1. Opportunity for palliative care Research
Role of Radiotherapy in Multidisciplinary Management of Rectal Cancers
Dr Sushmita Pathy
Associate Professor
Department of Radiation Oncology
Dr BRA Institute Rotary Cancer Hospital
All India Institute Of Medical Sciences
New Delhi INDIA
Dr. Sushmita Pathy
Additional Professor
Department Of Radiation Oncology
Institute Rotary Cancer Hospital
All India Institute Of Medical Sciences
New Delhi INDIA.

2. Burden of Rectal cancer
Colorectal cancer third most common cancer worldwide.
More than 50% of the cases occur in more developed regions.
Highest Australia/New Zealand (ASR 44.8 & 32.2) lowest in Western Africa.
Mortality High in the less developed regions
India Highest in Mizoram (ASR - 4.5/Lakh population) Lowest in Dindigul, AP cancer registry (ASR – 1.4/Lakh population)
Globocan 2012& CI5 vol X

3. Need of Multidisciplinary Approach
Surgery is the gold standard
Proven benefits of total mesorectal excision
Parallel to improvement in surgical technique adjuvant therapy reduce local recurrence rate
Dramatic changes in management of rectal cancers.
Multidisciplinary management: Paradigm shift

4. Adjuvant Therapy: Rectal Cancer
High rate of local recurrence locally advanced disease. Tumor fixation is a limitation
Adjuvant radiotherapy preop/post op significant increase in loco-regional control
Sphincter sparing procedure . Organ preservation
No improvement with DFS,OS and distant metastasis
Role of adjuvant chemo-radiotherapy was evaluated to improve treatment outcome .

5. Adjuvant Therapy Description GITSG (1988)
4 arm trial S/S+RT/S+CT/S+CRT
227 patients B2 ,C(R0 resection)
10 yr OS 45 % vs 27%,LRR 10% vs 25%
Significant benefit with CRT
NSABP R-01(1988)
3 arm RCT
500 patientsPT3/T4N+
S/S+CT/S+RT
S+CT: Improved DFS& OS
S+RT: Reduction in LRR 16% vs 25 % favouring RT No survival benefit

6. Preoperative vs Postoperative approach
Pre-operative RT
Tumour downstaging and improve resection,
Better tolerance
Higher biologically effective dose intact vascularity.
Evaluation of patients on basis of pathological features not possible
Post operative RT
Hypoxic post surgical bed Chemotherapy and RT less effective
Higher morbidity : small bowel,large treatment volume
Selectively treat patients with high risk histopath features

7. Short Course Preoperative Radiotherapy
Study
Swedish Rectal cancer Trial
Folkesson J et al JCO 2005
PreopRT vs sug alone
1168
25Gy/5Fr/5days→Sug
Med FU 13 years
OS 38% vs30%, p 0.008
LRR 9%vs 26% p 0.008
Dutch study CKVO 95-04
Willem VG et al Lancet oncol 2011
PreopRTvs TME alone
1861 patients
25Gy/5Fr/5days→TME
Med FU 10 years
OS 48%vs 49% p 0.86
LR 5% vs 11% p

8. Adverse effects Of Preoperative Radiotherapy
Study
Swedish rectal cancer trial : Long term follow –up Birgisson JCO 2005
Increase in risk for early admissions(6 months) in
irradiated patients RR1.64
Bowel frequency,
Incontinence,
Urgency
Over all quality of life rated good
Swedish rectal cancer trial : Late GI toxicity Birgisson Br J sug 2008
Increased RR 2.49of late small bowel obstruction ,(post op anast leakage)
Abdominal Pain RR 2.09

9. Long course Preoperative chemoradiation
Neoadjuvant CTRT :Standard of care
Tumour downstaging
Improved resection.
Increased sphincter preservation
Higher pCR/local control
German rectal cancer Trial :
Preop CRT vs Post op CRT
T3/4,N+
Reduction in local failure 6%vs 13%
Improvement in sph preservation ( p=0.004) favouring preop CRT .
Saur et al NEJM 2004

10. Preoperative chemoradiotherapy
Trial
No of Patients
Randomisation
Median F/U LR OS
Toxicity
GERMAN
cT3-4
cN+
823
Pre op CRT-405
Post op CRT-395
134 months
( mo)
10yr
7.1% Vs
10.1% P
59.6%
59.9%
P – 0.85 -
EORTC 22921
4arm study
1011
1.Pre op RT Sx+/- CT
2. Pre op CRTSx +/-CT
10.4 Yrs
( )
10yrs
22.4% vs 11.8% vs 14.5% vs
11.7%
P –0.0017
49%vs
50.7%vs
51.8%vs
48.4%
P – 0.91
No sign. toxicity
Sauer R et al. German CAO/ARO/AIO-94 JCO 2012
Bosset J et.al. EORTC Lancet Oncol

11. Long vs Short Course Chemoradiotherapy
Study
No of Patients
Randomisation
Median F/U
3 yr LRR
5 yr OS
Toxicity
late
Australian Intergroup trial 2012
326
T3 N0-2 M0
SC – 163
LC – 163
5.9yrs
7.5% Vs
4.4%
P – 0.24
74%
70%
P – 0.62
G 3-4
5.8 vs 8.2
P-0.53
Polish rectal cancer group 2006
312
SC:156
LC 156
48 mths
Higher pCR in CRT
67.2%
Vs 66.2%
10.1%
Vs 7.1%
Tumour downstaging/higher pCR/ LRR
No conclusive evidence of survival benefit/sph sparing

