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# Quiz on clinical trials of head &amp; neck day 2

quiz on clinical trials of head and neck cancer

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### Quiz on clinical trials of head &amp; neck day 2

1. 1. Quiz on Clinical Trials of Head & Neck KBC- KAUN BANEGA CHAMPION Day 2 (07-09-2018) By Dr. Ayush Garg
2. 2. TRIALS WHICH ARE COVERED TODAY
3. 3. 1 2 3 4 Question 1 End123456789101112131415161718192021222324252627282930
4. 4. 1 2 3 4 Answer 1
5. 5. Question 2 End123456789101112131415161718192021222324252627282930
6. 6. Answer 2 • The boxes show the effect estimates from the single studies, while the diamond shows the pooled result. • The horizontal lines through the boxes illustrate the length of the confidence interval. The longer the lines, the wider the confidential interval, the less reliable the study results. • The vertical line is the line of no effect (i.e. the position at which there is no clear difference between the intervention group and the control group). • The width of the diamond serves the same purpose. • The last possibility: if the diamond touches the vertical line, the overall (combined) result is not statistically significant. It means that the overall outcome rate in the intervention group is much the same as in the control group. This is the case in the figure above. • If the outcome of interest is adverse (e.g. mortality), the results to the left of the vertical line favour the intervention over the control. That is, if result estimates are located to the left, it means that the outcome of interest (e.g. mortality) occurred less frequently in the intervention group than in the control group (ratio < 1). • If the outcome of interest is desirable (e.g. remission), the results to the right of the vertical line favour the treatment over the control. That is, if result estimates are located to the right, it means that the outcome of interest (e.g. remission) occurred more frequently in the intervention group than in the control group (ratio > 1).
7. 7. Question 3 Match the following? 1. Overall Survival A. The period until metastasis is detected 2. Progression Free Survival B. The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer 3. Distant Metastasis–free Survival C. The time from randomisation until death from any cause 4. Disease Free Survival D. Time from date of randomization to the date of disease recurrence or death from any cause End123456789101112131415161718192021222324252627282930
8. 8. Answer 3 1. Overall Survival C. The time from randomisation until death from any cause 2. Progression Free Survival D. Time from date of randomization to the date of disease recurrence or death from any cause 3. Distant Metastasis–free Survival A. The period until metastasis is detected 4. Disease Free Survival B. The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer
9. 9. Question 4 1. Concomitant Boost 2. Conventional 3. Split Course 4. CHART Type A Type B Type C Type D End123456789101112131415161718192021222324252627282930
10. 10. Answer 4
11. 11. Which is incorrectly matched? TRIAL NAME SITE YEAR UPDATE MARCH META- ANALYSIS HEAD AND NECK 2006 2017 TAX 323 HEAD AND NECK 2007 2011 GORTEC 2000-01 LARYNX 2009 2016 RTOG 91-11 LARYNX 2003 2013 PARSPORT HEAD AND NECK 2011 2016 Question 5 End123456789101112131415161718192021222324252627282930
12. 12. TRIAL NAME SITE YEAR UPDATE MARCH META- ANALYSIS HEAD AND NECK 2006 2017 TAX 323 HEAD AND NECK 2007 2011 GORTEC LARYNX 2009 2016 RTOG 91-11 LARYNX 2003 2013 PARSPORT HEAD AND NECK 2011 2016 Answer 5
13. 13. • Match the following Year & Number of Trials in MACH-NC • A. 2000 1. 87 • B. 2007 2. 87 • C. 2009 3. 93 • D. 2011 4. 63 Question 6 End123456789101112131415161718192021222324252627282930
14. 14. • A. 2000 4. 63 • B. 2007 1. 87 • C. 2009 3. 93 • D. 2011 2. 87 Answer 6
15. 15. • In Update of GORTEC 2000-01 the full form of LDFFS is? TPF PF P value Overall response after NACT 80% 59.2% A 3 years Larynx Preservation Rate 70.3% 57.5% B 5 years Larynx Preservation Rate 74% 58% C 10 years Larynx Preservation Rate 70.3% 46.5% D 5 years LDFFS 67.2% 46.2% E 10 years LDFFS 63.7% 37.2% F Question 7 End123456789101112131415161718192021222324252627282930
16. 16. Answer 7 LDFFS= Larynx DysFunction Free Survival TPF PF P value Overall response after NACT 80% 59.2% 0.002 3 years Larynx Preservation Rate 70.3% 57.5% 0.03 5 years Larynx Preservation Rate 74% 58% 0.68 10 years Larynx Preservation Rate 70.3% 46.5% 0.01 5 years LDFFS 67.2% 46.2% 0.57 10 years LDFFS 63.7% 37.2% 0.001
17. 17. Question 8 *Conventional fractionation or accelerated/hyperfractionated. R A N D O M I Z E Radiation* Follow-up 12 weeks after RT and thereafter TPF Induction (n=177) 4 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 75 mg/m² day 1 fluorouracil 750 mg/m²/day days 1–5 ++ PF Induction 4 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 12 weeks 7 weeks TAX 323: Trial Design Primary endpoint: ???? ???? N=177 N=181 End123456789101112131415161718192021222324252627282930
18. 18. Hint R A N D O M I Z E Radiation* Follow-up 12 weeks after RT and thereafter TPF Induction (n=177) 4 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 75 mg/m² day 1 fluorouracil 750 mg/m²/day days 1–5 ++ PF Induction 4 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 12 weeks 7 weeks TAX 323: Trial Design Primary endpoint: 5 1 2 3 4 N=177 N=181 *Conventional fractionation or accelerated/hyperfractionated.
