TSET - Total Skin Electron Therapy in Radiotherapy

What is TSET?

Indications

• Sézary syndrome (leukemic variant of CTCL)
• Leukemia cutis (cutaneous leukemia involvement)
• Other highly radiosensitive hematologic malignancies with widespread skin involvement

• Stages IIB, III, IV mycosis fungoides
• Disease that has failed less aggressive therapies (phototherapy, topical alkylating agents, oral retinoids)
• Stage IIA/IB as a second-line option (Level 2 evidence)

• Dermatology 2-Volume Set 5e, p. 2867 | EORTC 2024 guidelines

Physical Principle

• Radiation dose is concentrated in the superficial skin (~1-2 cm depth)
• Bone marrow and viscera receive essentially no significant dose
• The technique avoids systemic radiation toxicity

Technical Setup

The Stanford Six-Field Technique

Areas Requiring Supplemental Boosts

• Scalp
• Perineum
• Plantar surface (soles of feet)
• Tumor-stage lesions (supplemental boosts at completion of TSEBT)

Shielding

• Eyes: Lead contact lenses (mandatory)
• Hands and feet: May be shielded for a portion of the treatment cycle depending on total anticipated dose
• Thin areas (fingers, toes) that would be overdosed get lead shielding halfway through treatment

Dosing Regimens

Historical (High-Dose) Regimen

• 30-36 Gy total dose over 9-11 weeks
• Small daily fractions, 4 treatments/week
• Treatment break of 1-2 weeks typically needed midway (for skin recovery)
• Could only be repeated once
• Complete response rate: ~72% (early stage), ~55% (advanced stage); overall response ~100% for early stage

Modern (Low-Dose) Regimen - Now Preferred

• 10-12 Gy total dose over 3 weeks
• Excellent response rates (~90%)
• Can be repeated up to 6 times - offering comparable or better palliation overall
• Most patients now receive low-dose TSET; higher doses reserved for resistant disease

Response Rates

Side Effects

Acute/Subacute

• Erythema (skin redness) - common
• Blisters and skin pain
• Skin desquamation

Late/Permanent Effects (more common with higher-dose regimens)

• Alopecia (hair loss) - may be permanent
• Dyspigmentation (skin color changes)
• Hypohidrosis (reduced sweating) - can be permanent
• Nail changes

What Does NOT Occur (unlike systemic radiation)

• Cytopenias (no significant bone marrow dose)
• Nausea, vomiting, diarrhea
• Systemic organ toxicity

Repeat Treatment

• Interval between courses >6 months
• Longer disease-free interval after the first course
• With low-dose regimens, up to 6 repetitions are feasible

Comparison with Other Approaches

Summary

Total Body Irradiation (TBI) - Technique and Treatment Verification

1. Overview and Purpose

Indications

• Acute lymphoblastic leukaemia (ALL)
• Acute myeloid leukaemia (AML)
• Lymphoma (Hodgkin and non-Hodgkin)
• Myelodysplastic syndromes (MDS)
• Chronic myeloid leukaemia (CML)
• Other haematological malignancies

Goals of TBI

1. Myeloablation - destroy residual malignant cells in bone marrow
2. Immunosuppression - prevent rejection of donor stem cells
3. Eradicate disease from sanctuary sites (CNS, testes, spleen)

2. Fractionation Schemes

3. Equipment Requirements

• Linear accelerator (LINAC) with high-energy photon beams: typically 6 MV (preferred over higher energies to avoid underdosing superficial bones such as the sternum and iliac crest)
• 4-18 MV beams acceptable per AAPM guidelines
• Machine must be capable of low dose rate (LDR) delivery: 5-20 cGy/min (reduces pneumonitis risk vs standard ~300-600 cGy/min)
• Extended Source-to-Surface Distance (SSD): typically 350-500 cm (e.g., 463 cm at Penn State) - necessary to produce a field large enough to cover the full body
• A backup LINAC should be designated in advance (critical, as patients cannot interrupt their transplant conditioning)
• Dedicated TBI room with sufficient space for extended SSD

4. Patient Positioning Techniques

A. Lateral Decubitus (Bilateral Horizontal Beam)

• Patient lies on their side (left and right lateral positions)
• Horizontal beam enters from the side
• Most common for adults
• Allows AP body thickness compensation

B. Supine/Prone (AP-PA Technique)

• Patient lies flat, treated AP then PA (rotated 180°)
• AP/PA direction provides better dose uniformity than lateral
• May use a treatment couch or stand

C. Standing Position (Vertical Beam)

• Patient stands upright against a board
• Used in some centers with a vertical beam
• More practical for some patients but requires good immobilization

D. Pediatric Patients

• Children who cannot cooperate may require general anesthesia
• Usually treated in lateral position
• Smaller body - separate commissioning/dosimetry may be required

Key Positioning Principles

• Patient's coronal midline aligned with the treatment plane marked on the floor at commissioning
• Immobilization devices (TBI stand, boards, custom supports) used
• Knees may be flexed to fit within the field if height is a limitation
• Compensators or field extensions used for extremities if needed

