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 ID: 382842
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Slide1
Opportunity for palliative care Research
Dr Sushmita PathyAssociate ProfessorDepartment of Radiation OncologyDr BRA Institute Rotary Cancer HospitalAll India Institute Of Medical SciencesNew Delhi INDIA
Dr.
Sushmita
PathyAdditional ProfessorDepartment Of Radiation OncologyInstitute Rotary Cancer HospitalAll India Institute Of Medical SciencesNew Delhi INDIA.
Role of Radiotherapy in Multidisciplinary Management of Rectal CancersSlide2
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 XSlide3
Need of Multidisciplinary Approach
Surgery is the gold standardProven benefits of total
mesorectal excision
Parallel to improvement in surgical technique adjuvant therapy reduce local recurrence rateDramatic changes in management of rectal cancers.
Multidisciplinary management: Paradigm shiftSlide4
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 metastasisRole of adjuvant chemo-radiotherapy was evaluated to improve treatment outcome .Slide5
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 benefitSlide6
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 possiblePost operative RTHypoxic post surgical bed Chemotherapy and RT less effectiveHigher morbidity : small bowel,large treatment volume Selectively treat patients with high risk
histopath
featuresSlide7
Short Course Preoperative Radiotherapy
Study
Swedish Rectal cancer Trial
Folkesson
J et al JCO 2005PreopRT vs sug alone1168
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
0.0001 Slide8
Adverse effects Of Preoperative Radiotherapy
Study
Swedish rectal
cancer trial : Long term follow –up Birgisson
JCO 2005Increase in risk for early admissions(6 months) inirradiated patients RR1.64Bowel frequency,Incontinence,UrgencyOver all quality of life rated good
Swedish rectal
cancer trial : Late GI toxicity
Birgisson
Br J
sug
2008
Increased RR
2.49
of late small bowel obstruction ,(post op
anast
leakage)
Abdominal Pain RR 2.09Slide9
Long course Preoperative
chemoradiationNeoadjuvant CTRT :Standard of care
Tumour downstaging
Improved resection. Increased sphincter preservation
Higher pCR/local controlGerman 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
Slide10
Preoperative
chemoradiotherapy
Trial
No of PatientsRandomisation
Median F/ULROSToxicityGERMANcT3-4cN+823
Pre
op CRT-
405
Post op CRT-395
134 months
(90-184 mo)
10yr
7.1%
Vs
10.1%
P - 0.048
10yr
59.6%
Vs
59.9%
P
– 0.85
-EORTC 229214arm study10111.Pre op RT Sx+/- CT2. Pre op CRTSx +/-CT10.4 Yrs(7.8-13.1)10yrs22.4% vs 11.8% vs 14.5% vs11.7%P –0.001710yr49%vs50.7%vs51.8%vs48.4%P – 0.91No sign. toxicity
Sauer R
et al.
German CAO/ARO/AIO-94
JCO 2012
Bosset
J et.al.
EORTC 22921
Lancet
Oncol
2014Slide11
Long vs Short Course
Chemoradiotherapy
Study
No
of PatientsRandomisationMedian F/U3 yr LRR5 yr OSToxicitylate
Australian
Intergroup trial 2012
326
T3 N0-2 M0
SC – 163
LC
– 163
5.9yrs
7.5%
Vs
4.4%
P – 0.24
74%
Vs
70%
P
– 0.62G 3-45.8 vs 8.2P-0.53Polish rectal cancer group 2006312SC:156LC 15648 mthsHigher pCR in CRT67.2%Vs 66.2%10.1%Vs 7.1%
Tumour
downstaging
/higher
pCR
/
LRR
No conclusive evidence of survival benefit/
sph
sparingSlide12
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 )Slide13
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):45-50.4 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 Slide14
Positioning & immobilisation
Supine/prone
Pelvic thermoplastic mask
CECT simulation
Target volumes:Primary tumour + clinically +ve nodes >1cmEntire mesorectumLymphnodes
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 Slide15
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 Slide16
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. Slide17
O
rgans at risk (OAR) : Dose constraints
Small
bowel
BladderFemoral headNo more than 180 cc above 35 Gy No more than 100 cc above 40 GyNo more than 65 cc above 45 Gy
No more than 40% volume > 40
Gy
No more than 15% volume > 45
Gy
No more than 40% volume > 40
Gy
No more than 25% volume > 45
GySlide18
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
capecitabineSlide19Slide20
Plan evaluation : Dose volume histogramSlide21
M
id rectal cancer: planned for preoperative chemo radiotherapy with intensity modulated radiotherapy
Samuelian
et al IJROBP 2012
Technique CRT vs IMRT GI toxicity(Gr 2) 62% 32%Diarrhoea 48 % 23%Enteritis 30% 10%(p=0.02) No diff in pCR rates Slide22
IMRT Vs CRT
Samuelian
JM et al IJROBP 2012Slide23
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 2007Slide24
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 Slide25
COMPARISON PROTON/3DCRT/IMRT
Colaco
et al J
Gastrointest oncol 2014Slide26
COMPARISION PROTON/3DCRT/IMRT
Colaco
et al J Gastrointest
oncol 2014Slide27
RADIOTHERAPY IN PALLIATIVE SETTING
Symptom based management
Haemostatic Radiotherapy
Local palliative RadiotherapyBone metastasis
Cord compressionBrain metastasis Slide28
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 tumorsNeoadjuvant
CRT : Tumor down staging improved resection/ sph preservation /local control: Current standard of care No evidence of survival benefit . Optimal combination challenge.Slide29
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 Slide30
Thank you