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![Primary Outcome Measures
• Failure-free survival
• [ Time Frame: 3-year ]
• Is calculated from the date of randomization to the
date of treatment failure or death from any cause,
whichever is first.
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![Secondary Outcome Measures
1. Overall survival [ 3-year ] Overall survival is calculated from
randomization to death from any cause.
2. Loco regional failure-free survival [ 3-year ] The latency (i.e, time
from randomization) to the first loco regional failure
3. Distant failure-free survival [ 3-year ] The latency (i.e, time from
randomization) to the first remote failure
4. The initial response rates after treatments [ Time Frame: A week after
completion of the last cycle of induction chemotherapy and 16 weeks
after completion of radiotherapy ]
5. Toxic effects [ Time Frame: During and after treatment ]
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![Adverse events
Investigation
arm
control arm
Neutropenia 101 [42%] 17 [7%]
Leucopenia 98 [41%] 41 [17%]
Stomatitis 98 [41%] 84 [35%]
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Journal club
- 1. CRITICAL APPRAISAL OF AMEDICAL JOURNAL PRAGATHEESWARI G K
- 2. 8/12/2022 2 G KPRAGATHEESWARI MMC
- 3. 8/12/2022 G KPRAGATHEESWARI MMC 3
- 4. Synopsis ⮚Why this journal ⮚Journalsplit up ⮚Merits ⮚Shortcomings ⮚Final message 8/12/2022 4 G K PRAGATHEESWARI MMC
- 5. 8/12/2022 5 G KPRAGATHEESWARI MMC CFR = 60%
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- 8. Nasopharynx Management MOST COMMONLYPRACTISED and in our institution - CCRT f/b Adj .chemo Some cases- induction chemo f/b CCRT CCRT chemo - CDDP 100mg/m2 every 3weeks - 3cycleS + ADJ chemo - PF / TPF Induction chemo - TPF /PF /Gemcitabine + CDDP 8
- 9. CCRT +/ ICor AC , why not CCRT alone? 1. NPC Chemo responsive than other H&N 2. Other H & N adding chemo - 6.5 % Inc in 5 yr SR MACHNC 3. adding I/C + CCRT - TAX 323 , Improved PFS 4. PARADIGM - 3yr SR 73% vs 78 % , stopped. 5. DECIDE - DFRS- 69 vs 64 % , p value 0.39, NO OS 6. meta analysis by LI et a, chen at al - CCRT >>RT,CCRT provides, DFS,FFS,OS then RT alone. 7. Nasopharynx - RTOG 0099 addition of chemo CCRT + adj chemo , 5yr SR - 67 vs 37%. 8. so- AC + CCRT >> CCRT in NPC , 9. so now what about induction chemotherapy +CCRT?? 9
- 10. • does IC+CCRT will supersede, superior benefits than the commonly practised, AC +CCRT. • so analysing the benefit of IC+CCRT, the LC/DFS/OS is important. 10
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- 13. Journal Split Up •Basic information • Description • Criteria • Analytics • Results • Conclusion 8/12/2022 13 G K PRAGATHEESWARI MMC
- 14. Official Title: Prospective RandomizedTrial Comparing Induction Chemotherapy Plus Concurrent Chemo radiotherapy With Concurrent Chemo radiotherapy in Patients With Loco regionally Advanced Nasopharyngeal Carcinoma Investigators: Study Chair: Jun Ma, M.D. Sun Yat-sen University 8/12/2022 14 G K PRAGATHEESWARI MMC
- 15. • PHASE ;III • TYPE - INTERVENTIONAL CLINICAL TRIAL • DONE - MULTICENTRIC STUDY ,CHINA • ALLOCATION : Randomised • Masking : None ,Open label • Purpose - Treatment • Start date - January 2011 • Completion - April 2016 • Last updated post - February 2014 8/12/2022 15 G K PRAGATHEESWARI MMC
- 16. AIM Induction chemotherapy plus concurrent chemo radiotherapy • concurrentchemo radiotherapy 8/12/2022 16 G K PRAGATHEESWARI MMC
- 17. Investigation arm Induction chemo (TPF) CCRT Control arm - CCRT 8/12/202217 G K PRAGATHEESWARI MMC
- 18. Study Description • Patientspresented with non-keratinizing NPC and stage T3-4N1M0/TxN2-3M0 are randomly assigned to receive • Induction chemotherapy plus concurrent chemo radiotherapy (investigational arm) or • Concurrent chemo radiotherapy (control arm). • Patients are stratified according to the treatment centers and stage. 8/12/2022 18 G K PRAGATHEESWARI MMC
- 19. 8/12/2022 19 G KPRAGATHEESWARI MMC Patients in both arms receive radical radiotherapy, and cisplatin (100mg/m2) every three weeks for three cycles during radiotherapys • RT + INJ.CDDP 100mg/m2 Q3w, 3cycles Patients in the investigational arm receive docetaxel (60mg/m2 on day 1), cisplatin (60mg/m2 on day 1) and fluorouracil (600mg/m2 on Days 1 to 5) every three weeks for three cycles before the chemo radiotherapy. • TPF Regimen Q3w 3cycles, f/b CCRT
- 20. • The primaryend point • Is Failure-Free Survival (FFS). • Secondary end points • Include overall survival (OS), distant failure-free survival (D-FFS), loco regional failure-free survival (LR-FFS), initial response rates after treatments and toxic effects. • All efficacy analyses are conducted in the intention-to-treat population; the safety population include only patients who receive their randomly assigned treatment. 8/12/2022 20 G K PRAGATHEESWARI MMC
- 21. Primary Outcome Measures •Failure-free survival • [ Time Frame: 3-year ] • Is calculated from the date of randomization to the date of treatment failure or death from any cause, whichever is first. 8/12/2022 21 G K PRAGATHEESWARI MMC
