Intraoperative radiotherapy IORT in women with early low risk breast carcinoma' Preliminary results

1
Intraoperative radiotherapy (IORT) in women
with early low risk breast carcinoma.
Preliminary results and quality of life (QoL)
evaluation -phase II study-

• Maluta S, Marciai N, Gabbani M, Giri MG,
  Nadalini L, Tedeschi U, Genna M , Pioli F,
  Guariglia S, Meliadò G.
• Radiotherapy Dept, Health Physics Unit,
  Surgery Dept I, Surgery Dept II,
  Psychooncological Unit of University-Hospital
  of Verona, Italy

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Primary endpoint

• To demonstrate that a single fraction of
  radiotherapy given intraoperatively (IORT) and
  targeted to the tissues at risk of local
  recurrence gives an equivalent outcome to
  standard post-operative radiotherapy after breast
  conserving surgery
• In women affected by early breast cancer with
  factors predicting a low and local risk of
  recurrence (see selection criteria).

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Secondary endpoints

• Local relapse rate
• Event-free survival
• Overall survival
• Cosmetic outcome
• Local toxicities
• Quality of life
• Cost benefit analysis

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Pathological parametersacceptable
unacceptable

• Age gt50 year
• Post menopausal
• Tumor 20 mm
• Grade I-II
• Clear margins
• ER/PR
• Node negative
• Invasive ductal carcinoma

• Tumor gt 20 mm
• Margins not clear
• Grade gt II
• EIC
• Multifocal
• Lobular type
• Node positive

• If the patient is found to have acceptable
  pathology parameters no further radiotherapy is
  indicated and patient receive appropriate
  systemic management (TAM).

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Patients

• From July 2006 to Mars 2008, 141 patients
  suitable for breast conserving surgery were
  enrolled in a phase II study using IORT as
  radical adjuvant treatment after surgical
  resection
• A specific informed consent approved by Ethical
  Committee was required
• The inclusion/exclusion criteria were the
  following

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Selection criteriainclusion
exclusion

• age gt 50 years (postmenopausal status) ,
• pathologically documented invasive breast
  cancer,
• G1-2 grading,
• no previous breast irradiation,
• cT1N0M0 stage,
• unifocal tumor radiologically documented,
• good performance status,
• patient availability for follow-up
• informed consent.

• Age lt 50 years
• Not suitable for breast conserving surgery
• Multicentric breast cancer
• ECOG gt 2
• Recurrent breast cancer

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Informed consent

• Description of procedure
• Aim of treatment
• advantages in terms of
• - length of treatment,
• - control of disease,
• - less side effects in comparison with
  alternatif treatments
• Side effects
• Possibility of refusing in every moment the
  treatment

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Methods

• Patients were treated by
• wide local excision of primary tumor and
  axillary management, including sentinel node
  evaluation.
• IORT with a dedicated linear accelerator
  ( Mobetron), with an energy ranging between
  3-9 MeV , and a dose-rate from 2.5 to 15 Gy/min.
  

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Key Mobetron FeaturesTab.1
(However, in Verona the IORT-dedicated operating
room is radioprotected)
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Applicators
From 3 to 10 cm (with 5 mm increment) 15 with
angle 0 15 with angle 15 15 with angle
30 Total applicators n45
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MOBETRON - INTRAOP Intra-op Medical, Inc 3170
De la Cruz Blvd, Santa Clara CaliforniaTab.2
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Electrons 6 MeV

• Dose distribution direct beam

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Electrons 12 MeV

• Dose distribution - direct beam

at high energy a Plexiglas disk has to be
inserted in the applicator to compensate the
build up of electrons
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REPORT of American Association of Physicists in
Medicine (AAPM) Radiation Therapy Committee Task
Group N 72

• Intraoperative radiation therapy using mobile
  electron linear accelerators
• Med. Phys. 33 (5),
  MAY 2006

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ISTISAN - Rapport 03/1for QA in IORT

