Opportunity for palliative care Research

Transcription

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 o Pre-operative RT o Tumour downstaging and improve resection, o Better tolerance o 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

7 Short Course Preoperative Radiotherapy Study Swedish Rectal cancer Trial Folkesson J et al JCO 2005 Dutch study CKVO Willem VG et al Lancet oncol 2011 PreopRT vs sug alone Gy/5Fr/5days Sug Med FU 13 years OS 38% vs30%, p LRR 9%vs 26% p 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 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

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 Trial GERMAN ct3-4 cn+ EORTC arm study chemoradiotherapy No of Patients Randomis ation 823 Pre op CRT-405 Post op CRT Pre op RT Sx +/- CT 2. Pre op CRT Sx +/-CT Median F/U 134 months ( mo) 10.4 Yrs ( ) LR OS Toxicity 10yr 7.1% Vs 10.1% P yrs 22.4% vs 11.8% vs 14.5% vs 11.7% P yr 59.6% Vs 59.9% P yr 49%vs 50.7%vs 51.8%vs 48.4% P No sign. toxicity Sauer R et al. German CAO/ARO/AIO-94 JCO 2012 Bosset J et.al. EORTC Lancet Oncol 2014

11 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 T3 N0-2 M0 SC 163 LC yrs 7.5% Vs 4.4% 74% Vs 70% G vs 8.2 P-0.53 P 0.24 P 0.62 Polish rectal cancer group SC:156 LC 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 neoadjuvant 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

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 40% volume > 40 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

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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% 32% Diarrhoea 48 % 23% Enteritis 30% 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

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

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