2. • Intraoperative radiotherapy (IORT) is the delivery of a single large radiation
dose to the tumor bed during surgical resection.
• It involves the delivery of radiation during surgery using various types of
radiation sources/technologies, including IOERT, HDR-IORT and
electronic brachytherapy/low-kilovoltage x-rays (KV-IORT).
• IORT is used to treat cancers that are difficult to remove during surgery and
there is a concern that microscopic amounts of cancer may remain.
3. • IORT allows direct radiation to the target area while sparing normal surrounding
tissue.
• IORT allows higher effective doses of radiation to be used compared to
conventional radiation therapy.
• It's not always possible to use very high doses during conventional radiation
therapy, since sensitive organs could be nearby.
• IORT also allows temporarily move nearby organs or shield them from radiation
exposure.
• Effective use of IORT requires a multidisciplinary approach, including close
cooperation with surgical oncology and medical physics.
4. HISTORY
• The initial clinical use of IORT dates back to the early 1900s, when IORT was
performed using soft X-rays and moving patients from the operating room to the
radiotherapy bunker.
• The first IORT using electron beams (IOERT) was carried out in November 1976
at Howard University, in a bunker equipped with an operating room.
• In the 1980s, in order to combine technical advantages of brachytherapy with
logistic advantages of IORT, high dose rate IORT (HDR-IORT) was implemented
at Memorial Sloan-Kettering Cancer Center, using a portable HDR machine .
5. • Since the 1990s dedicated linear accelerators have been created to
solve IORT logistical problems.
• In 1998, a new professional society, the International Society of IORT
(ISIORT) was created for the scientific and clinical development of
IORT.
• The ISIORT has now over 1000 members from more than 20 countries
and a scientific meeting is organized every two years. The first ISIORT
meeting was held in September 1998 in Pamplona, at the University of
Navarre, one of the most famous IORT centers.
6. There are three principal models used in clinical practice :
• Mobetron, from“Intraop Medical Incorporated”, California USA,
• Novac7 , from “New Radiant Technology”, Italy and
• Liac from “Sordina”, Italy.
These machines are small linear accelerators producing electron beams
which can be positioned directly in the existing operating rooms, with
no special shielding required
• Intrabeam Photon Radiosurgery System (Zeiss Inc, Germany) is used
for breast cancer treatment : it is a miniature electron beam-driven X-
ray source that provides a point source of low-energy X-ray (50 kV
maximum) at the tip of a 3.2 mm diameter tube.
7.
8.
9. • The LIAC 12, LIAC 10 and NOVAC 11 accelerators, created by Sordina IORT
Technologies, are the state of the art in this innovative therapy, developed to
respond to the patient’s mental, physical and logistical needs.
10.
11.
12.
13.
14.
15. • IORT team should be:
1. The surgeon
2. The radiation oncologist
3. The radiation physicist
4. The radiotherapy technologist
5. The anesthesiologist
6. The nursing staff
16. • The surgeon discusses clinical cases and the best surgical procedure
with radiation oncologist and co-operates in setting up the patient
during IORT
• The radiation oncologist is clinically responsible for prescription and
delivery of treatment and decides on IORT dose, field size, beam
energy and technical approach according to disease extension and the
closeness to organs at risk.
• The radiation physicist is responsible for dosimeter data acquisition
and for machine quality control.
• It is important that radiation physicists have dosimeters data readily
available to calculate the monitor units required to deliver an adequate
dose prescription.
17. • The radiotherapy technologist is the professional profile dedicated to
the mobilization of the IORT accelerator during docking procedure and
to deliver the dose prescribed by the radiation oncologist.
• Radiotherapy technologist is responsible for irradiation data
registration and co-operates for quality assurance treatment.
• The anesthesiologist must control the patient’s vital signs during
irradiation through a remote system or by closed-circuit television;
rapid access into treatment room is required to attend to patient in any
instance.
18.
19.
20. Dose specifications
• Traditionally, IORT procedures performed under the RTOG protocol have
specified that the 90% isodose line covers the target volume, whereas the ICRU
Report 3559 recommends that the dose be prescribed at dmax.
• Therefore, TG-48 recommended that both the 90% dose and the maximum dose
should be reported.
