Clinical Target Volume (CTV) delineation manual for the CRITICS gastric cancer study

2nd revised edition- January 2008

Edwin P.M. Jansen, MD PhD Emmy Lamers, MSc Marcel Verheij, MD PhD The Netherlands Cancer Institute Dept. of Radiotherapy Plesmanlaan 121 1066 CX Amsterdam The Netherlands epm.jansen@nki.nl

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Authors: Edwin P.M. Jansen, MD PhD Emmy Lamers, MSc Marcel Verheij, MD PhD Clinical Target Volume (CTV) delineation manual for the CRITICS gastric cancer study © 2008, E.P.M. Jansen, E. Lamers, M. Verheij Published in-house The Netherlands Cancer Institute Department of Radiotherapy Plesmanlaan 121 1066 CX Amsterdam The Netherlands epm.jansen@nki.nl All rights reserved. No part of this publication may be translated, reproduced, stored in a retrieval system, or transmitted in any form by any means, electrical, mechanical, photocopying, recording, broadcasting or otherwise, without prior permission from the publisher. This publication shall not constitute any obligations. Medical knowledge is constantly changing. It is the responsibility of the practitioner, relying on experience and knowledge of the patient, to determine the best treatment for each individual patient. The authors do not assume any liability for any injury and/or damage to persons or property arising from this publication.

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Introduction This Clinical Target Volume (CTV) manual is an integrative part of the CRITICS (Chemoradiotherapy after induction chemotherapy in cancer of the stomach) phase III multicenter trial. Its main emphasis is to help the radiation oncologist in constructing a CTV and to facilitate decreasing inter- and intraobserver variability in delineation of a CTV in gastric cancer radiotherapy. Although we consider individualization of CTV’s with respect to primary tumor location, type of surgery and lymph node metastatic patterns potentially to be of great benefit (less toxic), we also believe that very complex delineation protocols will not be of great help. Additionally, with the introduction of more conformal radiotherapy techniques like IMRT, we think that too strict guidelines could lead to more marginal misses in radiotherapy. Therefore, this manual consists of guidelines and practical tools that will help the radiation oncologist to construct an adequate CTV. The guidelines in this manual can be interpreted as a minimum requirement for defining a CTV. Furthermore, these guidelines can be seen as a starting point. When CT-based CTV contouring has become daily practice in more institutions, modifications to these guidelines can be introduced, preferably based on clinical studies. 1) A postoperative diagnostic CT with oral and i.v. contrast is needed to identify:

• esophagus and gastric remnant • anastomosis (staple lines) • duodenal stump • porta hepatis • splenic hilum • pancreas • celiac and superior mesenteric artery

Furthermore for defining the CTV the following info is needed:

Preoperative CT Preoperative endoscopy report Postoperative CT with contrast (see above) Pathology report Surgical report

2) A single CTV is contoured per CT slice. Not every slice has to be contoured, interpolation can be used when CTV’s are delineated each 10 mm. Furthermore liver, kidneys, heart and spinal cord should be contoured.

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The CTV consists of 3 parts:

1. anastomoses 2. gastric bed/ remnant 3. lymph nodes

ad1) Anastomoses:

• duodenal stump has to be treated in tumors of the distal stomach

• for tumors of the proximal stomach or GE-junction, the oesophagojejunal anastomosis has to be treated Cave: for GE-junction tumors a margin of 4cm (!) of oesophagus (paraoesophageal nodes) has to be included in the CTV

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ad2) Gastric remnant and tumor bed:

• GE and proximal tumors at least 2/3-3/4 of the left medial hemidiaphragm

• T1-2 tumors tumor bed not necessarily

• hepatogastric ligament (i.e. part of lesser omentum between liver and lesser curvature, which contains peri-gastric nodes)

• anterior abdominal wall: only in T3-4 tumors with invasion or a close relationship with the anterior abdominal wall on pre-operative imaging or when described by the surgeon durante operatione

green = hepatogastric ligament red = lymphnode st 5

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ad3) Which lymphnodes have to be included in the CTV? individualize for GE-junction/Cardia (proximal), Corpus (middle) and antrum (distal) tumors

GE-junction/ Cardia/proximal 1/3

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Regional lymphatics

JAPANESE CLASSIFICATION Lymph node stations surrounding the stomach. 1, right cardial nodes 2, left cardial nodes 3, nodes along the lesser curvature 4, nodes along the greater curvature 5, suprapyloric nodes 6, infrapyloric nodes 7, nodes along the left gastric artery 8, nodes along the common hepatic artery 9, nodes around the celiac axis 10, nodes at the splenic hilus 11, nodes along the splenic artery 12, nodes in the hepatoduodenale ligament 13, nodes at the posterior aspect of the pancreas head 14, nodes at the root of the mesenterium 15, nodes in the mesocolon of the transverse colon 16, para-aortic nodes.