19. 19. Answer 8 R A N D O M I Z E Radiation* Follow-up 12 weeks after RT and thereafter TPF Induction 4 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 75 mg/m² day 1 fluorouracil 750 mg/m²/day days 1–5 ++ PF Induction 4 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 12 weeks 7 weeks TAX 323: Trial Design Primary endpoint: Progression Free Survival N=177 N=181 *Conventional fractionation or accelerated/hyperfractionated.
20. 20. Question 9 Chemotherapy Meta-Analysis (MACH-NC) Timing No. trials No. pts. HR (95% CI) P-value 5 yr benefit Induction 31 5311 0.96 (0.90 - 1.02) NS 2.4% Adjuvant 12 2567 1.06 (0.95 - 1.18) NS ? Concurrent 50 9615 0.81 (0.78 - 0.86) <0.0001 ? Survival End123456789101112131415161718192021222324252627282930
21. 21. Answer 9 Chemotherapy Meta-Analysis (MACH-NC) Randomized trials 1965-2000 Timing No. trials No. pts. HR (95% CI) P-value 5 yr benefit Induction 31 5311 0.96 (0.90 - 1.02) NS 2.4% Adjuvant 12 2567 1.06 (0.95 - 1.18) NS -1.0% Concurrent 50 9615 0.81 (0.78 - 0.86) <0.0001 6.5% Survival:
22. 22. • Update of March Meta-analysis was published in Lancet 2017 How did they defined altered fractionation? Question 10 End123456789101112131415161718192021222324252627282930
23. 23. • Trials were grouped according to the type of altered fractionation used: • hyperfractionation, which used a higher total dose than the reference group, using twice daily fractions but with the same overall treatment time; • moderate acceleration, in which the total dose was unchanged (―5%) but delivered more quickly (generally about 1 week faster) than in the reference group; • very accelerated radiotherapy with dose reduction, in which radiotherapy duration was shortened by 50% or more and total dose reduced by about 15% (range 11–23) compared with the reference groups Answer 10
24. 24. Question 11 Complete the Conclusion Induction chemotherapy with __________ provides long-term survival benefit compared with ________ in ________________________. Patients who are candidates for induction chemotherapy should be treated with ________________. End123456789101112131415161718192021222324252627282930 Long term results of TAX 324 randomized phase 3 trial published in
25. 25. Answer 11 Complete the Conclusion Induction chemotherapy with TPF provides long-term survival benefit compared with PF in locally advanced head and neck cancer. Patients who are candidates for induction chemotherapy should be treated with TPF.
