Opportunity for palliative care
Research
Sushmita
Pathy
Role of RadiotherapyDrin
Multidisciplinary
Associate
Professor
Management of Rectal
Cancers
Department of Radiation Oncology
Dr BRA Institute
Dr. Sushmita
Pathy Rotary Cancer Hospital
All India
Institute Of Medical Sciences
Additional
Professor
New Delhi INDIA
Department Of Radiation Oncology
Institute Rotary Cancer Hospital
All India Institute Of Medical Sciences
New Delhi INDIA.
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
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
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 .
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
Preoperative vs Postoperative
approach
o
o
o
o
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
o Post operative RT
o Hypoxic post surgical bed Chemotherapy and RT less
effective
o Higher morbidity : small bowel,large treatment volume
Selectively treat patients with high risk histopath features
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 0.0001
Adverse effects Of Preoperative
Radiotherapy
Study
Swedish rectal cancer trial : Long term
follow –up Birgisson JCO 2005
Swedish rectal cancer trial : Late GI
toxicity Birgisson Br J sug 2008
•Increase in risk for early admissions(6
months) in
irradiated patients RR1.64
•Bowel frequency,
•Incontinence,
•Urgency
Over all quality of life rated good
•Increased RR 2.49of late small bowel
obstruction ,(post op anast leakage)
• Abdominal Pain RR 2.09
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
Preoperative chemoradiotherapy
Trial
No of
Patients
Randomis
ation
Median
F/U
LR
OS
Toxicity
GERMAN
823
Pre op
CRT-405
134
months
(90-184
mo)
10yr
7.1%
Vs
10.1%
P - 0.048
10yr
59.6%
Vs
59.9%
P – 0.85
-
10.4 Yrs
(7.8-13.1)
10yrs
22.4% vs
11.8% vs
14.5% vs
11.7%
P –0.0017
10yr
49%vs
50.7%vs
51.8%vs
48.4%
P – 0.91
No sign.
toxicity
cT3-4
cN+
Post op
CRT-395
EORTC
22921
4arm study
1011
1.Pre op
RT
Sx+/CT
2. Pre op
CRTSx
+/-CT
Sauer R et al. German CAO/ARO/AIO-94 JCO 2012
Bosset J et.al. EORTC 22921 Lancet Oncol 2014
Long vs Short Course Chemoradiotherapy
Study
No of
Patients
Randomisat
ion
Median F/U
3 yr LRR
5 yr OS
Toxicity
late
Australian
Intergroup
trial 2012
326
T3 N0-2
M0
SC – 163
5.9yrs
7.5%
Vs
4.4%
74%
Vs
70%
G 3-4
5.8 vs 8.2
P-0.53
P – 0.24
P – 0.62
Higher
pCR in
CRT
67.2%
Vs 66.2%
Polish rectal
cancer group
2006
312
LC – 163
SC:156
LC 156
48 mths
Tumour downstaging/higher pCR/ LRR
No conclusive evidence of survival benefit/sph sparing
10.1%
Vs 7.1%
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 )
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
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
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
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.
• 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 40% volume > 40
Gy
No more than 25% volume > 45
Gy
•
• 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
Plan evaluation : Dose volume
histogram
Mid rectal cancer: planned for preoperative chemo
radiotherapy with intensity modulated radiotherapy
Technique
CRT vs IMRT
GI toxicity(Gr 2) 62% 32%
Diarrhoea
48 % 23%
Enteritis
30% 10%(p=0.02)
No diff in pCR rates
Samuelian et al IJROBP 2012
IMRT Vs CRT
Samuelian JM et al IJROBP 2012
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
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
COMPARISON PROTON/3DCRT/IMRT
Colaco et al J Gastrointest oncol 2014
COMPARISION PROTON/3DCRT/IMRT
Colaco et al J Gastrointest oncol 2014
RADIOTHERAPY IN PALLIATIVE
SETTING
Symptom based management
• Haemostatic Radiotherapy
• Local palliative Radiotherapy
• Bone metastasis
• Cord compression
• Brain metastasis
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.
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