal N, Bhasin DK et al. Gut. 1992
PGI, Chandigarh
Staging2 Classification systems exist:
TNM system T – tumor depth N – Involvement of regional lymph nodes M – Disease to nonregional lymph nodes &
distant sites
WNM system (Ellis system) W –Wall penetration N – number of positive lymph nodes M – Distant disease
TNM staging
Current AJCC 2002 staging
Regional nodes Cervical Esophagus: Scalene,
Internal jugular, Upper and lower cervical, Peri-esophageal, Supraclavicular nodes
Intra-thoracic esophagus: Upper peri-esophageal, Sub carinal, Lower peri-esophageal, mediastinal nodes
Gastro-esophageal junction: Lower esophageal, diaphramatic, para-cardial, left gastric and celiac nodes
Comparison of TNM & WNM
staging systems
EUS CT FDG-PETPooled Sensitivity
Pooled specificity
Pooled Sensitivity
Pooled specificity
Pooled Sensitivity
Pooled specificity
Regional LN metastases
0.80 (0.75–0.84)
0.70 (0.65–0.75)
0.50 (0.41–0.60)
0.83(0.77–0.89)
0.57(0.43–0.70)
0.85 (0.76–0.95)
Celiac lymph node metastases
0.85 (0.72–0.99)
0.96 (0.92–1.00)
Abdominal lymph node metastases
0.42 (0.29–0.54)
0.93 (0.86–1.00)
Distant metastases
0.52 (0.33–0.71)
0.91 (0.86–0.96)
0.71 (0.62–0.79)
0.93 (0.89–0.97)
For detection of regional and celiac lymph node metastases: EUS is most sensitive, whereas CT and FDG-PET are more specific tests.
For distant metastases, FDG-PET may have a higher sensitivity than CT.
Difficult case Old male, chronic smoker, presents with
symptoms of dysphagia, weight loss and anorexia
Investigations reveal a stricture of esophagus
Repeated attempts at endoscopic biopsy negative
Strong suspicion of malignancy
Management????
Role of EUS in malignant stricture
Endoscopic ultrasound mini-probes: small, rotating ultrasound probes
Passed through the working channel of a standard endoscope
Only 2 mm to 3 mm in diameter Frequency between 12 Mhz and 20
Mhz
Role of EUS in malignant stricture
Celiac or retroperitoneal lymph nodes were identified in 18 of 42 (43%) patients with malignant strictures
FNA was attempted in 10 patients and confirmed metastatic disease in 7
Gastrointest Endosc 2000;51:
Role of PET/CT Limited role in evaluating the extent
of primary tumor. T1 and T2 do not show significant
FDG uptake Small regional nodes suspicious on CT
are no better visualized on PET/CT Current role is still not defined in the
management of esophageal cancer.
Diagnosis and staging of esophageal cancer
Staging of advanced esophageal cancer
CECT chest + upper abdomen
Consider chemotherapy
Endoscopic ultrasound
Consider chemo/radiation therapy
PET
Consider chemo/radiation therapy
Surgical resection
Evidence of Stage IV disease
No Evidence of Stage IV disease
Evidence of Stage III-IV diseaseNo Evidence of Stage III-IV
disease
Evidence of Stage III-IV disease
No Evidence of Stage
III-IV disease
Management of advanced esophageal cancer
Definitive therapy
Palliation of malignant dysphagia
Definitive therapy
Surgery remains the treatment of choice
Almost 50% patients are unresectable or inoperable at presentation
Types of esophagectomiesTranshiatal
Exposure is provided by an upper midline laparotomy and a left neck incision.
The thoracic esophagus is bluntly dissected, and a cervical anastomosis created; thoracotomy is not required.
Drawbacks: inability to perform a full thoracic lymphadenectomy, and lack of visualization of the midthoracic dissection.
Transthoracic The Ivor Lewis
esophagectomy combines a laparotomy with right thoracotomy, and produces an intrathoracic anastomosis.
This technique permits direct visualization of the thoracic esophagus, and allows the surgeon to perform a limited lymphadenectomy.
