Cancer Cervix- NACT vs RT+CCT

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Cancer Cervix- NACT vs RT+CCT

  1. 1. Three things we can all agree on:
  2. 2. Three things we can all agree on: <ul><li>1. We “wish nothing but the most effective method of treatment for our patients” </li></ul>
  3. 3. Three things we can all agree on: <ul><li>1. We “wish nothing but the most effective method of treatment for our patients” </li></ul><ul><li>2. The treatment should not be more dangerous than the disease itself. </li></ul>
  4. 4. Three things we can all agree on: <ul><li>1. We “wish nothing but the most effective method of treatment for our patients” </li></ul><ul><li>2. The treatment should not be more dangerous than the disease </li></ul><ul><li>3. We need to avoid what is unnecessary, harmful and excessively expensive. </li></ul>
  5. 5. NACT+ Surgery vs CCT-RT in locally advanced Ca Cervix <ul><li>NACT has no place in current std of care . </li></ul>
  6. 6. NACT+ Surgery vs CCT-RT in locally advanced Ca Cervix <ul><li>NACT has no place in current std of care . </li></ul><ul><li>CCT-RT is the Standard of Care </li></ul>
  7. 7. NACT+ Surgery vs CCT-RT in locally advanced Ca Cervix <ul><li>NACT has no place in current std of care . </li></ul><ul><li>CCT-RT is the Standard of Care </li></ul><ul><li>Surgery is no better than CCT-RT </li></ul>
  8. 8. NACT+ Surgery vs CCT-RT in locally advanced Ca Cervix <ul><li>NACT has no place in current std of care . </li></ul><ul><li>CCT-RT is the Standard of Care </li></ul><ul><li>Surgery is no better than CCT-RT </li></ul><ul><li>In fact it adds to morbidity,length,expense. </li></ul><ul><li>Then why operate and subject the patient to TRIPLE THERAPY </li></ul>
  9. 9. Clinical trials Randomised trials Meta-analysis NCCN practice guidelines NCI practice guidelines MDACC/MSKCC
  10. 10. <ul><li>Toxic effects of para-aortic radiation is greater than pelvic radiation alone, but was mostly confined to patients with prior abdominopelvic surgery. </li></ul>
  11. 16. Metanalysis <ul><li>1: Cochrane Database Syst Rev. 2004;(2):CD001774. Neoadjuvant chemotherapy for locally advanced cervix cancer.Neoadjuvant Chemotherapy for Cervical Cancer Meta-Analysis Collaboration (NACCCMA ) </li></ul><ul><li>OBJECTIVES : This systematic review and individual patient data (IPD) meta-analysis aimed to assess the effect of neoadjuvant chemotherapy in two comparisons: (1) neoadjuvant chemotherapy followed by radical radiotherapy compared to the same radiotherapy alone ; and </li></ul><ul><li>(2) neoadjuvant chemotherapy followed by surgery compared to radical radiotherapy alone . </li></ul>Eur J Cancer. 2003 Nov;39(17):2470-86. NACT-SX RT Alone NACT-RT RT Alone
  12. 17. Metanalysis (NACCCMA) <ul><li>MAIN RESULTS: In the first comparison, we obtained data from 18 trials and 2074 patients. When all trials were considered together, a high level of statistical heterogeneity suggested that the results could not be combined indiscriminately. A substantial amount of heterogeneity was explained by separate analyses of groups of trials. </li></ul><ul><li>Trials using chemotherapy cycle lengths shorter than 14 days (HR = 0.83, 95% CI = 0.69 to 1.00, p = 0.046) or cisplatin dose intensities greater than 25 mg/m2 per week (HR = 0.91, 95% CI =0.78 to 1.05, p = 0.20) tended to show an advantage for neo adjuvant chemotherapy on survival. </li></ul><ul><li>In contrast, trials using cycle lengths longer than 14 days (HR =1.25, 95% CI = 1.07 to 1.46, p = 0.005) or cisplatin dose intensities lower than25 mg/m2 per week (HR = 1.35, 95% CI = 1.11 to 1.14, p = 0.002) tended to show a detrimental effect of neo adjuvant chemotherapy on survival. </li></ul><ul><li>In the second comparison, data from 5 trials and 872 patients were obtained. The combined results from all trials (HR = 0.65, 95% CI = 0.53 to 0.80, p = 0.0004) indicate da highly significant reduction in the risk of death with neo adjuvant chemotherapy, but there were some differences between trials in their design and results. </li></ul>NACT-RT Vs RT Alone NACT-Surgery Vs RT Alone
  13. 18. Metanalysis (NACCCMA) : REVIEWERS' CONCLUSIONS: <ul><li>Despite some unexplained heterogeneity, the timing and dose intensity of cisplatin-based neoadjuvant chemotherapy appears to have an important impact on whether or not it benefits women with locally advanced cervical cancer and warrants further exploration. </li></ul>
  14. 19. Metanalysis (NACCCMA)
  15. 20. 3 rd Metanalysis -Cancer Treat Rev. 2003 Oct;29(5):389-99. Modern management of locally advanced cervical carcinoma. Duenas-Gonzalez A, Cetina L, Mariscal I, de la Garza J.Unidad de Investigacion Biomedica en Cancer, Instituto Nacional de Cancerologia,Instituto de Investigaciones Biomedicas, UNAM, 14080 Tlalpan, Mexico. <ul><li>Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over </li></ul><ul><li>radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. </li></ul>