26. 26. Question 12 End123456789101112131415161718192021222324252627282930 1. What is this curve called? 2. What are the two arms? 3. According to this table tell what is on Y axis? ? PARADIGM TRIAL
27. 27. Answer 12 Kaplan Meier Curve
28. 28. • What was the primary objective of PARSPORT trial? • What was the scale that was used to grade Xerostomia (Name any one)? • What was the scale used to assess Xerostomia? Question 13 End123456789101112131415161718192021222324252627282930
29. 29. • The primary objective was to assess late side-effects. • Patient-reported QoL was collected with questionnaire booklets that contained the EORTC-QLQC30 quality-of-life instrument (which measures generic cancer-related QoL), the associated head and neck specific module HN35, and the modified xerostomia questionnaire. • Patients completed the baseline booklet in the clinic before randomisation. Follow-up booklets were sent directly to the patients’ homes at 2 weeks, 3, 6, 12, 18, and 24 months after radiotherapy. • The primary endpoint, agreed in discussion with the independent trial steering committee, was the proportion of patients with xerostomia of grade 2 or worse by the Late Effects of Normal Tissues Subjective, Objective, Management, and Analytic (LENT SOMA) subjective side-effect scale 1 year after treatment. Answer 13
30. 30. Question 14 End123456789101112131415161718192021222324252627282930
31. 31. Question 14 1. What is this image showing? 2. What are the results of this MA according to OS & age? 3. What is wrong with this image??
32. 32. Answer 14 It’s a Forest Plot
33. 33. • There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3·4% at 5 years (p=0·003). • The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1·7% with total dose reduction at 5 years, p=0·02). • There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6·4% at 5 years; p<0·0001), • The benefit was significantly higher in the youngest patients (hazard ratio 0·78 [0·65–0·94] for under 50 year olds, 0·95 [0·83–1·09] for 51–60 year olds, 0·92 [0·81–1·06] for 61–70 year olds, and 1·08 [0·89–1·30] for over 70 year olds; test for trends p=0·007).
34. 34. Question 15 Tell 5 treatment arms out of 7 used for the study and tell the three arms that were better than others (in terms of OS, PFS, LRcontrol)? End123456789101112131415161718192021222324252627282930
35. 35. Answer 15
36. 36. • The three treatments that had the highest effect on OS were CRT-AC, CRT, and IC-CRT, with respective P-scores (higher score meaning a higher probability of being the best treatment) of 96%, 70%, and 63%, respectively, and corresponding absolute benefit at 5 years of 12%, 8% and 6% compared with radiotherapy alone. • The three best treatments for PFS were CRT-AC being the most effective, with a P-score of 94%, IC-CRT (79%) and CRT (52%) • The three best treatments for locoregional control were ICRT-AC, CRT- AC, and RT-AC, with respective P-scores of 90%, 82%, and 58% Answer 15
37. 37. Question 16 End123456789101112131415161718192021222324252627282930
38. 38. Question 16
39. 39. Answer 16
40. 40. Question 17 1. What is this curve? 2. Identify the two arms? 3. This curve is showing overall survival, what are the results? 4. What is the conclusion of the study? End123456789101112131415161718192021222324252627282930 VA Laryngeal Cancer Study Group (NEJM 1991)
41. 41. 1. Kaplan Meier Curve 2. Induction chemo followed by radiotherapy and surgery followed by radiotherapy 3. Survival rates at 2 years was 68% (p-0.98) 4. For all 166 patients assigned to the chemotherapy group, the estimated rate of Larynx preservation after 2 years was 66%. Hence Larynx preservation better without compromising overall survival. Answer 17
42. 42. Question 18 1. What was the primary result of the study? 2. Primary risk stratification was based on ________________ 3. Secondary risk stratification was based on ________________ 4. Tertiary risk stratification was based on ________________ 5. Quaternary risk stratification was based on ________________ End123456789101112131415161718192021222324252627282930
43. 43. 1. This meta-analysis of eight prospective studies and six retrospective studies including 7 836 patients showed that pre- DNA, mid-DNA, post- DNA and EBV DNA clearance rate were all strongly associated with cancer-specific outcomes (OS, PFS, DMFS and LRFS) in NPC patients. 2. Primary risk stratification was based on pre DNA levels< 4000 copies/mL 3. Secondary risk stratification was based on mid DNA levels 4. Tertiary risk stratification was based on post DNA levels 5. Quaternary risk stratification was based on pre DNA and t1/2 DNA levels < 7 days Answer 18
