CERVIX TARGET VOLUME DELINEATION GUIDELINES

Purpose: For definitive treatment of carcinoma cervix with conformal radiation techniques, accurate target delineation is vitally important, yet a consensus definition of clinical target volume (CTV) remains variable within the literature.

Objectives:

• Review guidelines for CTV delineation published in the literature
• Present guidelines practiced at PGIMER institute
• Provide complete set of guidelines for delineating both CTV primary and CTV nodal in combination

Traditional vs. Modern Approach:

• Traditional: Four-field box technique defined by bony landmarks
• Modern: 3D conformal radiotherapy with CT-based planning
• Advantages: Reduced toxicity, improved target coverage, decreased geographic miss

Source: Bansal A, Patel FD, et al. J Cancer Res Ther 2013;9:574-82

Patient Preparation

• Fasting minimum 4 hours prior to planning CT scan
• Oral contrast: 20 ml urograffin dissolved in 1 litre water given over 1 hour before CT scan
• Rectal contrast: 20 ml urograffin in 50 ml normal saline
• Patient asked to void urine 15 minutes prior to CT
• Consistent bladder filling protocol: voiding 15 min prior to both imaging and treatment

Positioning & Scanning

• Patient positioned supine on couch in CT simulator
• Knee wedge used as positioning device for reproducibility
• Intravenous contrast: 100 ml omnipaque (Cross method)

Scan Parameters

• Scan range: T10-T11 interspace to upper third of femur
• Slice thickness: 3.75 mm
• Images transferred to Eclipse TPS workstation

OAR includes:

• Bowel
• Bladder
• Rectum
• Bone marrow

Contouring according to RTOG normal tissue contouring guidelines

CTV 1 includes: Involved nodes and relevant draining nodal groups (common iliac, internal iliac, external iliac, obturator and presacral LN)

PGI Protocol Summary (Modified Taylor Guidelines)

Step	Delineation Instruction
1	Start contouring iliac vessels from aortic bifurcation down till the appearance of femoral head
2	Uniformly, pelvic blood vessels are given a margin of 7mm; upper border maintained at aortic bifurcation
3	Contour extended around common iliac vessels posteriorly and laterally to include connective tissue between iliopsoas muscles and lateral surface of vertebral body
4	No additional 10mm anterolateral extension around external iliac vessels along iliopsoas muscle
5	For obturator nodes: Create 17 mm wide strip medial to pelvic sidewall by joining external iliac vessels with internal iliac vessels. Continue along pelvic side wall till superior part of obturator foramen
6	Posterior margin of CTV 1 over internal iliac vessels lies along anterior edge of piriformis muscle
7	Pre-sacral region: Connect volumes on each side of pelvis with 10-mm strip over anterior sacrum from aortic bifurcation till S2-S3 junction. Sacral foramina NOT included
8	All visible nodes (GTV node) given 10mm margin to create CTV node and included in CTV 1
9	Muscle and bone excluded from CTV 1

Rationale for Modifications from Original Taylor Guidelines

• No anterolateral extension: Lateral external iliac nodes rarely involved (3.8% in Stage III). Medial groups are main drainage from cervix/upper vagina
• Starting at aortic bifurcation: PGI study showed 48/50 patients had aortic bifurcation above L4-L5; conventional fields led to median miss of 2.95 cm at superior border
• 10mm margin on visible nodes: Follows ICRU guidelines for CTV margin over GTV

CTV 2 comprises: Uterine corpus, entire cervix, vagina, and gross disease (GTV primary) contoured as a single structure

Uterus Contouring

• Include entire uterine corpus and cervix
• Rationale: Uterus and cervix are embryologically one unit with interconnected lymphatics
• No clear separating fascial plane exists

Vagina Inclusion Guidelines

Vaginal Involvement	Extent Included in CTV 2
Minimal or no involvement	Stop 4 slices above lower border of obturator foramen (so 1.5 cm ITV margin doesn't extend beyond obturator foramen)
Upper vaginal involvement	Upper two-thirds of vagina
Extensive vaginal involvement	Entire vagina (based on MRI and clinical examination with vaginal marker)

Paravaginal tissue: Included along with vaginal wall

Definition: Connective tissue extending from cervix to pelvic wall, including visible linear structures (vessels, nerves, fibrous structures)

Parametrial Boundaries

Border	Anatomical Landmark
Cranial	Level where true pelvis begins
Anterior (central)	Posterior border of bladder
Anterior (peripheral)	Anterior end of lateral pelvic bony wall
Lateral	Lateral pelvic wall, up to medial edge of internal obturator muscle
Caudal	Medial border of levator ani or pelvic floor

