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Opportunity for palliative care Research

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.

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Opportunity for palliative care Research

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

  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

  8. Adverse effects Of Preoperative Radiotherapy

  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 Sauer R et al. German CAO/ARO/AIO-94 JCO 2012 Bosset J et.al. EORTC 22921 Lancet Oncol 2014

  11. Long vs Short Course Chemoradiotherapy 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):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

  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

  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

  19. Plan evaluation : Dose volume histogram

  20. 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

  21. IMRT Vs CRT Samuelian JM et al IJROBP 2012

  22. 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

  23. 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

  24. COMPARISON PROTON/3DCRT/IMRT Colaco et al J Gastrointestoncol 2014

  25. COMPARISION PROTON/3DCRT/IMRT Colaco et al J Gastrointestoncol 2014

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

  27. 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.

  28. 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

  29. Thank you

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