Presentation on theme: "Opportunity for palliative care Research"— Presentation transcript:
1 Opportunity for palliative care Research Role of Radiotherapy in Multidisciplinary Management of Rectal CancersDr Sushmita PathyAssociate ProfessorDepartment of Radiation OncologyDr BRA Institute Rotary Cancer HospitalAll India Institute Of Medical SciencesNew Delhi INDIADr. Sushmita PathyAdditional ProfessorDepartment Of Radiation OncologyInstitute Rotary Cancer HospitalAll India Institute Of Medical SciencesNew 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 regionsIndia 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 standardProven benefits of total mesorectal excisionParallel to improvement in surgical technique adjuvant therapy reduce local recurrence rateDramatic 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 limitationAdjuvant radiotherapy preop/post op significant increase in loco-regional controlSphincter sparing procedure . Organ preservationNo improvement with DFS,OS and distant metastasisRole 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+CRT227 patients B2 ,C(R0 resection)10 yr OS 45 % vs 27%,LRR 10% vs 25%Significant benefit with CRTNSABP R-01(1988)3 arm RCT500 patientsPT3/T4N+S/S+CT/S+RTS+CT: Improved DFS& OSS+RT: Reduction in LRR 16% vs 25 % favouring RT No survival benefit
6 Preoperative vs Postoperative approach Pre-operative RTTumour downstaging and improve resection,Better toleranceHigher 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 volumeSelectively treat patients with high risk histopath features
7 Short Course Preoperative Radiotherapy StudySwedish Rectal cancer TrialFolkesson J et al JCO 2005PreopRT vs sug alone116825Gy/5Fr/5days→SugMed FU 13 yearsOS 38% vs30%, p 0.008LRR 9%vs 26% p 0.008Dutch study CKVO 95-04Willem VG et al Lancet oncol 2011PreopRTvs TME alone1861 patients25Gy/5Fr/5days→TMEMed FU 10 yearsOS 48%vs 49% p 0.86LR 5% vs 11% p
8 Adverse effects Of Preoperative Radiotherapy StudySwedish 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 goodSwedish rectal cancer trial : Late GI toxicity Birgisson Br J sug 2008Increased 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 careTumour downstagingImproved resection.Increased sphincter preservationHigher pCR/local controlGerman rectal cancer Trial :Preop CRT vs Post op CRTT3/4,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 TrialNo of PatientsRandomisationMedian F/ULROSToxicityGERMANcT3-4cN+823Pre op CRT-405Post op CRT-395134 months( mo)10yr7.1%Vs10.1%P59.6%59.9%P – 0.85-EORTC 229214arm study10111.Pre op RT Sx+/- CT2. Pre op CRTSx +/-CT10.4 Yrs( )10yrs22.4% vs 11.8% vs 14.5% vs11.7%P –0.001749%vs50.7%vs51.8%vs48.4%P – 0.91No sign. toxicitySauer R et al. German CAO/ARO/AIO-94 JCO 2012Bosset J et.al. EORTC Lancet Oncol
11 Long vs Short Course Chemoradiotherapy StudyNo of PatientsRandomisationMedian F/U3 yr LRR5 yr OSToxicitylateAustralian Intergroup trial 2012326T3 N0-2 M0SC – 163LC – 1635.9yrs7.5%Vs4.4%P – 0.2474%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/ LRRNo conclusive evidence of survival benefit/sph sparing
12 MULTIDISCIPLINARY MANAGEMENT : WHERE ARE WE GOING? Benefits of RT/CRT Vs BurdenIdentify the patients at low risk of local recurrence, and ideally may not benefit from neo-adjuvant therapyPrognostic 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 days11days/3-4 weeks Improved pCR Oncological outcome ?Acute radiation reaction subside after RTLong Course(CRT): Gy/25 fractions/5 weeksMore pronounced tumor regression pCR with prolonged intervalOncological outcome ? Data lackingNo reason to delay beyond 6-8 weeksGlimelius Front oncol 2014
15 INNOVATIONS IN RADIATION THERAPY Three dimensional RT standard of careNew 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 bowelProton 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 designingDose calculation.Plan optimization and evaluation.Treatment documentation and set up verification.
17 Organs at risk (OAR) : Dose constraints Small bowelBladderFemoral headNo more than 180 cc above 35 GyNo more than 100 cc above 40 GyNo more than 65 cc above 45 GyNo more than 40% volume > 40 GyNo more than 15% volume > 45 GyNo 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
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 toxicitySermeus et al World J Gastro 2014De Ridder et al IJROBP 2007
24 PROTON THERAPY Bragg peak is the characteristic of proton beam Spread out Bragg peak (SOBP) summation of multiple beamSharp dose fall off spares tissue surrounding targetNo 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 managementHaemostatic RadiotherapyLocal palliative RadiotherapyBone metastasisCord compressionBrain metastasis
28 ConclusionMultimodal 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.
29 ConclusionLong 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