: para-oesophageal, perigastric, hepatogastro lig, perigastric, ,celiac (left gastric artery, celiac axis), splenic hilum, suprapancreatic, porta hepatis, pancreaticoduodenal [stations 1-4;7,9-13]

Corpus/middle 1/3 : perigastric, suprapyloric, infrapyloric, celiac (left gastric artery, common hepatic artery and celiac axis), splenic hilum, suprapancreatic, porta hepatis, pancreaticoduodenal [stations 3-13]

• Antrum/distal 1/3: perigastric, suprapyloric, infrapyloric, splenic artery, pancreaticoduodenal, porta hepatis, celiac (left gastric artery, common hepatic artery and celiac axis), suprapancreatic [stations 3-9;11-13] + all combinations when tumor invaded more than one part of the stomach before start of treatment

Tepper et al . (2002)

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Lymph nodes per station (according to Japanese classification) These lymph node stations are contoured by a GI-radiologist from the Netherlands Cancer Institute. The most cranial, the middle and the most caudal contour of each station are depicted. For anatomical purposes this has been done in a CT with contrast of a patient with his stomach in situ. In all CT’s the lymph node area is contoured in red and the stomach in blue.

Lymph node station 1 (right paracardial)

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Lymph node station 2 (left paracardial)

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Lymph node station 3 (along the lesser curvature)

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Lymph node station 4 (along the greater curvature)

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Lymph node station 5 (pyloric, suprapyloric)

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Lymph node station 6 (infrapyloric)

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Lymph node station 7 (along left gastric artery)

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Lymph node station 8 (along common hepatic artery)

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Lymph node station 9 (celiac axis)

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Lymph node station 10 (splenic hilus)

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Lymph node station 11 (along the splenic artery)

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Lymph node station 12 (hepatoduodenal ligament)

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Lymph node station 13 (posterior aspect pancreatic head)

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Lymph node station 14 (root of the mesenterium)

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Lymph node station 15 (mesocolon)

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Lymph node station 16 (para-aortic)

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Based on preoperative position of stomach, localization of primary tumor (proximal, middle or distal) and the lymph node stations that should be in the CTV, the following 3 typical compository clinical target volumes can be constructed. For each individual case, the effects of surgery on abdominal anatomy should be accounted for. For example, colon that fills up the surgical cavity after surgery is not part of the CTV per se. This will be shown on CT images of the same patient after gastric surgery at the end of this manual. 1) Typical example of a CTV for a proximal gastric cancer (PRE-OPERATIVE); interval

between slides is 1cm:

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2) Typical example of a CTV for a middle gastric cancer(PRE-OPERATIVE) interval between slides is 1cm:

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3) Typical example of a CTV for a distal gastric cancer (PRE-OPERATIVE) interval between slides is 1cm:

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Typical CTV’s in the post-operative setting: 1) Proximal gastric cancer (purple is matched CTV from preop CT; green is adapted

CTV postoperative)

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2) Middle gastric cancer (blue is matched CTV from preop CT; green is adapted CTV postoperative)

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3) Distal gastric cancer (purple is matched CTV from preop CT; green is adapted CTV postoperative)

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© PTV After construction of a CTV a margin for defining the planning target volume (PTV) has to be chosen. This margin should correct for daily setup variation and organ motion (random deviation) and for suboptimal localization and delineation of CTV (systematic deviation). Because these deviations will differ per radiotherapy department, no general rules can be given. The margins will have to be based on departmental policies, on information on measurements on setup variation and on radiotherapy technique used (3D conformation or IMRT). 4D information in internal organ movement (diaphragm, gastric remnant) when available, should be used in treatment planning and delivery (4D CT simulation; cone beam CT) When this information is not available, as a general rule, a margin of 10 mm could be used for expanding the CTV to the PTV.

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SWOG/Intergroup CTV guidelines (Tepper et al. 2002)

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Literature

Tepper JE, Gunderson LL. Radiation treatment parameters in the adjuvant postoperative therapy of gastric cancer. Semin Radiat Oncol 2002; 12: 187-195

Trans-Tasman Radiation Oncology Group. A feasibility study to evaluate adjuvant chemoradiotherapy for gastric cancer. 2003

Japanese research society for gastric cancer. The general rules for the gastric cancer study in surgery and pathology. Jpn J Surg 1981; 11:127-139

Martinez-Monge R, Fernandes PS, Gupta N et al. Cross-sectional nodal atlas: a tool for the definition of clinical target volumes in three-dimensional radiation treatment planning. Radiology 1999; 211: 815-828

Smalley SR, Gunderson L, Tepper J et al. Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 2002; 52: 283-293

Southwest Oncology Group 9008/ Intergroup. Trial of adjuvant chemoradiation after gastric resection for adenocarcinoma. Phase III. 1991