Impact of imaging on newer radiation techniques in Gynaecological cancer

Morphology of local tumour (MRI) Mapping of metastatic disease (PET/CT) Tailored EBRT (IMRT, selective dose escalation) Conformal brachytherapy (reduced toxicity, ? Improved control & survival?) Newer insight into clinical behaviour of cancer

FIGO Staging of cervix cancer Five year survival from around the world Stage-1Stage-2Stage-3Stage %38-68% 22-61% 0-10%

Cervix, 6 cm 2b Examination under anaesthesia Axial MRI 02/11/02663

Histology EUA MRI

41 year old FIGO IIIB Extensive infiltration lower uterine segment Exophytic component in vaginal lumen Infiltrating beyond the vagina on left Mass 5.7 x 4.8 x 6.2 cm Left parametrial extension L external iliac node

40 Gy Whole Pelvis Ant & Post R&L lateral fields Prone on Bellyboard Ant-Post R&L Lat fields 10 Gy boost to Left ext iliac node 10 Gy boost LPSW

40 Gy + cisplat (+10 Gy LN boost) Bulk of tumour resolved Residual tumour left cervix and upper vagina Extension into left parametrium

Tandem inserted using real time Ultrasound guidance MRI taken one hour after insertion and treatment Patient moved from brachy theatre to MRI scanner

Dose escalation Radiation resistance Infiltrating disease Presence of metastases

In conformal brachytherapy where dose is limited to residual tumour, the incident dose at point A is variable. In patients treated with LDR the dose (80 Gy) was prescribed to Point A. This meant that patients who responded well to EBRT had small residual with diameter of <4cm. All such tumours would have received much higher than the prescribed 80 Gy and hence had unintended dose escalation!

Mobilization of Viable Tumour Cells into the Circulation During Radiation Therapy. Martin et al 2013, Red journal /j.ijrobp

A randomised, two-by-two factorial phase 3 study. Stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): (Bradley et al. 2015). Standard-dose versus high-dose conformal radiotherapy high-dose (74 Gy in 37 fractions) or standard dose (60 Gy in 30 fractions) radiotherapy concurrently with weekly paclitaxel and carboplatin with or without cetuximab, followed by consolidation chemotherapy in all groups.

Interpretation of results were: 74 Gy with concurrent chemotherapy not better than 60 Gy plus concurrent chemotherapy Addition of cetuximab to concurrent chemoradiation and consolidation treatment provided no benefit in OS Median overall survival was 28·7 months for 60 Gy And 20·3 months (17·7–25·0) for 74 Gy

The authors of RTOG 0617 still believe the way forward is still the radiation dose intensification! RTOG 1106 is using a mid-treatment PET adapted hypofractionated radiation therapy boost to intensify radiation dose to residual tumour volumes during a total duration of 30 fractions (NCT ). RTOG 1308 is exploiting the protons compared with photons to escalate radiation dose to 70 Gy (NCT ). Both of these trial designs were built on the knowledge gained from RTOG 0617.

Questions…