FARSHAD SEYEDNEJAD, M.D ASSISTANT PROFESSOR TABRIZ MEDICAL SCIENCE UNIVERSITY RADIATIONS ONCOLOGY DEPARTMENT IMAM KHOMEINI HOSPITAL Managing Locally advanced Gastric and GE junction cancer

Introduction At diagnosis ,nearly 50% of pts have cancers that extents beyond locoregional . Fewer than 60% pts with locoregional can undergo curative resection. 70-80% resected specimens harbor met in regional lymph nodes. Clinicians often deals with advanced stage incurable carcinoma in newly diagnosed pts.

At diagnosis ,nearly 50% of pts have cancers that extents beyond locoregional .

Fewer than 60% pts with locoregional can undergo curative resection.

70-80% resected specimens harbor met in regional lymph nodes.

Clinicians often deals with advanced stage incurable carcinoma in newly diagnosed pts.

Surgery Gold standard for resected dis. Intent: Achieve R0 resection. Palliative resection should be avoided in pts with clearly unresectable or advanced . Recent randomized preop Cht/XRT (CALGB9781) & Preop Cht significantly improved survival in resectable GE junction.

Gold standard for resected dis.

Intent:

Achieve R0 resection.

Palliative resection should be avoided in pts with clearly unresectable or advanced .

Recent randomized preop Cht/XRT (CALGB9781) & Preop Cht significantly improved survival in resectable GE junction.

Principals of Surgery Selecting assessing whether they are medically fit & extent of their cancer. Esophageal resection : for all physiologically fit with localized resected thoracic (≥5 cm from cricopharyngeus) or GE. T1-T3 tumors are resectable even regional nodal met (N1). T4 with involvement of pericardium ,pleura or diaphragm . Stage IV lower esophagus with celiac nodes(1.5 cm or less)with no involvement of celiac artery ,aorta are resectable.

Selecting

assessing whether they are medically fit & extent of their cancer.

Esophageal resection :

for all physiologically fit with localized resected thoracic (≥5 cm from cricopharyngeus) or GE.

T1-T3 tumors are resectable even regional nodal met (N1).

T4 with involvement of pericardium ,pleura or diaphragm .

Stage IV lower esophagus with celiac nodes(1.5 cm or less)with no involvement of celiac artery ,aorta are resectable.

Radiation therapy Most series included pts with unfavorable features such as clinical T4. Overall 5 –year survival 0-10%. RTOG 8501 in RT alone 64GY at 2 Gy/d all pts died by 3 years. RT alone only for palliation or pts who are mediacally unable to receive chemotherapy. Alternate radiation approaches such as hypoxic sensitizers & hyper fraction have not result in clear survival advantage. Conformal & IMRT investigated. In adjuvant setting no survival benefit for Preop XRT alone. Esophageal cancer collaborative g roup

Most series included pts with unfavorable features such as clinical T4.

Overall 5 –year survival 0-10%.

RTOG 8501 in RT alone 64GY at 2 Gy/d all pts died by 3 years.

RT alone only for palliation or pts who are mediacally unable to receive chemotherapy.

Alternate radiation approaches such as hypoxic sensitizers & hyper fraction have not result in clear survival advantage.

Conformal & IMRT investigated.

In adjuvant setting no survival benefit for Preop XRT alone.

Esophageal cancer collaborative g roup

brachytherapy BRT alone is palliative modality & result in local control 25-30% median survival 5 months. Randomized trial SUR no difference in local control or survival with XRT. RTOG 92-07 Additional benefit if adding BRT remains unclear.

BRT alone is palliative modality & result in local control 25-30% median survival 5 months.

Randomized trial SUR

no difference in local control or survival with XRT.

RTOG 92-07

Additional benefit if adding BRT remains unclear.

Chemoradiation therapy followed by surgery Although this approach is reasonable ,it remains investigational. Significantly increase 3 year survival compared to surgery alone. However postoperative mortality significantly increased. CALGB 9781 Prospective randomized intergroup trial :survival benefit Preop cht/xrt followed surgery is most common approach for pts with resectable esophageal cancer. in pts with advanced unresectable ,cht/xrt can facillaite surgical resection in selected case. For nonsurgical candidates definitive Chemoradiation is also an appropriate option.

Although this approach is reasonable ,it remains investigational.

Significantly increase 3 year survival compared to surgery alone.

However postoperative mortality significantly increased.

CALGB 9781

Prospective randomized intergroup trial :survival benefit

Preop cht/xrt followed surgery is most common approach for pts with resectable esophageal cancer.

in pts with advanced unresectable ,cht/xrt can facillaite surgical resection in selected case.

For nonsurgical candidates definitive Chemoradiation is also an appropriate option.

Chemotherapy followed by surgery Intergroup 0113 No survival benefit . Medical research council(MRC): 3.5 months survival time advantage. NCCN Panel: Dose not recommend preop or postop cht over surgery alone.

Intergroup 0113

No survival benefit .

Medical research council(MRC):

3.5 months survival time advantage.

NCCN Panel:

Dose not recommend preop or postop cht over surgery alone.

Surgery followed by Chemoradiation therapy McDonald : Survival benefit in stomach & GE junction. 36 months vs. 27 months. Postoperative cht/xrt significantly improved overall survival & relapse free for all pts at high risk for recurrence of adenoca. stomach & GE junction.

McDonald :

Survival benefit in stomach & GE junction.

36 months vs. 27 months.

Postoperative cht/xrt significantly improved overall survival & relapse free for all pts at high risk for recurrence of adenoca. stomach & GE junction.

result Medically fit with resectable(T1-T4,N0-1 or stage IVA): 3 option for primary : Esophagectomy followed by adjuvant Chemoradiation. Preop concurrent Chemoradiation followed by esophagectomy. Definitive Chemoradiation followed by observation or salvage surgery. Adjuvant treatment following margin negative (RO): Based on nodal & histology T1-2 NO :observation T3 NO &selected T2 high risk(poor diff, younger ,lymphovascular or neurovascular): Chemoradiation . Scc observed irrespective of their nodal status. Adeno positive nodes : Observation or Chemoradiation. Location (McDonald) ::Chemoradiation. R1-2 :chemoradiation

Medically fit with resectable(T1-T4,N0-1 or stage IVA):

3 option for primary :

Esophagectomy followed by adjuvant Chemoradiation.

Preop concurrent Chemoradiation followed by esophagectomy.

Definitive Chemoradiation followed by observation or salvage surgery.

Adjuvant treatment following margin negative (RO):

Based on nodal & histology

T1-2 NO :observation

T3 NO &selected T2 high risk(poor diff, younger ,lymphovascular or neurovascular): Chemoradiation .

Scc observed irrespective of their nodal status.

Adeno positive nodes :

Observation or Chemoradiation.

Location (McDonald) ::Chemoradiation.

R1-2 :chemoradiation