Posterior Boundary (Stage-Dependent)

Patient Category	Posterior Extent
FIGO Stage ≥III B OR Clinical/radiological involvement of uterosacral ligaments OR Extensive nodal involvement	Extend to rectal contour to include entire mesorectum and uterosacral ligaments
All other patients (Early stage without above features)	Contour only till anterior semicircular part of mesorectal fascia

Ovaries

• Ovaries visible on CT are included within CTV 3
• Ovarian metastasis rates: 0.5% (SCC) to 2.4% (adenocarcinoma) in early stage
• Consider excluding in selected cases (non-bulky Stage I/II with SCC)

Purpose: Account for uterine motion during treatment

Literature on Uterine Motion

• Maximum inter-fraction displacement: up to 36 mm (fiducial marker studies)
• Superior movement: median 4-7 mm (empty vs. full bladder)
• Range: up to 45mm supero-inferior, 28mm antero-posterior
• Mean displacement: 7mm antero-posterior and supero-inferior (MRI studies)

PGI ITV Margin (Applied to CTV 2 - Uterus)

Direction	Margin
Antero-posterior	15 mm
Supero-inferior	15 mm
Lateral	7 mm

Note: This asymmetrical expansion accounts for greater uterine mobility in antero-posterior and supero-inferior directions

Total CTV Construction

• Total CTV = CTV 1 (nodal) + CTV Primary (CTV 2 + CTV 3)

PTV Margin (Setup Uncertainty)

• Standard margin: 10 mm all around Total CTV
• Can be reduced with robust immobilization and daily CBCT/IGRT

Final PTV

• Final PTV = Total PTV + ITV margin over CTV 2
• Margin from uterine surface: 15mm antero-posterior and supero-inferior (same as ITV)
• Final PTV manually/automatically trimmed up to 3mm from skin surface if necessary (ensuring CTV still fully included)

Summary Workflow

1. CTV 1 (nodal) + CTV 2 (uterus) + CTV 3 (parametrium) = Total CTV
2. Total CTV + 10mm = Total PTV
3. CTV 2 + ITV margin (15/15/7mm) = accounts for uterine motion
4. Total PTV + ITV = Final PTV to be treated

Comparison of Major Guidelines

Parameter	Taylor et al.	Small et al.	Toita et al.	Lim et al.	PGI Guidelines
Vessel margin	7mm	7mm	7mm	7mm	7mm
Superior border	Aortic bifurcation	L4-L5 (RTOG)	Aortic bifurcation	-	Aortic bifurcation
Anterolateral EI extension	Yes (10mm)	No	No	-	No
Obturator width	17mm strip	-	Defined by anatomy	-	17mm strip
Visible node margin	Included in 7mm	Included	-	-	10mm
Parametrium cranial border	-	-	Uterine isthmus	Top of fallopian tubes	True pelvis begins

Unique Features of PGI Guidelines

• First report providing complete combined CTV primary + CTV nodal guidelines
• Evidence-based modifications from institutional recurrence patterns
• Emphasis on aortic bifurcation as superior border (not L4-L5)
• Specific ITV margins based on uterine motion studies
• Stage-dependent parametrial posterior boundary

PGI Institutional Data

• Conventional four-field box study (50 patients): Only 2/50 had complete target volume coverage
• Geographic miss with L4-L5 border:
  • 48/50 patients: Aortic bifurcation above L4-L5
  • Median miss: 2.95 cm at superior border
  • Maximum miss: up to 7.27 cm
• Recurrence patterns:
  • 3/50 local recurrence, 3/50 lymph node recurrence (median 6 months)
  • All nodal recurrences were above L4-L5 junction (below aortic bifurcation)
  • No in-field pelvic or inguinal nodal recurrence

Literature Evidence - Beadle et al. (180 patients)

• Conventional fields with upper border at L4-L5
• 66% (119/180) had component of marginal failure
• 42% (75/180) had marginal recurrence without in-field recurrence
• Of 75 marginal failures: 71 patients had above-field recurrence only

Advantages of 3D-CRT/IMRT

• Reduced acute and late toxicity
• Improved pelvic nodal coverage
• Decreased geographic miss
• Ability to spare normal tissues (bowel, bladder, bone marrow)
• Dose escalation potential

Primary Source:

Bansal A, Patel FD, Rai B, Gulia A, Dhanireddy B, Sharma SC. Literature review with PGI guidelines for delineation of clinical target volume for intact carcinoma cervix. J Cancer Res Ther 2013;9:574-82.

