What are intra‑operative radiation therapy (IORT) machines, their common types, typical indications and ideal patient selection criteria, and the standard dose prescriptions for electron‑based and low‑energy X‑ray systems?

Intraoperative Radiation Therapy (IORT) Machines

Overview and Definition

IORT machines deliver a single, highly focused radiation dose directly to the tumor bed during open surgical procedures, allowing manual displacement of normal tissues and precise targeting of at-risk areas. 1

IORT represents a specialized radiation technique that fundamentally differs from conventional external beam radiotherapy by delivering treatment intraoperatively when the surgical field is exposed, enabling direct visualization and optimal normal tissue protection. 2, 3

Common Types of IORT Systems

Electron Beam Systems (IOERT)

• Electron-based IORT uses megavoltage electrons directed through specially designed applicators of variable sizes matched to the surgically defined region at risk. 1, 4
• These systems utilize pre-formed applicators that constrain both the area and depth of radiation exposure to avoid surrounding normal structures. 1
• Mobile self-shielded linear accelerators have eliminated logistical barriers by removing the need for patient transport during surgery or dedicated shielded operating rooms. 3

Low-Energy X-ray Systems

• Low-kV X-ray devices represent an alternative IORT delivery method with distinct dosimetric characteristics compared to electron systems. 3
• These systems offer portability advantages and different depth-dose distributions suitable for specific clinical scenarios. 3

High-Dose-Rate Brachytherapy

• HDR-IORT uses gamma-emitting radioisotopes to deliver intraoperative radiation as an alternative to electron beam approaches. 2
• This technique can be delivered through catheters placed during surgery for immediate or fractionated HDR delivery. 1

Primary Clinical Indications

Recurrent Disease in Previously Irradiated Fields

• IORT is particularly valuable for recurrent cervical cancer, rectal cancer, and gynecological malignancies within previously radiated volumes where additional external beam therapy would exceed normal tissue tolerance. 1, 5, 3
• This represents the most compelling indication, as IORT allows re-treatment when conventional approaches are contraindicated. 1, 5

Retroperitoneal and Soft Tissue Sarcomas

• For retroperitoneal sarcomas, IORT (10.0–12.5 Gy for microscopic residual disease; 15 Gy for gross residual disease) can be delivered immediately after resection to areas at risk while avoiding uninvolved organs. 1
• NCCN guidelines recommend surgery with or without IORT as primary treatment for resectable retroperitoneal disease. 1
• In retroperitoneal sarcoma series, 5-year local control rates reached 74% for primary tumors and 54% for recurrent tumors with IORT-based approaches. 1

Postoperative Boost in Soft Tissue Sarcomas

• After preoperative external beam RT (50 Gy), IORT can serve as a boost for positive margins instead of additional external beam doses. 1
• For postoperative settings without preoperative RT, IORT (10 Gy) followed by external beam RT represents an alternative approach. 1

Malignant Pleural Mesothelioma

• Experienced centers have used brachytherapy or intraoperative external beam radiation combined with extrapleural pneumonectomy for patients with residual tumors. 1

Ideal Patient Selection Criteria

Anatomic and Surgical Factors

• Patients must have surgically accessible tumor beds where normal tissues (bowel, viscera) can be manually displaced from the radiation field during the procedure. 1, 3
• The surgically defined region at risk must be amenable to applicator placement with appropriate size matching. 1, 4
• Surgical clips should be placed to identify high-risk areas, particularly for retroperitoneal or intra-abdominal sarcomas, to guide IORT targeting. 1

Disease-Specific Selection

• For retroperitoneal sarcomas: patients undergoing gross total resection with microscopic or gross residual disease at high-risk margins. 1
• For recurrent disease: tumors within previously irradiated volumes where cumulative external beam doses preclude additional conventional radiotherapy. 1, 5
• For cervical cancer: highly selected patients with recurrent disease in previously radiated fields or isolated unresectable residual disease. 1

Contraindications and Limitations

• IORT should not be used as routine alternative to external beam RT for primary treatment of intact cervical cancer. 5
• For early breast cancer, IORT shows higher ipsilateral recurrence rates compared to whole breast external beam RT, limiting its role as sole definitive treatment. 5, 6
• Patients requiring large-volume coverage are better served by fractionated external beam approaches. 5

Standard Dose Prescriptions

Electron-Based IORT Doses

• For microscopic residual disease: 10.0–12.5 Gy single fraction 1
• For gross residual disease: 15 Gy single fraction 1
• For postoperative boost (without preoperative RT): 10 Gy IORT followed by external beam RT 1
• For mesothelioma with residual tumors: doses integrated with brachytherapy or external beam techniques (specific doses vary by protocol). 1

Low-Energy X-ray Systems

• Dose prescriptions for low-kV systems vary based on tumor type and clinical scenario, with different radiobiological considerations compared to electron systems. 3
• For early breast cancer (where used): typically 20-21 Gy prescribed to tumor bed, though this shows higher recurrence than whole breast RT. 6, 3

HDR Brachytherapy IORT

• HDR-IORT doses are delivered through catheters placed intraoperatively, with fractionation schemes adapted to the clinical scenario. 2
• Specific dose prescriptions depend on whether used as monotherapy or combined with external beam RT. 2

Critical Technical Considerations

Dosimetric Requirements

• Comprehensive dosimetry documentation is essential, including beam characteristics for different applicator systems, doses to surrounding normal tissues, and quality assurance procedures. 4
• The planning target volume must account for the precisely defined surgical bed with direct visualization advantages. 4, 3

Multidisciplinary Coordination

• IORT requires coordinated interaction between surgical oncology, radiation oncology, and medical physics teams without causing undue additional toxicity. 2, 3
• Specialized equipment, trained personnel, and institutional expertise are prerequisites for safe IORT delivery. 3

Important Clinical Pitfalls

Single-Fraction Radiobiology Limitations

• Single-fraction IORT may be less favorable for certain tumor types compared to fractionated approaches due to different radiobiological effects. 5, 3
• The therapeutic ratio differs from conventional fractionation, requiring careful patient selection. 3

Limited Treatment Volume

• IORT treats only the surgically defined high-risk area and cannot address microscopic disease in adjacent regions requiring elective coverage. 5, 3
• This limitation makes IORT unsuitable as sole treatment for tumors requiring large-volume irradiation. 5

Not a Substitute for Adequate Surgery

• IORT is not a substitute for definitive surgical resection with oncologically appropriate margins; re-resection should be pursued when feasible before considering IORT. 1

Wound Healing Considerations

• When IORT is combined with external beam RT, adequate healing time must be ensured, with postoperative RT preferably initiated within 6-8 weeks to optimize outcomes. 5, 7