44. 44. R A N D O M I Z E TPF Induction (n=255) 3 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–4 ++ PF Induction (n=246) 3 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 9 weeks Concurrent CRT carboplatin (AUC 1.5) weekly; 7 doses maximum + Radiation 7 weeks TAX 324: Trial Design Primary endpoint: overall survival Question 19 End123456789101112131415161718192021222324252627282930
45. 45. R A N D O M I Z E TPF Induction (n=255) 3 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–4 ++ PF Induction (n=246) 3 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 9 weeks Concurrent CRT carboplatin (AUC 1.5) weekly; 7 doses maximum + Radiation 7 weeks TAX 324: Trial Design Primary endpoint: overall survival Question 19 1 2 3 4 5
46. 46. R A N D O M I Z E TPF Induction (n=255) 3 cycles, q 3 wk Docetaxel 75 mg/m² day 1 cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–4 ++ PF Induction (n=246) 3 cycles, q 3 wk cisplatin 100 mg/m² day 1 fluorouracil 1000 mg/m²/day days 1–5 + 9 weeks Concurrent CRT carboplatin (AUC 1.5) weekly; 7 doses maximum + Radiation 7 weeks TAX 324: Trial Design Primary endpoint: overall survival Question 19
47. 47. Question 20 Survival curves for overall survival in trials investigating (A) ___________, (B) ________, (C) _________, and (D)_________ End123456789101112131415161718192021222324252627282930
48. 48. Answer 20
49. 49. Answer 20 Survival curves for overall survival in trials investigating (A) induction, (B) adjuvant, (C) concomitant, and (D) concomitant plus adjuvant chemotherapy
50. 50. 2 cycles chemo Response assessment Responders Non Responders Complete this flowchart and tell the chemo regime? Question 21 End123456789101112131415161718192021222324252627282930
51. 51. 2 cycles chemo Response assessment Responders Non Responders 1 more cycle chemo Surgery Radiotherapy Radiotherapy Cisplatin 100mg/m2. 5fu 1000mg/m2 continuous infusion D1 to D5 Answer 21
52. 52. Question 22 End123456789101112131415161718192021222324252627282930
53. 53. Answer 22
54. 54. Question 23 End123456789101112131415161718192021222324252627282930
55. 55. Question 23 • What are the two treatment arms in the Meta-Analysis? • What was defined as Locally advanced Nasopharyngeal Cancers? • What were the three theoretical advantages given about Induction Chemotherapy? ---------------------
56. 56. Answer 23 • Arm 1: Induction Chemo followed by CCRT • Arm 2: CCRT alone • LA-NPX= Stage III to Stage IV, non metastatic • Induction chemotherapy (IC) offers several theoretical advantages: • Firstly, IC is likely to be more tolerable than adjuvant chemotherapy (AC). • Secondly, the use of IC can potentially eradicate early micrometastases. • In addition, IC may debulk the tumour, allowing dose constraints of nearby critical organs at risk to be met, which is advantageous to patients with LA- NPC
57. 57. Answer 23 • Results: There was high quality evidence from the RCTs that IC improved PFS (P = 0.0003) and OS (P = 0.03) significantly and was associated with more frequent AE. • Conclusions: IC delays disease progression and improves survival significantly for LA-NPC treated with CCRT, and was associated with more toxicity. There were no divergent results between RCTs and OBS. IC followed by CCRT can be considered one of the standard treatment options for LA-NPC.
58. 58. • Complete this statement • Grade ___2___ or worse ____2______at ___2____ months was significantly lower in the IMRT group than in the conventional radiotherapy group (p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was _____2____, which was more prevalent in the ____2____ group (p=0.0015) Question 24 End123456789101112131415161718192021222324252627282930
59. 59. Grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (p=0·0015) Answer 24
60. 60. BONUS ROUND BUZZer YOUR SENSES
61. 61. Bonus Question FULL FORM (LENT SOMA) End12345678910
62. 62. Late Effects of Normal Tissues Subjective, Objective, Management, and Analytic (LENT SOMA)
63. 63. FULL FORM (EORTC) 1.EUROPEAN ORGANISATION FOR RADIOTHERAPY OF CANCER 2.EUROPEAN ORGANISATION FOR RADIATION THERAPY AND CHEMOTHERAPY 3.EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER 4.EUROPEAN ONCOLOGY RADIATION THERAPY CENTRE End123456789101112131415
64. 64. FULL FORM (EORTC) 1.EUROPEAN ORGANISATION FOR RADIOTHERAPY OF CANCER 2.EUROPEAN ORGANISATION FOR RADIATION THERAPY AND CHEMOTHERAPY 3.EUROPEAN ORGANISATION FOR RESEARCH AND TREATMENT OF CANCER 4.EUROPEAN ONCOLOGY RADIATION THERAPY CENTRE
65. 65. THANK YOU