• Equipments
• Professional x-rad exposed people (physicien,
  phisicist, surgeon, nurse, technicien)
• Treatment procedures
• Dosimetry
• Radioprotection
• Quality control program
• Informed consent

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Quality assurance proceduresTab.3
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IORT dose

• A tumoricidal dose of 21 Gy, being biologically
  equivalent to 60 Gy external irradiation, was
  delivered to the 80 reference isodose with 2 cm
  margins laterally.
• Applicators, with diameters varying between 7 to
  3.5 cm, were directly inserted into the tumor
  bed.
• A round or ellittic Plexiglas disk was inserted
  in the applicator to compensate the build up of
  electron especially at high energy

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Planning of surgical procedure and IORT
previsional treatment planning

Tumor resection and gland reconstruction In some
cases the protection of the toracic wall is
achievel by using a plexiglas disk
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Radiological verification of free margins
We are preparing the PTV
Verification of treatment parameters and
treatment planning
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Applicator insertion
Connection with the operating bed
applicator
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collimator positioning and soft- docking
Dose delivery 21 Gy
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Systemic adjuvant chemotherapyTab.4. n64
patients evaluated
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Technical problems

• All patients underwent IORT without technical
  problems.
• In very few cases irradiation was briefly
  interrupted due to the movement of the thoracic
  wall caused by the patient breathing which
  modified the soft-docking alignment.
• No definitive treatment interruption occurred.

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Results

• Considering the brief follow up results were
  reported in terms of
• Local recurrence 1 (0.7)
• Distant metastases 0
• Acute and Late toxicity (tab. 5)
• Quality of Life (Tab.6)

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Feature of local recurrence(pts 49 year old,
recurrence in not irradiated area, 8 months after
IORT)

• multiple biopsy before IORT
• - Sup. Ext. dx
• - Tmic
• - G3 (exclusion criterium)
• Node negative
• (Diagnosis revised by IEO)

• Pathological specimen
• - Para-areolar sup
• - Tis
• G3
• EIC
• - ER negative
• PrR negative
• Ki 67 10
• HER-2 score 3

Unacceptable path.parameters
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In 7 pts a transient haematoma occurred after
IORT Of these one required a re-operation These
complications were reported as surgical
complications
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Quality of Life Tab.6

• In 49 patients QoL was evaluated by interview and
  SF 36 questionnaire (Italian version by Ware JE
  jr, Apolone G, Mosconi P).
• The elevated age of women and previous cancer
  disease affect negatively the physical activity
  and the mental condition. A elevated affective
  loss (43) is reported.

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Conclusions

• IORT starts adjuvant therapy at the time of
  surgery when residual tumor cells are most active
• IORT in breast cancer is feasible and safe as it
  allows an accurate estimation of tumor bed (no
  geometric miss).
• IORT allows immediate administration of
  chemo-ormonal therapy, solving the problem of
  sequencing therapy
• IORT reduces the dose to controlateral breast

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Conclusions

• The dose of 21 Gy might safely be delivered even
  if the time of operation was prolonged by approx
  20 minutes.
• IORT offered the advantage of a very short
  radiation time,it increased the possibility of
  sparing normal tissues, and achieved elevated
  values of QoL, reducing the acute and late side
  effects in comparison with conventional
  irradiation.
• In spite of these promising early results it
  shouldnt be forgotten that a longer follow up is
  necessary to demonstrate whether a large single
  dose of radiotherapy may achieve a sufficient
  local control without severe late effects.
• Until now the local control has to be considered
  sufficient, provided that exclusion criteria and
  unacceptable pathological parameters be carefully
  evaluated.

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Greater patient convenience -Shorter overall
treatment time-More cost-effective
More time for private life and less
hospitalization
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IORT in Verona has been carried out thanks to
Cariverona Foundation

• Radiotherapy Dept
• N. Marciai, M. Gabbani
• Physics Health
• G. Chierego, MG. Giri, S. Guariglia, G. Meliadò
• Surgery I - II
• U.Tedeschi, M.Genna