What are the indications for IMRT, brachytherapy, intraoperative radiotherapy (IORT), extra-corporeal radiotherapy and particle therapy in the management of BSTTs?

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The standard adjuvant radiotherapy, whether used pre-operatively or post-operatively in the management of sarcomas tends to be 3-D Conformal Radiotherapy (3-DCRT). However, there are additional older (brachytherapy) and newer (IMRT, particle therapy etc) methods of delivering the radiation that may have advantages in specific situations.

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There is definite evidence that adjuvant brachytherapy improves local control over surgery alone in the management of high grade soft tissue sarcomas of the extremity and superficial trunk.[1][2] The enhancement of local control however does not extend to low grade tumours.[1][3][2] The addition of brachytherapy does not seem to increase morbidity significantly over surgery alone, though a higher wound complication rate is noted,[4] as with pre-operative radiation. Brachytherapy may have a higher early wound complication rate when compared with External Beam Radiation alone.[5]

Brachytherapy has been used as a “boost” in retroperitoneal sarcomas (RPS), intraoperatively, either with pre-operative[6] or post-operative[7] external beam radiation. An enhancement of local control has been suggested in several case series. A small randomised study showed benefit with use of HDR–IORT.[8] However no advantage with HDR–IORT is seen in local control or overall survival at 10 years when combined with preoperative radiotherapy. [9]

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Intra-operative radiotherapy (IORT)

IORT is used as a method to boost radiation doses to areas of subclinical and microscopic disease positivity identified during time of the surgery. The advantages are it allows high doses to be delivered to areas of clinical concern while sparing normal tissue. IORT can be delivered with an external beam method,[10] using electrons or with high dose rate brachytherapy (HDR).[7] A small randomised study of 35 patients compared post-operative external beam radiation alone in one arm with IORT boost followed by smaller doses of external radiation for patients with retroperitoneal sarcomas. Lower local recurrences (6 out of 15) were reported with IORT compared with post-operative external radiation alone (16 out of 20). Significantly lower radiation enteritis was noted in the IORT arm than the control arm; however a higher rate of neuropathy was reported.[8]

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Intensity modulated radiotherapy (IMRT)

IMRT or Intensity modulated radiotherapy is a radiation planning and delivery technique that is more complicated and potentially more precise than conventional methods of radiotherapy that use forward planned 3-D Conformal Radiation techniques.

IMRT has been evaluated to reduce wound complications by sparing the uninvolved tissues.[11] There are case reports of excellent local control and better sparing of normal tissue when used adjuvant with surgery[12][13][14][15] in limb and truncal sarcomas.

For retroperitoneal sarcomas there are a few plan comparison studies and case reports suggesting better dose conformity to the target and lower doses to organs at risk with IMRT technique.[16][17]

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Intraoperative extra-corporeal radiotherapy

Management of bone and soft tissue tumours (BSTTs) at times may involve resecting the diseased segment of the bone of a patient with bone or soft tissue tumour. The resected specimen can be replaced by an allograft or prosthesis. The use of Extracorporeal Radiotherapy to the bone fragment allows the patients own resected bone specimen to be use as an “autograft”.

The process involves “en bloc” wide excision of tumour, curettage and removal of tumour in theatre, than transportation of the specimen for Extracorporeal Radiation to a dose of 50Gy to 300Gy in a single fraction[18][19][20][21][22][23][24] and re-implantation in the patient, as an autograft.

There are a few case series around the world reporting generally good functional outcomes.[18][19][20][21][22][23][24] A higher complication rate, mainly infection and delayed healing is noted in some case series.[23]

Histopathological examination after Extracorporeal radiotherapy in one case series showed complete sterilization of tumour cells in all specimens examined, but viable chondrocytes capable of laying matrix.[20]

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Particle therapy

Standard radiotherapy utilises high energy X-Rays (gamma rays) or photon beams for treatment. Particle therapy is a form of external beam radiotherapy using beams of energetic protons, neutrons, or positive ions such as Carbon ions for cancer treatment. The most common type of particle therapy is proton therapy.

For protons and heavier ions, the dose increases while the particle penetrates the tissue and loses energy continuously. Hence the dose increases with increasing thickness up to the Bragg peak that occurs near the end of the particle's range. Beyond the Bragg peak, the dose drops to zero (for protons) or almost zero (for heavier ions). The perceived advantage of this energy deposition profile is that less energy is deposited into the healthy tissue surrounding the target tissue. There is no available confirmatory evidence comparing particle beam radiation with photon beam therapy (conventional radiation) in management of bone and soft tissue sarcomas. There are a number of published case series describing outcomes with proton beam[25][26][27][28] and carbon ion therapy[29][30][31][32] for bone and soft tissue tumours. A phase 2 study of patients with spinal and paraspinal sarcomas treated with particle beam therapy after biopsy or resection had a five-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively[33] Serizawa et al[31] from Chiba, Japan report on 24 patients with unresectable retroperitoneal sarcomas treated with Carbon ion therapy. The five year local for this group of unresectable patients is 69%, with no toxicity greater than grade 2. Scultz-Ertner[30] from Germany report 81% local control for Chordoma and 100% local control at three years for Chondrosarcoma in their experience. No grade 4/5 complications were noted.