5. Dosimetry and Beam Configuration

Extended SSD Setup

Dose Prescription Point

• Typically at the midplane at the level of the umbilicus
• Patient thickness measured here for TMR calculation
• Target: dose homogeneity within ±10% across the whole body

Dose Rate

• Standard rate: ~300 cGy/min (conventional)
• Low dose rate: 5-20 cGy/min - strongly preferred for TBI to reduce pneumonitis
• Lower dose rate = more normal tissue repair capacity, reduced pulmonary toxicity

6. Organ at Risk (OAR) Shielding

Lung Shielding (Most Critical)

• Lungs are the dose-limiting organ in TBI - pneumonitis is the most serious complication
• Lead or low-melting alloy (Cerrobend) attenuators placed over the lungs
• Shields reduce lung dose by 10-50% (over-shielding risks leukemic relapse)
• Lung shield design accounts for: lung thickness, size, and density
• Shields can be tailored to avoid shielding: thymus, hilum, thoracic vertebrae, and heart
• In non-myeloablative / low-dose TBI regimens, lung shielding is usually omitted

Kidney Shielding

• Applied to reduce risk of bone marrow transplant nephropathy (hypertension, proteinuria, decreased GFR)
• Kidneys shift inferiorly when going from supine to standing - shields must be designed from scans in the actual TBI position
• At Cleveland Clinic: IV urogram in the standing position at 5, 10, and 15 minutes used to define kidney position for block design
• Kidney blocks are standard in many centers since kidneys are not a sanctuary site for leukaemia

7. Modern Techniques

A. Classical 2D TBI (Extended SSD, Parallel Opposed Fields)

• Two lateral or AP/PA opposed fields at extended SSD
• Simple but limited dose homogeneity (~±10%)
• Most widely used globally

B. Helical Tomotherapy TBI

• Patient moves through the helical tomotherapy ring in multiple passes
• Improved dose homogeneity
• Better OAR sparing
• Longer treatment time

C. VMAT-TBI (Volumetric Modulated Arc Therapy)

• Multiple isocenter VMAT arcs covering different body segments
• Superior dose conformality and OAR sparing vs 2D TBI
• A 2024 Stanford study confirmed VMAT-TBI improves toxicity outcomes compared to 2D TBI, with better lung and kidney sparing
• Plan quality metrics: PTV V100% ≥90%, V95% ≥95%, lung mean dose target <8 Gy
• QA: 3D phantom (ArcCHECK), Octavius 4D, gamma index 3mm/3%
• Not yet widespread but gaining adoption

D. Total Marrow Irradiation (TMI) / Total Lymphoid Irradiation (TLI)

• IMRT/VMAT-based targeted approach
• Treats only bone marrow ± lymphoid tissue
• Reduces dose to OARs by up to 75%
• Investigated for older/less fit patients who cannot tolerate standard TBI

8. Treatment Verification

• Field sizes and patient anatomy are highly non-standard
• Dose homogeneity across ±10% is a clinical requirement
• Errors can have serious consequences (graft failure, toxicity, relapse)

A. In-Vivo Dosimetry (Primary Verification Method)

• Midplane at umbilicus (prescription point)
• Neck/thyroid
• Head/vertex
• Chest/lung level
• Pelvis
• Knees and ankles (extremity verification)
• Hands (if not shielded)

B. Pre-Treatment Machine QA

C. Imaging and Setup Verification

• Port films / MV images to verify patient position and field coverage
• Lung block positioning verified on imaging before delivery
• Orthogonal images (AP + lateral) taken on first fraction

• kV CBCT (Cone Beam CT) or XVI at each isocenter
• Image registration to planning CT for each body segment
• Surface-guided radiotherapy (SGRT) systems (e.g., C-RAD Sentinel/Catalyst) used for intra-fraction motion monitoring
• Gamma index analysis (3mm/3% criteria) of VMAT plans using Octavius 4D or ArcCHECK phantom
• Point dose measurements at isocenter junctions (3 points per junction)

D. Phantom-Based Plan Verification (VMAT-TBI Specific)

• 3D ionization chamber/diode array phantom (ArcCHECK, SunNuclear) for full arc fluence measurement
• 2D array phantoms (PTW Octavius II / Octavius 4D)
• Gamma pass rate typically required: >95% at 3mm/3%
• Point dose measurements at junctions of isocenters to verify dose continuity

E. In-Vivo Dosimetry Workflow Summary

Pre-treatment:
  ├── Machine output check at TBI distance
  ├── Field size/flatness verification
  └── Phantom QA (VMAT) / Port films (2D TBI)

Per fraction:
  ├── Setup verification (imaging / SGRT)
  ├── Lung/kidney block position check
  ├── Patient position confirmation
  └── OSLDs/TLDs placed on skin surface

Post-fraction:
  ├── Read in-vivo dosimeters
  ├── Compare to planned dose (tolerance ±5%)
  └── Investigate and correct if outside tolerance

