Radiotherapy for Rectal Cancer. Kevin Palumbo Adelaide Radiotherapy Centre

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1 Radiotherapy for Rectal Cancer Kevin Palumbo Adelaide Radiotherapy Centre

2 Overview CRC are common (3 rd commonest cancer) rectal Ca approx 25-30% of all CRC. Presentation PR bleeding: beware attributing to haemorrhoids even if present Altered bowel habit, tenesmus Anaemia LOW Persistent non-specific pelvic symptoms Screening over 50s Familial

3 Overview Phyical exam incl DRE, CBE, chemistry, +/- iron studies if anaemic. Referral to CR Surgeon or GE for colonoscopy or sigmoidoscopy and possible biopsy. If confirmed, CT chest, abdo, pelvis and MRI pelvis. PET scan, MRI or US liver in selected situations. If initial referral was to GE, the patient should then be referred to a specialist CR surgeon or general surgeon with CR experience.

4 Multidisciplinary Meeting Optimally all newly diagnosed cases should be discussed at a specific CR MDM CR Surgeon Radiologist Pathologist Rad Onc Med Onc If possible Hepatobiliary surgeon Pall Care Physician or nurse Stomal Rx nurse.

5 Background of XRT in Rectal Cancer With higher stage tumours there is a high local recurrence rate with conventional surgery alone. Rectum is mostly extra-peritoneal Contained loco-regional spread cf prox colon. Since the mid 70s radiotherapy has been trialled as an adjuvant either before or after Sx.

6 What we are trying to avoid

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11 Nodal Involvement by T Stage T1 6% T2 20% T3 65% T4 75%

12 Prognostic Factors T Stage Within T stage, proximity to CRM/location N Stage Distant metastases Vascular invasion

13 T2

14 T3 Non-threatened margin

15 T3 Involved margin

16 T4

17 T4

18 N+

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21 Pre-op XRT Advantages Better tolerated Lower dose usually sufficient due to less hypoxia Possible sphincter sparing Irradiated rectum mostly removed. Disadvantages Potentially over-treated early tumours in pre-mri era. Increased surgical morbidity

22 Post-op XRT Advantages Select patients most likely to benefit (T3 or N+). Less surgical morbidity. Disadvantages Not as well tolerated as pre-op with increased acute and late toxicity. Higher dose required due to surgical hypoxia

23 Pre-op XRT Alone Multiple trials in 70s and 80s Various fractionation regimens, Gy per fraction and 2-30# used. Poor pre-treatment staging and radiotherapy techniques. Over treated early cases and questionable tumour coverage and XRT dose distribution (coverage/tox). Most showed some improvement in LR but not OS.

24 Short Course Pre-op XRT 5 fractions of 5Gy over 1 week, early Sx. Convenience and reduced cost. Increased bowel, neurological and bone toxicity in some trials may be due to poor planning/technique. Swedish Rectal Cancer Trial Sx vs 25Gy in 5# followed by Sx within 1/52 T1-3 LR 11 vs 27% but increased further over time. 5yr OS 58 vs 48%

25 Short Course Pre-op XRT Dutch trial Same design as Swedish trial but standardised surgery with Total Mesorectal Excision LR 2.4% vs 8% No survival benefit Most effective for tumours <5cm from anal verge. No benefit if >10cm from anal verge.

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27 Pre-op XRT Individually most XRT alone trials showed reduction in LR rates with no or modest OS improvement. Meta-analysis of pre-op XRT (Camma etal, 2000) showed small OS benefit cf Sx alone.

28 Pre-op XRT plus Chemotherapy 45-54Gy in fractions over 5-6 weeks together with infusional 5FU followed by surgery 4-10 weeks later Allows tumour regression cf short course with early Sx. Esp if threatened or involved circumferential resection margin. Possibility of aiding sphincter sparing with lower tumours.

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30 XRT plus Chemotherapy Post-op chemo-rt (US approach) reduced LR and improved OS but significant toxicity concerns. Pre-op chemo-rt (European approach) also improved LR and OS but over treated early tumours in pre-mri era. Recurrence in T1/2, N0 is low with Sx alone therefore adjuvant Rx unnecessary ie limit to T3/4 or N+.

31 XRT vs Chemo-RT Trials of adjuvant XRT alone vs CRT showed the latter was superior for both LC and OS.

32 Pre-op vs Post-op CRT RCT of Pre-op vs Post-op CRT in Germany (Sauer et al NEJM, 2004) 823 pts, T3-4, N0 or Tany, N+ Long course, 1.80Gy, 28Fr to 50.40Gy, delayed surgery in preop group. 5 Yr OS 76% vs 74% p=0.8 5Yr LR 6% vs 13% p=0.006 Gr 3 or 4 acute tox 27% vs 40% p=0.001 Long term toxicity 14% vs 24% p=0.01 Pre-op superior with improved LC, less acute and late toxicity but no OS benefit. Improved sphincter sparing in those where the surgeon considered APR necessary before CRT, p=0.04.

33 Short Course RT Alone vs Long Course CRT TTROG Trial (Australia) 25 in 5 with early TME vs Long course CRT and delayed Sx. Both received post-op adjuvant chemo. MRI or US staged T3,N0-2, M0 3 Yr LR 7.5% for short-course group 4.4% for the long-course group (P=.24) 5 Yr OS 74% for the short-course group 70% for the long-course group (P=.62). Criticised for small numbers, low power and short follow up. Use short vs long selectively.

34 Future Trials Long course pre-op XRT alone Delaying Sx after short course RT. Short course followed by chemo then Sx. Some revisiting older protocols but now with improvements in imaging with MRI, surgery with Total Mesorectal Excision and improved CT planned XRT.

35 CRT as Definitive Treatment Clinical and subsequent pathological CR often seen after long course CRT. Also if medically unfit or refuse Sx. Trials now randomising patients with clinical and Bx CR to Sx vs observation.

36 Radiotherapy Treatment Planning Accurate staging Colonoscopy and MRI Distance from anal verge, length, location of nodes CT Simulation (Planning CT) Allows targeting of an internal target using both external and internal landmarks. Supine, full bladder Accurate alignment/levelling using room lasers Anal marker for very low tumours

37 Treatment Planning Targeting Primary tumour Nodal groups Meso and para-rectal Internal iliac/pre-sacral External iliac and superficial inquinal in selected cases or if involving anal canal. Critical structures Small bowel, bladder, hip joints/bone

38 Treatment Planning 3D Conformal vs IMRT Conformal Conventional, forward planned Regular volumes, eg cube. Simple, quick to deliver Relatively simple QA Less able to spare nearby organs at risk

39 Treatment Planning IMRT (Intensity Modulated RadioTherapy) Inverse Planning Able to create concave treatment volumes thus sparing OAR resulting in less side-effects. Requires much greater time to target, computing power, longer time to deliver. Greater possibilities of error and therefore more complex QA including daily set-up imaging.

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43 XRT Side-Effects Acute Fatigue LOA (Nausea rare even with chemo) Proctitis Enteritis Cystitis cutaneous desquamation (stomatitis from chemo) Management Diet Antidiarrhoeal Urinary alkalinisers Skin/mouth care Anti-emetics rarely required Treatment breaks rarely required.

44 Side-Effects Late Enteritis Proctitis Delayed surgical healing. Neurological Bone

45 Palliative XRT Local Disease High dose, long course (20-25#) +/- chemotherapy Short, hypofractionated (5-10#) Metastatic Disease?extensive or limited Bone, complicated and uncomplicated. Lung Brain, solitary vs multiple Nodal Hepatic