- 22. Secondary Outcome Measures 1.Overall survival [ 3-year ] Overall survival is calculated from randomization to death from any cause. 2. Loco regional failure-free survival [ 3-year ] The latency (i.e, time from randomization) to the first loco regional failure 3. Distant failure-free survival [ 3-year ] The latency (i.e, time from randomization) to the first remote failure 4. The initial response rates after treatments [ Time Frame: A week after completion of the last cycle of induction chemotherapy and 16 weeks after completion of radiotherapy ] 5. Toxic effects [ Time Frame: During and after treatment ] 8/12/2022 22 G K PRAGATHEESWARI MMC
- 23. Eligibility Criteria: • AgesEligible for Study: 18 Years to 59 Years (Adult) • Sexes Eligible for Study: All • Accepts Healthy Volunteers: No 8/12/2022 23 G K PRAGATHEESWARI MMC
- 24. Inclusion Criteria: • Newlyhistologically confirmed non-keratinizing WHO histological type. • Tumor staged as T3-4N1/N2-3 (according to the 7th American Joint Commission on Cancer edition). • No evidence of distant metastasis (M0). • Satisfactory performance status: Karnofsky scale (KPS) > 70. • Adequate marrow: • WBC≥4000/μL , Hemoglobin ≥90g/dL and platelet count ≥100000/μL . • Normal liver function test: ALT,AST <1.5×upper limit of normal (ULN) concomitant with ALP ≤2.5×ULN, and bilirubin ≤ULN. • Adequate renal function: creatinine clearance ≥60 ml/min. • Patients must be informed of the investigational nature of this study and give written informed consent. 8/12/2022 24 G K PRAGATHEESWARI MMC
- 25. Exclusion Criteria: • WHOType keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma • Age ≥60 years or <18 years. • Treatment with palliative intent. • Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer. • Pregnancy or lactation. • History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume). • Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes. • Any severe inter current disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance. 8/12/2022 25 G K PRAGATHEESWARI MMC
- 26. Statistics • Between Mar1st, 2011 Aug 22nd, 2013 • median follow-up of 45 months 8/12/2022 26 G K PRAGATHEESWARI MMC
- 27. STATISTICS (hazard ratio 0·68,95% CI 0·48–0·97; p=0·034). 8/12/2022 27 G K PRAGATHEESWARI MMC Investigation arm Control arm 241 patients 239 patients 3-year failure-free survival 80% 72%
- 28. Adverse events Investigation arm control arm Neutropenia101 [42%] 17 [7%] Leucopenia 98 [41%] 41 [17%] Stomatitis 98 [41%] 84 [35%] 8/12/2022 28 G K PRAGATHEESWARI MMC
- 29. Conclusion of thestudy • Addition of TPF induction chemotherapy to concurrent chemo radiotherapy significantly improved failure-free survival in loco regionally advanced nasopharyngeal carcinoma with acceptable toxicity. • Long-term follow-up is required to determine long-term efficacy and toxicities. 8/12/2022 29 G K PRAGATHEESWARI MMC
- 30. Merits of thetrial • Randomized control trial - category 1 evidence in NCCN • The regimen which proven to be more effective is used I.e TPF regimen • Not only the survival rates, but also toxicities compared and analysed • The EBV associated NPC most common cause of NPC worldwide is analysed • Done in CHINA , • Grossly Altered RFT,LFT, Hemogram- were excluded so the survival rate , will not have any variation due to death by other comorbid associated cause. 8/12/2022 30 G K PRAGATHEESWARI MMC
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- 34. 8/12/2022 34 G KPRAGATHEESWARI MMC Global 1,33,354
- 35. Short comings 1. Donein china , the ethnicity varies from other countries 2. Incidence of nasopharyngeal carcinoma and etiology differs from other country residents 3. Studied only EBV associated NPC , -non keratinising type, which is less in India 4. Excluded non EBV associated NPC - keratinising type , which is more common in India 5. Age > 18 years only selected, the significant portion patient could have been missed, as first peak is in age group 15 - 25 years. 8/12/2022 35 G K PRAGATHEESWARI MMC
- 36. • Compared inductionchemo vs CCRT , but not the commonly practiced ccrt f/b adj chemo , hence the much needed results are not met, even in EBV associated NPC • Trial done using 7th edition AJCC staging system. • Induction chemo toxicities - study says it is manageable , and acceptable as it Improves the DFS. but considering the patient load, and available Health care in our country government sector , monitoring and managing haematological toxicities, still remains a major limiting factor for induction or say high dose chemotherapy • Another country/continent , which has high EBV associated NPC - practicing induction chemo with managing these haematological toxicities still remains questionable. 8/12/2022 36 G K PRAGATHEESWARI MMC
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- 40. TO END • Thisstudy provides the back bone evidence for category 1 recommendation of induction chemo plus ccrt in EBV associated NPC • Further analysis and follow-up may provide insight into why the significant decrease in DF did not translate into improved OS.. • For our population, a similar study which compares IC plus CCRT Vs AC plus CCRT , for non EBV associated NPC is needed. 8/12/2022 40 G K PRAGATHEESWARI MMC
- 41. REFERENCE • ClinicalTrials.gov • Pubmed •Globocon 2020 • Frontiers in oncology • Perez & Brady’s Principles and Practice of Radiation Oncology • The AJCC cancer staging manual 7th edition • The AJCC cancer staging manual 8th edition 8/12/2022 G K PRAGATHEESWARI MMC 41
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- 43.