9. Complications and Their Dosimetric Basis

10. Summary: Key Points

• TBI uses parallel opposed high-energy photon fields at extended SSD (350-500 cm) to cover the entire body
• Standard dose: 12 Gy in 6 fractions (hyperfractionated, 2x/day), low dose rate (5-20 cGy/min)
• Dose homogeneity within ±10% is the primary physical goal
• Lung shielding (10-50% dose reduction) and kidney shielding are standard OAR protection strategies
• In-vivo dosimetry (OSLD/TLD) at multiple body points each fraction is the primary verification method - tolerance ±5% at prescription point
• VMAT-TBI is emerging as a superior technique with better OAR sparing, verified with CBCT, SGRT, and phantom QA (gamma index ≥95% at 3mm/3%)
• The AAPM TG-29 report provides standard guidelines for TBI dosimetry and prescription
• A 2024 Stanford publication confirmed VMAT-TBI significantly improves toxicity over conventional 2D TBI

Conventional Radiotherapy Technique for Carcinoma of the Oral Cavity

1. Overview

• Definitive RT: For early-stage disease (T1/T2) or patients unfit/refusing surgery
• Postoperative RT (PORT): Most common role - adjuvant after resection of advanced disease
• Palliative: For unresectable or metastatic disease

2. Patient Setup and Immobilization

Why the Tongue Depressor?

3. Treatment Energy and Machine

• Photon energy: 4-6 MV (preferred for head and neck; higher energies risk underdosing superficial lymph nodes and skin)
• Some centers use 6 MV as the standard energy
• Linear accelerator with MLC (multi-leaf collimator) for field shaping
• Source-to-skin distance (SSD): 80-100 cm (isocentric technique, SAD = 100 cm preferred)

4. Field Arrangement - The Classical Conventional Technique

A. Phase 1: Parallel Opposed Lateral Fields (Large Fields)

• Primary tumor + 2 cm margin
• Ipsilateral neck nodes: levels I, II, III (submandibular, jugulodigastric, mid-jugular)
• For T3/T4, or N+ disease: bilateral neck levels I-IV included

• The spinal cord is included in Phase 1 fields up to 40 Gy, then fields are reduced to spare it

B. Anterior Lower Neck Field (Matched Supraclavicular Field)

• For N+ disease or prophylactic lower neck coverage
• An anterior single field (AP) covering levels III-IV and the supraclavicular fossa
• Midline block over the larynx and trachea to reduce dose to the vocal cords and esophagus
• Matched (abutted) at the inferior border of the lateral fields using a half-beam block technique to avoid divergence overlap at the junction

C. Phase 2: Reduced "Off-Cord" Fields (After 40 Gy)

• Posterior electron fields: Direct electron beam (appropriate energy, typically 9-12 MeV) to the posterior cervical nodes that fall outside the reduced photon field
• Electrons chosen so the beam range stops anterior to the cord
• Matched carefully to avoid overdosing the junction with photon fields

D. Phase 3: Boost to Primary Tumor

• Reduces field to GTV + 1-1.5 cm margin
• Or brachytherapy boost (interstitial implant with Ir-192) if accessible lesion

5. Dose Fractionation

Definitive (Radical) RT

Postoperative RT (PORT)

6. Site-Specific Conventional Field Modifications

Floor of Mouth

• Parallel opposed lateral fields
• Tongue depressor used to exclude anterior mandible if not involved
• High risk of osteoradionecrosis of the mandible - minimize mandible dose

Oral Tongue (Anterior 2/3)

• Lateral opposed fields
• If lesion is well lateralized: may use wedged pair technique or ipsilateral oblique fields to spare contralateral salivary tissue
• Tongue depressor pulls tongue away from hard palate

Buccal Mucosa

• Lateral opposed fields OR intraoral cone + external beam combination
• Intraoral cone delivers orthovoltage/electrons directly to the lesion - "reverse boost" - reducing dose to surrounding mucosa
• External beam covers regional nodes subsequently

Retromolar Trigone

• Lateral fields with posterior extension
• Risk of temporal bone invasion - superior border adjusted
• Ipsilateral neck nodes I-III mandatory

Hard Palate

• Lateral fields + possible anterior field for midline lesions
• Submental node involvement risk requires lower anterior field

Lip

• Orthovoltage (100-250 kVp) or electrons for early T1/T2 lip lesions
• Lead shield placed behind lip to protect underlying teeth and mandible
• External beam for regional nodes if involved

7. Organ at Risk (OAR) Constraints - Conventional RT

8. Classical Phase Sequence Summary

Phase 1 (0 → 40 Gy):
  Large parallel-opposed lateral fields
  Primary + bilateral upper neck (levels I-III/IV)
  + Anterior lower neck/supraclavicular field (with midline block)

Phase 2 (40 → 50 Gy):
  Reduced lateral fields (off-cord posteriorly)
  + Posterior electron strips for posterior nodes
  + Anterior lower neck field continued

Phase 3 (50 → 60-66+ Gy):
  Boost field: GTV + 1-1.5 cm margin only
  OR interstitial brachytherapy boost (Ir-192)

9. Conventional vs Modern Techniques

10. Indications for Postoperative RT (PORT) - At a Glance