However formal dissection of lymph nodes is not performed
Types of esophagectomiesThree field lymphadenectomy: Widely practiced in Japan En bloc resection of esophagus, azygous vein,
thoracic duct, lateral pleural surfaces, part of pericardium
Dissection of cervical, mediastinal and upper abdominal nodes with RPLD performed
Two field lymphadenectomy: En Bloc resection of esophagus, azygous vein,
thoracic duct along with lateral pleural surfaces and part of pericardium and mediastinal nodes and dissection of upper abdominal nodes with RPLD performed
Neoadjuvant /adjuvant therapy
Neo-adjuvant Chemotherapy Neo-adjuvant Radiation Neo-adjuvant Chemo-Radiation Adjuvant Chemotherapy Adjuvant Radiation Adjuvant chemoradiation
Why Neoadjuvant/Adjuvant therapy In most cases esophageal cancer is a
systemic disease at diagnosis. Surgery alone is curative in a small group of
patients. Patterns of recurrence suggest both local
and systemic failure. Disadvantages: Only 50 % of patients
respond to treatment Delay in surgery Main aim of therapy is to downstage the
lesion so as to make it resectable.
Ann Thorac Surg 2007;83:1257– 64
Ann Thorac Surg 2007;83:1257– 64
Ann Thorac Surg 2007;83:1257– 64
Ann Thorac Surg 2007;83:1257– 64
Chemo-RT + surgery
Surgery alone
Ann Thorac Surg 2007;83:1257– 64
Treatment of choice for locally advanced disease
Chemo-radiotherapy followed by surgical resection (Neo-adjuvant chemo-radiotherapy)
Not candidates for surgery
Radiation alone Combination chemoradiation
Chemoradiation Vs Radiation Herskovic et al
Randomize
Radiation64GyN=62
Cis/5 FUx4Radiation
50GyN=61
Median follow up 5 yrs for all ptsMedian Survival 9.3m
5 yr 0%
Median Survival 14.1m5 yr survival 27% P <0.0001
8 yr 22%Locally advanced adeno or squamous esophageal carcinoma.Cisplatin, 75 mg/m2 intravenously, on the first day of weeks 1, 5, 8, and 11. The patients were given a continuous infusion of fluorouracil, 1 g/m2, for the first 4 days of weeks 1, 5, 8, and 11.Radiation was delivered at 30 Gy in 15 fractions over 3 weeks starting on day 1, followed by 20 Gy in 10 fractions over 2 weeks
N Engl J Med. 1992 Jun 11;326(24):1593-8.
Chemoradiation Vs Radiation The trial was stopped after the
results in 121 patients demonstrated a significant advantage for survival in patients who received combination therapy.
The patients who received combined treatment had fewer local (P less than 0.02) and fewer distant (P less than 0.01) recurrences.
No significant relation of histology to survival noted
Chemoradiation Vs Radiation
Currently accepted chemotherapeutic regimen
Targeted therapy for esophageal cancer
Target Drug
EGFR CetuximabGefitinibErlotinib
EGFR/HER LapatinibTrastuzumabPertuzumab
VEGFR SU6668
VEGF Bevacizumab
Targeted therapy for esophageal cancer
GENETIC POLYMORPHISMS AND PROGNOSIS
Palliation of Malignant Dysphagia
Palliative modalities for esophageal carcinoma
Injection therapy Intratumoral injection of absolute alcohol
results in tissue necrosis and sloughing. Cheap, widely available, and relatively
simple to perform. Case series: initial success rate of 80%–
100% in improving dysphagia. Palliative effect is short-term (<1 month)
Injection therapy Alcohol injection is probably best
reserved for short, protuberant, and nonfibrotic tumors that are not amenable to other endoscopic palliative therapies.
Intratumoral injection of cisplatin/epinephrine gel: experimental therapy till date.
Laser therapyNEODYMIUM YTTRIUM ALUMINUM GARNET (Nd:YAG) LASER
Offers an effective way of palliation
Can coagulate up to 6 mm in depth and can obliterate vessels up to 4 mm in diameter
Successful tumor recanalization can be achieved in more than 90% of appropriately selected patients (those with exophytic and not infiltrating tumors that are unassociated with tight strictures)
Laser therapyNEODYMIUM YTTRIUM ALUMINUM GARNET (Nd:YAG) LASER
Treatments are performed every other day and are usually completed in 3–4 sessions (1 week)
Nd:YAG laser therapy needs to be repeated every 4–6 weeks due to tumor regrowth
Symptomatic relief may result for 1 or more months.
Laser therapy
NEODYMIUM YTTRIUM ALUMINUM GARNET (Nd:YAG) LASERDrawbacks
Equipment cost and availability Technical expertise required by the
operator Difficulty in management of long or
tortuous segments
Role of PDT
PDT has role in ablation of barrett’s mucosa
High prohibitive costs and short life expectancy: limit its role in palliation of malignant dysphagia
ARGON PLASMA COAGULATION
Ablative endoscopic technique
Form of monopolar electrocautery
Only one study till date
Need for repeated sessions
No comparison to ND:YAG laser
Stents
SEMS
SEPS
SEMS
SEMS Wallstent
Gianturco-Rösch Z stent
Ultraflex stent
Stents
Two new stent designs:
Polyflex® stent (Boston Scientific)
Niti-S double stent (Taewoong Medical, Seoul, Korea)
SEMS
Dua stent (Z-stent with a windsock-like antireflux valve)
Choice of SEMS Various trials have failed to demonstrate
superiority of one stent over another
Choice for a particular SEMS primarily depends on device availability, familiarity, and personal preference
Stents are ideal for obstructing midesophageal cancers
Esophageal SEMS are indicated for palliation of tracheo-esophageal fistulas.