12. MULTIDISCIPLINARY MANAGEMENT : WHERE ARE WE GOING?
Benefits of RT/CRT Vs Burden
Identify the patients at low risk of local recurrence, and ideally may not benefit from neo-adjuvant therapy
Prognostic role of circumferential resection margin (CRM)
ESMO sub-categorize rectal tumours (favourable, intermediate ,high risk ) based on MRI finding
(Low risk ?? Benefit )

13. OPTIMAL TIMING PREOP RT/CRT AND SURGERY
Short course: 25Gy/5fractions/5 days
11days/3-4 weeks Improved pCR Oncological outcome ?
Acute radiation reaction subside after RT
Long Course(CRT): Gy/25 fractions/5 weeks
More pronounced tumor regression pCR with prolonged interval
Oncological outcome ? Data lacking
No reason to delay beyond 6-8 weeks
Glimelius Front oncol 2014

14. Positioning & immobilisation
Supine/prone
Pelvic thermoplastic mask
CECT simulation
Target volumes:
Primary tumour + clinically +ve nodes >1cm
Entire mesorectum
Lymphnodes
Dose:
Shortcourse:25Gy/5Fr/1wk
Long course 45Gy/25Fr/5wk
Postop adjuvant* : 50.4Gy/28Fr/5.5 wk
*high risk histopath ≥ pT3,N+,LVSI,Margin positivity

15. INNOVATIONS IN RADIATION THERAPY
Three dimensional RT standard of care
New advances RT minimize toxicity and maximize efficacy.
Intensity Modulated and Image guided RT anatomically sculpt dose delivery reduce CTV-PTV margin and irradiated volume of small bowel
Proton therapy reduces bone marrow exposure : Reduces hematological toxicity. Better tolerance to chemotherapy

16. Three dimensional conformal Radiotherapy
Preplanning and localization.
Computed tomography imaging for three dimensional planning.
Target and critical structure delineation Contouring of the target volume including gross tumour volume ,clinical target volume, planning target volume /OAR.
Beam and field designing
Dose calculation.
Plan optimization and evaluation.
Treatment documentation and set up verification.

17. Organs at risk (OAR) : Dose constraints
Small bowel
Bladder
Femoral head
No more than 180 cc above 35 Gy
No more than 100 cc above 40 Gy
No more than 65 cc above 45 Gy
No more than 40% volume > 40 Gy
No more than 15% volume > 45 Gy
No more than 25% volume > 45 Gy

18. 48 M with complaints of bleeding per rectum & pain lower abdomen CECT : irregular wall thickening of distal rectum and proximal anal canal . No significant prerectal LN Colonoscopy growth starting 4 cm from anal verge, upper extent 8 cm.
Pre op CTRT 45Gy/25#/ 5week with concurrent capecitabine

20. Plan evaluation : Dose volume histogram

21. Mid rectal cancer: planned for preoperative chemo radiotherapy with intensity modulated radiotherapy
Technique CRT vs IMRT
GI toxicity(Gr 2) 62% %
Diarrhoea % 23%
Enteritis % 10%(p=0.02)
No diff in pCR rates
Samuelian et al IJROBP 2012

22. IMRT Vs CRT
Samuelian JM et al IJROBP 2012

23. IMRT-IGRT- SIMULATANEOUS INTEGRATED BOOST
Preoperative IMRT-IGRT with simulataneous boost 46 Gy in daily fractions of 2 Gy. Horseshoe shaped distribution of the dose to spare the small bowel. Simultaneous integrated boost till 55.2 Gy is prescribed on the tumor.
Local recc <3%. Grade ≥2 diarrhoea 18%
Acute toxicity <1% and <10% late grade 3 toxicity
Sermeus et al World J Gastro 2014
De Ridder et al IJROBP 2007

24. PROTON THERAPY Bragg peak is the characteristic of proton beam
Spread out Bragg peak (SOBP) summation of multiple beam
Sharp dose fall off spares tissue surrounding target
No exit dose

25. COMPARISON PROTON/3DCRT/IMRT
Colaco et al J Gastrointest oncol 2014

26. COMPARISION PROTON/3DCRT/IMRT
Colaco et al J Gastrointest oncol 2014

27. RADIOTHERAPY IN PALLIATIVE SETTING
Symptom based management
Haemostatic Radiotherapy
Local palliative Radiotherapy
Bone metastasis
Cord compression
Brain metastasis

28. Conclusion
Multimodal treatment approach in rectal cancers result in a better outcome.
Preop RT /Postop CRT improves local control and survival over surgery alone for locally advanced tumors
Neoadjuvant CRT : Tumor down staging improved resection/ sph preservation /local control: Current standard of care No evidence of survival benefit . Optimal combination challenge.

29. Conclusion
Long term data from RCT assess late toxicity of short vs long course therapy.
Newer RT techniques provide improved dose delivery with sparing of OAR.
Selection of patients who will benefit from neoadjuvant therapy will influence future directions

30. Thank you