Key References Reviewed:

• Taylor A, Rockall AG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: Guidelines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:1604-12.
• Taylor A, Rockall AG, Powell ME. An atlas of the pelvic lymph node regions to aid radiotherapy target volume definition. Clin Oncol 2007;19:542-50.
• Small W Jr, Mell LK, Anderson P, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer. Int J Radiat Oncol Biol Phys 2008;71:428-34.
• Toita T, Ohno T, Kaneyasu Y, et al. A consensus-based guideline defining the clinical target volume for pelvic lymph nodes in external beam radiotherapy for uterine cervical cancer. Jpn J Clin Oncol 2010;40:456-63.
• Lim K, Small W Jr, Portelance L, et al. Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer. Int J Radiat Oncol Biol Phys 2011;79:348-55.

Background:

• Implementation of advanced 3D radiotherapy planning requires accurate target volume localisation
• Pelvic lymph node irradiation has important role in management of many pelvic malignancies
• IMRT shows significant dosimetric advantages over conventional approaches
• Lack of consensus on target volume has limited widespread implementation

Challenge:

• Most normal-size lymph nodes too small to be directly visualised on standard imaging
• Nodal size criteria (≥10mm) has only 40-70% sensitivity for metastases
• Unenlarged nodes may contain tumor deposits
• Need to include all lymph nodes within draining regions in CTV

Solution Approach:

• Anatomical studies show pelvic lymph nodes lie adjacent to major pelvic blood vessels
• Use blood vessels as surrogate target with appropriate margins
• USPIO (Ultra-Small Particles of Iron Oxide) MRI studies validate vessel-based approach

Aim: Develop a generic CT atlas showing position of pelvic lymph nodes for 3D radiotherapy planning

Source: Taylor A, Rockall AG, Powell MEB. Clin Oncol 2007;19:542-550

Patient & Scanning

• Patient: Postoperative radiotherapy case (simple abdominal hysterectomy and bilateral salpingo-oophorectomy for uterine cancer)
• Position: Supine with full bladder
• Scan range: 2 cm above aortic bifurcation to lower limit of inguinal region
• Slice thickness: 5 mm intervals
• Contrast: Intravenous contrast given to aid vessel visualisation
• Planning system: Eclipse v6.5 (Varian)

Delineation Protocol

• Blood vessels used as surrogate target for lymph nodes
• Initial 7mm margin drawn around pelvic blood vessels
• Specific modifications applied to different nodal regions (see detailed guidelines)

Lymph Node Group	Recommended Margins
Common Iliac	7mm margin around vessels Extend posterior and lateral borders to psoas and vertebral body
External Iliac	7mm margin around vessels Extend anterior border by further 10mm anterolaterally along iliopsoas muscle to include lateral external iliac nodes
Internal Iliac	7mm margin around vessels Extend lateral borders to pelvic side wall
Obturator	Join external and internal iliac regions with 17mm wide strip along pelvic side wall
Pre-sacral (Subaortic)	10mm strip over anterior sacrum
Pre-sacral (Mesorectal)	Cover entire mesorectal space
Visible Nodes	Also include any visible nodes (≥8mm diameter readily identified on CT)

Delineation Steps

• Draw 7mm margin around common iliac vessels
• Extend posteriorly: To vertebral body
• Extend laterally: Pass around psoas muscle
• This encompasses connective tissue at risk of nodal involvement

Clinical Indications

• Cervical cancer: Always include
• Other gynecological cancers: Include when lymphadenopathy present in another pelvic region

Anatomical Note

Common iliac nodes are first-echelon drainage for cervical cancer, making them essential elective target volume

Standard Delineation

• 7mm margin around external iliac vessels
• Continue until vessels pass through inguinal ligament

Lateral External Iliac Nodes (Special Consideration)

Additional 10mm anterolateral extension: Along iliopsoas muscle to cover distal lateral external iliac nodes

Evidence on Lateral Nodes

• Often lie distant from vessels
• Missed by conventional fields in 34-45% of cases
• However, rare site of recurrence

Recommendation for Lateral Extension

Include ONLY if:

• Other external iliac lymph nodes involved, OR
• Target volume also includes inguinal regions

Routine inclusion NOT recommended (can be omitted in most cases)

Delineation

• 7mm margin around internal iliac vessels
• Lateral borders: Extend to pelvic side wall