Proximal esophageal cancer
Traditionally been regarded as too difficult to manage with stents.
Proximal esophageal cancer
Author Year Number of patients
Distance of the stricture from UES
Technical success
Major complications
Type of stent
Dumonceau JM et al.
1999 17(4) NS 100% NR UltraflexWallstent
Verschuur EM et al.
2007 104 4 cms 95% 18% Ultraflex(57%)
Proximal esophageal cancer
Ultraflex stent because of its relatively low radial force and flexible mesh may be the preferred stent
Strictures as near as 2-4 cms from UES have been successfully stented
TRACHEOESOPHAGEAL FISTULA
Dreaded complication 5% of all cases Can lead to aspiration and respiratory
failure Covered SEMS is the treatment of choice
Closure of the fistula can be achieved with a covered stent in 70%–100% of patients
Raijman I, et al. Gastrointest Endosc 1998;48:
SEMS related complications
Immediate technical complication (5%–17%)
Misplacement (0.3%–5%)
Failed expansion (4%–7%)
Failed deployment (1%–3%)
Migration (0.3%–2%).
Delayed technical complications (9%–18%)
Tumor ingrowth/overgrowth (6%–11%)
Stent migration (3%–7%).
SEMS related complications
Immediate patient complications (7%–15%)
Chest pain (6%– 12%) Bleeding (0.2%– 0.6%) Perforation (0.6%–1%) Death (0.5%–1.4%).
Delayed patient complications up to 27%
Reflux symptoms (4%–5%)
Recurrent dysphagia (8%-9%)
Tracheoesophageal fistulas (1%–3%)
Bleeding (0.5%–4%) Perforation (0.5%– 0.8%) Death as a result of
underlying malignancy occurring within 30 days (7%).
Esophageal SEPS
Advantages of SEPSare: easy removability,ease of repositioning, an equal expansive force as SEMS,and half the cost of SEMS in Europe.
Diseases of the Esophagus (2009)
Management of stent related complications
If dysphagia is recurrentafter stent placement
Tumor ingrowth
PDT
APC
ND YAG laser
If dysphagia is recurrentafter stent placement
Is there any role of radiation therapy after stent placement??
Studies done so far have shown conflicting results
Survival benefit has been shown in some studies
Major complications Creation of a tracheal-esophageal fistula Massive hematemesis from stent erosion
into the aorta.
Current role is not defined
Chemotherapy for palliation of malignant dysphagia
Radiotherapy Doses of 30–37.5 gy are used for
palliation A diagnostic bronchoscopy prior to
radiation therapy is recommended Patients with a suspected
tracheoesophageal fistula should not be treated with radiation therapy
Risk for post-radiotherapy esophageal strictures
Takes longer for symptom improvement to occur
Intraluminal brachytherapy
May be used as the sole therapy for palliation of malignant dysphagia
Limited availability Frequent occurrence of post-
treatment strictures.
Newer forms of radiotherapy
Minimises radiation to other organs
Patient specific planning target volume (PTV) using cone beam computed tomography (CBCT) imaging is acquired in the first week of radiotherapy
14 patients have been studied
Needs further evaluation
Chemoradiation
Stent v/s brachytherapy
GASTROINTESTINAL ENDOSCOPY 2005
GASTROINTESTINAL ENDOSCOPY 2005
To summarize…Management Options for the Palliation of
Dysphagia
Management algorithm
Is there e/o TOF
Is there e/o TOF
Is there e/o TOF
Is there e/o TOF
Future perspectives Need for tumor markers to predict
response to therapy and survival
Intratumoral injection of cisplatin/epinephrine gel
Targeted therapy needs further evaluation
Future perspectives
Cone Beam Computed Tomography-Derived Adaptive Radiotherapy
Role of biodegradable stents needs to be defined further
Summary
Advanced but localized cancers: surgical resection
Cancers with regional lymphadenopathy: neoadjuvant chemotherapy and radiation therapy
Summary
Advanced unresectable disease: primary therapy with radiation and chemotherapy
Palliation of dysphagiaStentBrachytherapy
Thank you