• This Task Group recommends that the dose be prescribed at the 90% isodose
level and then the dose be reported at both the 90% level and dmax.
• However most IORT groups follow the convention of prescribing to the 90%
isodose level to ensure coverage of the target by the 90% isodose line.
21.
22. Treatment delivery Parameters
• The decision-making process will include consideration of intraoperative information
by the pathologist concerning resection margins, tumor infiltration into surrounding
tissues, histology, and other considerations such as risks to neighboring tissues and
critical structures.
• For some tumors, additional surgical preparation may be necessary to render the target
accessible to electron irradiation (e.g., the preparation of a flat target area for IORT for
breast cancers).
• Definition of target depth and lateral extensions of the tumor and selection of beam
energy will depend mainly on these criteria.
• Intraoperative sonography to measure target depth or the distance of risk organs from
the target has been suggested.
• Beam energy is usually selected to place the 90% isodose line of the dose distribution
of the chosen applicator at the distal depth of the target
23.
24.
25.
26.
27.
28.
29. Benefits of IORT
• Saves time: The entire therapeutic dose of radiation is given
immediately at the time of surgery while the patient is still under
anesthesia. This allows the patient to complete the therapy
sooner, allowing the patient to return to normal life more quickly.
• Convenience for patients: Traditionally, patients would need to
come back to undergo radiation therapy for five days a week for
up to three to six weeks after they heal from surgery. For most
patients who undergo IORT, there are typically no return trips for
radiation.
• Targeted radiation therapy: Radiation is given directly and
internally to the sections of the sites with the biggest risks of
cancer reoccurrence.
• Team approach: The Radiation Oncologist is in the operating
room with the surgeon.
• Decreased side effects: IORT has been found to decrease side
effects such as red rashes and skin irritations when compared to
traditional radiation therapy.
31. Recurrent Rectal Cancer
• Isolated recurrences limited to the pelvis are the most frequent problem
after resection of locally advanced rectal carcinomas.
• IORT can be considered an ideal “boost” technique in order to obtain
dose-escalation ; EBRT in combination with IORT, in fact, allows local
delivery of a tumoricidal biological dose.
• The target volume is the “higher risk area” (i.e. where the tumor is
fixed or where there is a macroscopic or possible microscopic
residual).
32. • In locally advanced rectal cancer as well as in recurrent rectal cancer,
most studies referred an IORT median dose of 15 Gy (range 12.5–20
Gy) specified on 90% isodose .
• The most frequent complications are urinary infections and
symptomatic or objective neuropathy ; the ureter is not a dose-limiting
structure but, as ureteral narrowing or obstruction can occur, stent
positioning before surgery is suggested.
• Peripheral nerves are the main dose-limiting structures for IORT but
significantly fewer complications occur for doses of 12.5 Gy or less .
33.
34.
35. Retroperitoneal soft tissue sarcomas
• Surgery is the main treatment and provides the most favorable
prognosis after complete resection (R0) but complete surgical resection
is often difficult or impossible due to the anatomical location of these
tumors and the frequent invasion of contiguous retroperitoneal
structures .
• In this scenario, IORT appears to be an appropriate treatment,
associated with EBRT, with the aim of improving local control.
36.
37. • IORT can be delivered prior to as well as after EBRT and the median
dose is 15 Gy with a range of 10-20 Gy ; the target is the tumor bed
with a 1-3 cm safety margin and the dose is generally prescribed on
the 90% isodose.
• Potential side effects of intra-operative treatment are related to the site
of the target volume.
• Neurotoxicity is the most common side effect , particularly when the
IORT dose is higher than 15 Gy.
• Retroperitoneal abscess incidence is low while ureteral stricture may
occur when ureter is included in irradiation field .
38. Breast cancers
• The idea of a single-shot treatment by IOERT, as proposed by the
Milan Group, is tempting especially in low risk patients, but follow-up
periods far beyond 5 years are mandatory to provide definitive
evidence on long-term local control rates .
• An interesting multicentre trial of Targeted Intraoperative Radiation
Therapy (TARGIT) had as principal objective to determine whether
IORT targeted to tumor bed could provide equivalent local control
compared with whole-breast irradiation in patients with early-stage
invasive breast cancer .
