Radiotherapy What are our options and what is on the horizon. Dr Kevin So Specialist Radiation Oncologist Epworth Radiation Oncology

Transcription

1 Radiotherapy What are our options and what is on the horizon Dr Kevin So Specialist Radiation Oncologist Epworth Radiation Oncology

2 Outline Advances in radiotherapy technique Oligo - disease

3 Advancements in radiation technique 2D planning 3D conformal radiotherapy planning Multiple fields Static blocks (multi-leaf collimators - MLC) Intensity modulated radiotherapy (IMRT) Multiple fields Dynamic MLC Dose painting

4 What are the benefits of IMRT More conformal treatment ( wrapping of dose) Reduction is dose to adjacent organs/tissue Results in lower rates of toxicities Allows for: Dose escalation (sequential or simultaneous integrated boost - SIB) Considerations: Requires more careful treatment planning geographical miss Knowledge of natural history / spread Account for internal motion and uncertainties Utilisation of all available information/imaging

5

6

7

8

9

10 What are the benefits of IMRT - Toxicity Ng et al. Radiother Oncol 2016; 121(2):

11 Systematic review / meta-analysis quantifying the pcr rates with dose escalated pre-operative chemoradiotherapy treatment 18 studies met the inclusion criteria, 14 studies were included for the metaanalysis Pooled pcr rate was 20.4% Pooled grade 3 toxicity was 10.3%

12 Simultaneous integrated boost (SIB) Method of dose escalation that utilises dose painting ability of IMRT Whilst minimising the additional radiation dose to adjacent organ/tissue associated with sequential boost treatment Hypofractionated treatment (higher dose per fraction) radiobiological benefit Does not extend treatment duration Tey et al. J Cancer 2017; 8(16):

13 Lupattelli et al. Radiat Oncol 2017; 12: 139

14 What are our options for radiotherapy Locally advanced disease Neoadjuvant / adjuvant radiotherapy Metastatic disease Oligometastatic disease Widespread metastatic disease Oligoprogressive / oligorecurrent Synergistic - immunotherapy Palliation

15 What are our options for radiotherapy Locally advanced disease Neoadjuvant / adjuvant radiotherapy Metastatic disease Oligometastatic disease Widespread metastatic disease Oligoprogressive / oligorecurrent Synergistic - immunotherapy Palliation

16 Oligometastatic disease Extension of the spectrum theory, Hellman coined the term oligometastatic disease There existed a transitional state between localised and more widespread, disseminated metastatic disease Full metastatic growth ability has not been achieved Metastases are limited in their number and location With further progression, tumour seeding efficiency increases Hellman S. and Weichselbaum R. JCO 1995; 13(1): 8-10

17 Oligo- disease Oligometastatic disease No consensus definition State of metastatic disease that is limited Number (often either up to three or five) Location Disease that is not rapidly spreading Other scenarios: Oligorecurrent Oligopersistant / Oligoprogressive Relies on the use of accurate diagnostic imaging techniques PET/CT MRI

18 Colorectal cancer Almost 50% of patients with colorectal cancer will develop metastatic disease Most common site is lung and liver One of the tumour types that often presents with solitary recurrence or oligometastatic disease Newer and more effective chemotherapeutic agents and molecular targeted therapies 1. Wang CC, Li J. World J Gastroenterol 2012;18: 25-33

19 Management National Comprehensive Cancer Network (NCCN) guidelines Recommends aggressive local treatment with radical surgical resection in resectable oligometastatic disease limited to the lung or liver Liver resection achieves 5yr OS ranging from 40 to 58% Pulmonary resection 5yr OS rates in the range of 38 to 50% However, not all patients are suitable candidates for surgical resection Technical factors Co-morbidities Ricardi et al. J Radiat Res 2016; 57(S1): i58-i68

20 Alternative non-surgical treatment options Stereotactic ablative / body radiotherapy (SABR / SBRT) Radiofrequency ablation (RFA) Irreversible electroporation (IRE) Cryotherapy Microwave ablation Invasive Location / access issues Uncorrectable coagulopathy Inability to undergo general anaesthesia

21 What is stereotactic radiosurgery/ radiotherapy Various terminology used Stereotactic body radiotherapy (SBRT) Stereotactic ablative body radiotherapy (SABR) Stereotactic radiosurgery = single fraction Stereotactic radiotherapy = multiple fractions Blurring of lines: Small volume High doses of radiation Small number of treatments (usually ranging from 1 to 5) Large dose per fraction Highly conformal / steep isodose fall off / sharp dose gradients

22 Planning requirements

23 How are the steep dose gradients achieved Multiple static beams (up to 10-12) delivered at various angles +/- intensity modulated radiotherapy (IMRT) Continuous arcs +/- volumetric modulated arc radiotherapy (VMAT)

24

25 Multi-leaf collimators Volumetric modulated arc therapy (VMAT)

26 Positioning / Motion management Positioning External immobilisation devices Cone-beam CT / ExacTrac Treatment couch 6 degrees freedom of movement Fiducial markers Respiratory motion management 4D-CT Respiratory gating Abdominal compression

27 External immobilisation Achieves and maintains correct patient positioning in a 3-D space Minimises patient and target lesion motion during treatment delivery

28 4D-CT

29 Respiratory gating

30 Abdominal compression

31 EVIDENCE

32 Wild et al. Visc Med 2017; 33: 54-61

33 Wild et al. Visc Med 2017; 33: 54-61

34 Conclusions Consider in: Patients who are not surgical candidates Combined modality treatment Criteria Complete intrahepatic tumour clearance cannot be achieved by surgery alone e.g. insufficient remnant No more than three liver metastases None larger than 6cm Contraindication: Child Pugh score > 7 Patient is unable to lie flat for 30 to 40 minutes Previous radiotherapy Dose constraints are unable to be met

35 Immunotherapy and radiotherapy Early trial results on PD1 and PD-L1 blockade have shown some early promising results in patients with microsatellite instability (MSI) Patients with MSI-high (MSI-H) tumours may represent a subgroup more likely to benefit from immune checkpoint inhibitors Radiation Causes immunogenic cell death of cancer cells cross priming of tumour specific T-cells Alters the microenvironment within the irradiated field Abscopal effect = phenomenon whereby an index lesion is irradiated and a response is seen at a distant metastatic site outside the radiation path Synergistic effects?? Radiotherapy alone rarely induces an effective anti-tumour immunity that would result in systemic tumour rejection

36 Unanswered questions Best combination? Timing? Dose? Fractionation?

37 Thank you