Clinical Importance

• Key drainage pathway for pelvic gynecological malignancies
• Routinely included in CTV for cervical cancer

Delineation Method

• Join external iliac and internal iliac regions
• Create strip: 17mm wide along pelvic side wall
• This strip medial to pelvic sidewall encompasses obturator nodes

Anatomical Rationale

• Obturator nodes lie in space between external and internal iliac vessels
• 17mm width ensures adequate coverage
• Important nodal station for cervical and endometrial cancer

Subaortic Pre-sacral Nodes

• Method: 10mm strip over anterior sacrum
• Location: Connects volumes on each side of pelvis anteriorly over sacral prominence
• Routinely included in standard pelvic fields

Lower Pre-sacral/Mesorectal Nodes

Cover entire mesorectal space when:

• Tumor extension along uterosacral ligaments present, OR
• Rectal involvement present

Otherwise: Not routinely included

Exclusions from CTV

• Muscle: Delete where margin passes over muscle
• Bone: Delete where margin passes over bone

Pathologically Enlarged Nodes

• Nodes ≥8mm diameter readily identified on CT
• Critical: Ensure all visible nodes fully encompassed by CTV
• Guidelines apply to normal-sized nodes; enlarged nodes must be individually covered

Parametria & Vaginal Vault

• Outlined as separate structure in adjuvant setting
• Combined with nodal CTV for total pelvic target volume

Gynecological Cancers - Typical CTV

Tumor Site	Nodal Groups Included
Cervical Cancer	• External iliac • Internal iliac • Obturator • Common iliac (always) • Pre-sacral (if uterosacral/rectal involvement)
Endometrial Cancer	• External iliac • Internal iliac • Obturator • Common iliac (if lymphadenopathy elsewhere) • Pre-sacral (if rectal involvement)
With Inguinal Treatment	Add: • Inguinal nodes • Distal lateral external iliac nodes

IMRT Advantage

Complexity of dose patterns with IMRT allows selective coverage of nodal groups based on tumor site and stage - enables individualized treatment planning

USPIO-MRI Studies

• Method: Ultra-small particles of iron oxide make lymph nodes readily visible on MRI
• Finding: 7mm margin around vessels achieved 88% nodal coverage
• Validation: Guidelines independently applied to further patient series
• Result: Effective in ensuring target volume coverage for >99% of nodes

Anatomical Basis

• Pelvic lymph nodes lie adjacent to major pelvic blood vessels
• Vessels relatively well visualised on conventional imaging
• Appropriate margins around vessels serve as effective surrogate for lymph node regions

Benefits of Atlas Approach

• Standardisation of target volumes for IMRT
• Consistent and accurate target volume definition
• Reduced inter-observer variability
• Educational tool for training

Extrapolation to Other Sites

While atlas shows CTV for gynecological cancer, reasonable to extrapolate to:

• Male pelvic anatomy
• Urological cancers requiring pelvic nodal treatment
• Similar target volumes with site-specific modifications

Need for Ongoing Data Collection

• Prospective data on sites of pelvic recurrence in IMRT-treated patients
• Functional imaging integration (PET, advanced MRI)
• Sentinel lymph node study results
• Future refinement/individualisation of target volumes

Geographic Miss Prevention

• Greater conformity in all dimensions with IMRT
• Salvage rarely successful after geographic miss
• Standardised guidelines critical for avoiding marginal recurrences

Core Principles

• 7mm vessel margin is fundamental for all nodal groups
• Anatomical modifications specific to each nodal region ensure comprehensive coverage
• Clinical context determines which nodal groups to include
• Visible nodes must be individually verified for complete coverage

Quick Reference Summary

Region	Key Feature
Common iliac	Extend to psoas & vertebral body
External iliac	±10mm lateral extension (selective)
Internal iliac	Extend to pelvic side wall
Obturator	17mm strip joining EI & II
Pre-sacral	10mm strip ± mesorectal space

Primary Source:

Taylor A, Rockall AG, Powell MEB. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology 2007;19:542-550.

Previous Work by Authors:

Taylor A, Rockall AG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: guidelines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:1604-1612.

Validation Study:

Vilarino-Varela MJ, Taylor A, Rockall AG, et al. Whole pelvis IMRT: verification of guidelines for lymph node delineation. Clin Oncol 2005;17(Suppl. 1):3-4.

Acknowledgements:

Research supported by X-Appeal fund, Royal College of Radiologists and BUPA Foundation, UK.