39. Technique
• IORT technique in breast cancer
procedure:
• After lumpectomy with satisfactory
tumor-free margins dedicated
aluminium-lead disks are placed above
the pectoralis muscle in order to
minimize irradiation to thoracic wall.
• Then mammary parenchyma is sutured
in surgery breach area and target volume
thickness is measured.
• Finally an applicator of proper diameter
is placed in tumor bed and sterile gauze
are positioned between skin and
applicator’s edge.
• Optimal energy is selected on the basis
of measured target thickness.
• Dose varies according to treatment
“rationale” (single shot versus boost)
and is prescribed on 90% isodose
40.
41. Targeted intraoperative radiotherapy versus whole
breast
radiotherapy for breast cancer (TARGIT-A trial): an
international, prospective, randomised, non-inferiority
phase 3 trial
Jayant S Vaidya et al
42.
43. Findings
• 1113 patients were randomly allocated to targeted intraoperative
radiotherapy and 1119 were allocated to external beam
radiotherapy.
• Of 996 patients who received the allocated treatment in the
targeted IORT group, 854 (86%) received targeted IORT only and
142 (14%) received targeted IORT plus EBRT.
• 1025 (92%) patients in the external beam radiotherapy group
received the allocated treatment.
• At 4 years, there were six local recurrences in the intraoperative
radiotherapy group and five in the external beam radiotherapy
group.
• The Kaplan-Meier estimate of local recurrence in the conserved
breast at 4 years was 1·20% in the targeted IORT and 0·95% in
the EBRT group (difference between groups 0·25%, –1·04 to
1·54; p=0·41).
44. • The frequency of any complications and major toxicity was similar in
the two groups (for major toxicity, targeted intraoperative radiotherapy,
37 [3·3%] of 1113 vs external beam radiotherapy, 44 [3·9%] of 1119;
p=0·44).
• Radiotherapy toxicity (Radiation Therapy Oncology Group grade 3)
was lower in the targeted intraoperative radiotherapy group (six
patients [0·5%]) than in the external beam radiotherapy group (23
patients [2·1%]; p=0·002).
• Conclusions
For selected patients with early breast cancer, a single dose of
radiotherapy delivered at the time of surgery by use of targeted
intraoperative radiotherapy should be considered as an alternative to
external beam radiotherapy delivered over several weeks
45. • Another important IORT trial is the ELIOT trial conducted by Veronesi
and co-researchers .
• In this study, 590 patients affected by unifocal breast carcinoma up to
a diameter of 2.5 cm received wide resection of the breast followed by
IORT with electrons.
• 97% percent of the patients in this study had IORT as the sole
radiation treatment modality.
• After a follow-up from 4 to 57 months (mean 24 months, median 20),
19 patients 3.2%) developed breast fibrosis – mild in 18, severe in 1 –
which) resolved within 24 months.
• Local recurrences developed in three patients (0.5%), ipsilateral
carcinomas in other quadrants in three patients and contralateral breast
carcinoma in five.
• One patient (0.2%) died of distant metastases
46. Pancreatic cancers
• Prognosis for pancreatic cancer remains poor with a high incidence of local relapse,
even when disease is potentially resectable.
• In order to overcome this problem, several studies have been conducted with the
delivery of IORT to the tumor bed following pancreaticoduodenectomy, showing an
increase in local control without a prolongation of survival .
• Referred IORT doses are usually 10-15 Gy with a range from 10 to 30 Gy .
47. • The treatment field includes retroperitoneum and tumor bed while the
pancreatic remnant is usually excluded.
• The major retroperitoneal blood vessel, i.e. aorta, celiac axis, superior
mesenteric artery, superior mesenteric vein, portal vein and inferior
vena cava can be included in IORT field because they are not
particularly radiosensitive .
• The most frequent postoperative complications are anastomotic
leakage, peripancreatic abscess formation and pancreatic fistula.
• IORT is appreciated for the lasting effect in pain control in patients
with unresectable disease
48.
49. Vertebral metastasis
• Intraoperative radiotherapy (IORT) during kyphoplasty in order to
regain immediate stability, sterilize the metastasis and continue with
chemotherapy without a delay of several weeks.