  16. 21. Meta analysis 4: Eur J Cancer . 1999 Mar;35(3):406-9. Can the published data tell us about the effectiveness of neoadjuvantchemotherapy for locally advanced cancer of the uterine cervix?Tierney JF, Stewart LA, Parmar MK.MRC Clinical Trials Unit, Cambridge, U.K. <ul><li>Meta-analyses of the published data at 2 and 3 years are neither clearly in favour of neoadjuvant chemotherapy nor control (2 years: odds ratio(OR) = 1.09, 95% confidence interval (CI) = 0.83-1.45, P = 0.37; 3 years: OR = 0.96, 95% confidence interval (CI) = 0.73-1.25, P = 0.45). Being restricted to only some of the data from a relatively small fraction of the randomised trials, these analyses potentially suffer from a number of biases and are therefore inconclusive. </li></ul>
  17. 22. Meta-analysis 5 :Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):889-96. Neoadjuvant chemotherapy followed by radiotherapy should not be a standardapproach for locally advanced cervical cancer.Shueng PW, Hsu WL, Jen YM, Wu CJ, Liu HS.Department of Radiation Oncology, Far Eastern Memorial Hospital, Taipei, Taiwan, <ul><li>RESULTS : Several investigators did obtain promising results from Phase II trials of neo adjuvant chemotherapy, mostly cisplatin -based combinations, followed by radiotherapy. However, most Phase III trials failed to demonstrate any benefit in terms of loco-regional relapse and/or survival by up-front chemotherapy . CONCLUSION: The role of neo adjuvant chemotherapy remains to be defined, and the search for more active new agents must be continued. The neo adjuvant setting is still experimental and could not be recommended as a standard treatment at the present . </li></ul>
  18. 23. 12% benefit in overall survival:
  19. 26. NACT+ Surgery vs CCT-RT in locally advanced Ca Cervix <ul><li>NACT has no place . </li></ul><ul><li>CCT-RT is the Standard of Care </li></ul><ul><li>Surgery is no better than CCT-RT </li></ul><ul><li>In fact it adds to morbidity,length,expense. </li></ul><ul><li>Then why operate and subject the patient to TRIPLE THERAPY </li></ul>
  20. 27. Trials favouring NACT-surgery <ul><li>1. Sardi et al (Rand trial): </li></ul><ul><li>RH-RT vs NACT-RH-RT </li></ul><ul><li>Similar outcome at 4 yr for tumor <4cm </li></ul><ul><li>Better 4 yr survival for tumor > 4cm </li></ul><ul><li>2. Benedetti-Panici et al: </li></ul><ul><li>NACT-surgery vs Rt alone </li></ul><ul><li>(Ib-IIa,RT alone,Low dose, freq protracted) </li></ul>
  21. 28. NACT-Surgery trials <ul><li>Chang et al (Rand trial):124 patients </li></ul><ul><li>NACT-Sx vs RT alone: No benefit </li></ul><ul><li>Mendelhall 1991(Bulky >6cm):RT-Sx vs RT </li></ul><ul><li>Eifel 1526 pts Ib 7-7.9cm central rec rate <10% small margin of improvement </li></ul><ul><li>Keys GOG >4cm RT-Extraf Hyst No Benefit </li></ul><ul><li>No Role Except in select gp- With Fibroids/fundus involvement </li></ul>
  22. 29. Clinical trials Randomised trials Meta-analysis NCCN practice guidelines NCI practice guidelines MDACC/MSKCC
  23. 30. MDACC <ul><li>What do they practice at M.D. Anderson Cancer Centre? </li></ul>
  24. 36. Clinical trials Randomised trials Meta-analysis NCCN practice guidelines NCI practice guidelines MDACC/MSKCC
  25. 37. NCCN <ul><li>What is their recommendation? </li></ul>
  26. 47. Clinical trials Randomised trials Meta-analysis NCCN practice guidelines NCI practice guidelines MDACC/MSKCC
  27. 48. NCI GUIDELINES
  28. 49. Do not close the door to future investigations
  29. 51. <ul><li>EGF, VEGF modulators, </li></ul><ul><li>Tomotherapy (Tomorrow) </li></ul><ul><li>Improving further upon present day therapies (better chemotherapeutic drugs, better Rt techniques, radio and cytoprotection) </li></ul><ul><li>Better understanding of antiviral vaccines </li></ul>
  30. 56. CCT-RT NACT surgery
  31. 57. Take home message….
  32. 58. Take home message…. <ul><li>In our routine clinical practice, we should limit ourselves to standard treatment guidelines that are universally accepted. </li></ul>
  33. 59. Take home message…. <ul><li>In our routine clinical practice, we should limit ourselves to standard treatment guidelines that are universally accepted. </li></ul><ul><li>Experiments should only be done in the setting of a CLINICAL TRIAL. </li></ul>
  34. 60. Take home message…. <ul><li>In our routine clinical practice, we should limit ourselves to standard treatment guidelines that are universally accepted. </li></ul><ul><li>Experiments should only be done in the setting of a CLINICAL TRIAL. </li></ul><ul><li>For locally advanced cancer cervix, Concurrent chemoradiation is the current standard of care and </li></ul><ul><li>NOT NACT Surgery </li></ul>
  35. 61. What else can I say? Ab to maan jayo.. Meta-analysis Randomized trials Clinical trials NCI practice guidelines NCCN MDACC DeVita

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