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Evidence summary and recommendations


Evidence summary Level References
Brachytherapy improves local control over surgery alone in the management of high grade soft tissue sarcomas of the extremity and superficial trunk. II [1], [3]
Effect does not extend to low grade tumours. II [1], [3], [2]
Brachytherapy may have higher wound complication rate compared to External Beam Radiation. III-2 [5]
Brachytherapy boost with IORT may add small benefit over post operative external radiation alone for retroperitoneal sarcomas. II [8]
Brachytherapy boost with IORT adds no benefit to preoperative radiation alone for retroperitoneal sarcomas. III-2 [9]

Evidence-based recommendationQuestion mark transparent.png Grade
Brachytherapy (as an alternate or as a boost to external beam radiation) improves local control over surgery alone for high grade sarcomas for the limb and trunk.

Intraoperative radiotherapy (IORT)

Evidence summary Level References
IORT when combined with surgery and external beam radiotherapy may improve local control. II [8]
Other combinations and forms of delivering IORT, such as electron beam, may offer benefit. IV [7], [6], [10]
Evidence-based recommendationQuestion mark transparent.png Grade
IORT boost to external radiation could be considered in combination with surgery for management of retroperitoneal sarcomas.

Intensity modulated radiation therapy (IMRT)

Evidence summary Level References
Insufficient evidence to confirm IMRT results in lesser complications by more normal tissue sparing. Better conformity in plans and lower doses to normal tissues noted for both limb and retroperitoneal sarcoma plans. III-2, IV [11], [12], [14], [15]
Evidence-based recommendationQuestion mark transparent.png Grade
It maybe reasonable to consider IMRT for patients with retroperitoneal and extremity/truncal sarcomas as adjuvant to surgery, if resource permits, for potential advantages in reduction of radiation dose to normal tissues.

Intraoperative extra-corporeal radiotherapy

Evidence summary Level References
Case series from few centres around the world suggests en Bloc wide local excision, removal of tumour and reimplant of the “autograft” after a single large fraction of radiation to the resected fragment of bone is a viable option for reconstruction with satisfactory to good functional outcomes.

Doses of radiation used are 50Gy to 300Gy.

There appears to be complete sterilization of tumour at these dose levels.

IV [18], [19], [20], [21], [22], [23], [24]
Evidence-based recommendationQuestion mark transparent.png Grade
Reconstruction using the patients own resected bone (previously bearing the sarcoma) fragment after a large extra-corporeal dose of radiation is a possible option reported to have satisfactory to good functional outcomes.

Particle therapy

Evidence summary Level References
Particle beam therapy such as proton and carbon ion therapy appear to provide excellent local control in unresectable and partially resected sarcomas, particularly Chordomas, Chondrosarcomas of sacrum and skull base and retroperitoneal sarcomas. Toxicity reported appears to be low.

No direct comparison between particle beam therapy and equivalent doses of photon beam therapy exists for sarcomas.

IV [25], [26], [33], [29], [30], [31], [32], [28]
Evidence-based recommendationQuestion mark transparent.png Grade
Particle beam therapy appears to offer good local control with acceptable toxicity.

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Issues requiring more clinical research study

A number of gaps in the evidence have been identified. These include:


• Consensus / Confirmation that radiotherapy improves local control in Retroperitoneal Sarcomas.

• If above consensus/confirmation is reached, value of IORT as an additional boost to EBRT to further improve local control can be tested.


• Comparative study of 3DCRT and IMRT for Retroperitoneal and Limb/Truncal Sarcomas to demonstrate lower normal tissue toxicity with IMRT.

Intraoperative extra-corporeal radiotherapy

• Comparative study to determine function outcome differences between use of prosthesis, bone bank allografts and extra-corporeally radiated autografts.

Particle therapy

• Study comparing particle beam therapy and photon therapy for sarcomas with local control and toxicity as end points.

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  1. 1.0 1.1 1.2 1.3 Harrison LB, Franzese F, Gaynor JJ, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in the management of completely resected soft tissue sarcomas of the extremity and superficial trunk. Int J Radiat Oncol Biol Phys 1993 Sep 30;27(2):259-65 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8407399.
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Further resources