Cevical cancer


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  • opsy
  • HR;-hazard ratio / P;- cisplatin / F ;- fluorouracil / HU ;-hydroxyurea
  • Cevical cancer

    1. 1. CERVICAL CANCERDR /Omar Hashim
    2. 2. ANATOMY OF CERVIXThe cervix is the lower 1/3 of the uterus, it is the narrower part of the uterus (neck of uterus) .it is rounded and directed downward and posteriorly .Portio is the portion of the cervix that protrudes into the vagina (about 1cm long and covered by vaginal epithelium .
    3. 3. EPIDEMIOLOGY AND ETIOLOGYCa cervix is the fifth most common cancer in the women worldwide . In USA new case 11,270 and deaths n 4,070 (in2010) .The incidence is ↓ due to screening and human papilloma virus (HPV) vaccines in the past 4th decades .but still in some area in developing countries ca cervix is the most common cancer and leading cause of death .Risk factors ;- early age of sexual intercourse/ high number of lifetime sexual intercourse /exposure to to sexually transmitted diseases (HPV) (AIDS)/smoking / oral contraceptive/DES exposure in utero
    4. 4. PATHOLOGY80% of ca cervix is squamous cell carcinoma (SCC) usually originate at the squamocolumnar junction and progress from mild,moderate,and sever dysplasia to carcinoma insitu, to invasive carcinoma .10%--20% of ca cervix is adenocarcinoma . Usually arise in high endocervical region and originate from endocervical gland .While SCC have ↓ in USA the incidence ofAdenocarcinoma ↑
    5. 5. LYMPH DRAIN & LYMPH SPREAD *Lateral trunk ;-Upper branch → upper internal iliac LNsMiddle branch→obturator LNsLowest branch→gluteal ,common iliac, presacral LNs *posterior trunk ;-Superior rectal LNsSup-aortic LNs (sacralpromontory) *anterior trunk ;-Distal external iliac
    6. 6. INVOLVEMENT OF LNS GROUP( IN%) BYSTAGE Lymph nodes group stage 1 11 111 Pelvic LNs 15% 30% 50% Para-aortic LNs 5% 20% 30%
    7. 7. DIAGNOSISCILNICAL PRESENTATION ;-Abnormal vaginal bleeding > 80% .Vaginal discharge .Late symptoms include symptoms of pelvic organ compression or extension e.g ;-Sciatic pain /lower extremity edemaHydronephrosis /pelvic pain /rectal symptomsUrinary obstruction
    8. 8. INVESTIGATIONinvestigation descriptionTissue diagnosis Pap smear –ve not excluded . biopsy by endocervical curettagelab work CBC to assess HB & CBC and differential Count in anticipation chemotherapy Serum chemistries to assess renal functionImaging studies CXR or chest CT /abdominoplevic CT or MRI which is better in delineation . Or PET which is higher in senitivity in staging LNs or METs
    9. 9. DIAGNOSIS AND PRETHERAPY EVALUATION Ca cervix suspected complete history and physical examinationPhysical exam focus;- Procedure ;- pelvic and Lab ;CBC /blood colposcopy rectovaginal chem/urinalysis Papsmear if no exam/cervical portio Radiology;- bleeding /tumor extension to CXR/Ctor MRI of abd- Biopsy vagina /abd-ex &pelvis OR PET Cold knife conization /supraclavicular LNs
    10. 10. con→ Exam under anesthesia Cystoscopy,proctoscopy Ureteral staging FIGO →radical hysterectomy vs definite radiation chemotherapy
    11. 11. STAGINGGenerally staging depend on history and examination and radiologic and laboratory workup . The most common used staging system is Federation Gynecology and Obstetrics (FIGO) Is based on clinical examation . FIGO permits minimal information from plain radiograph and does not incorporate information on LNs involve-Ment .despite not altering stage categories ,cross sectional imaging (CT/MRI/PET) and invasive surgical staging provide important additional information on the extent of loco regional nodal involvement and distant disease status
    12. 12. FIGO &TNM STAGING OF CA CERVIXFIGO TNM Description - Tx 1ry Tumor not assessed - T0 No evidence of 1ry tumor -a Tis Carcinoma in situ 1 T1 Ca cervix confined to uterus 1A T1a Invasive carcinoma (diag-microscopy) stromal invasion depth 5.0 mm & wide 7.0mm 1B T1b Visible lesion confined to the cervix or mic->7 11 T2 Ca cervix invades out uterus but not pelv-wal 11A T2 a Tumor without parametrial invasion 11B T2b Tumor with parametrial invasion 111 T3 Tumor→plevic wall /lower1/3vagina/affet kid- 111A T3a tumor →Lower 1/3 of vagina/ no plevic wall 111B T3b Tumor→plevic wall or cause hydronephrosis 1v T4 Bladder or rectal invasion 1vA T4a Invade of mucosa of bladder or rectal
    13. 13. CON→ FIGO TNM DESCRIPTION 1VB T4b Mets-peril-/supraclavicular LNs/lunge... 3/4 Nx Reg-LNs not assess 3/4 N0 No regional LNs mets 3/4 N1 Regional LNs mets- 3/4 Mo N o distant mets 3/4 M1 Distant met(peri-/supraclavicularLN or mediastinal LNs
    14. 14. Stage111 enhancement of lift internal iliac lymph nodes
    15. 15. Lymph nodes enhancement in cervical cancer
    16. 16. PROGNOSISCa cervix is curable when diagnosis early ,these lead to improve out come in countries with access heath care and cytological screening .In more advanced disease, tumor recure 1/3 of PTs-. The outcome is improved significantly with theIntroduction of of concurrent chemotherapy in stage 1B2_ 1v A . Neuroendocrine carcinoma of the cervix has ↑mets rate ,poor prognosis and spread in pattern similar to that of small cell cancer .Low HB associated with ↓local control and survival rates specially during RT. Hypoxia also associated with poor out come
    17. 17. stage Local control Disease –free treatment survival1A—1B 93-95% 92% Surgery/Radiatio n 1B All 94% All 81-85% Radiation 4-5cm 90% 4-5cm 86% therapy >5cm 82% >5cm 67% 11A 94– 96% 70– 85% Radiation therapy1B-11 87% 74% Radiation/chemo therapy111—1v 71% 40—50% Radiation /chemotherapy1vB -- 0% Palliative chemotherapy no Radiation
    18. 18. TREATMENT In stage 1A , non bulky 1B ,and early stage 11A , The 1ry treatment is surgery with hysterectomy and 1ry radiation result in similar outcome Stage 1B1 radiation alone a choice or radical hysterectomy . Stage ≥1B2 radiation with concurrent cisplatin based chemotherapy . Treatment modalities ;- surgery ;-Modified radical hysterectomy ;- in which remove done to the uterus ,cardinal ligament , partially the uterosacral ligament ,pelvic LNs .Survival > 95% /preserving ovarian function /avoidance of radiation complication
    19. 19.  Radical hysterectomy ;- For stage 1A2 with LVS1 IB1 , non bulky 1B2 – 11A. In which remove done to the uterus .cardinal ligament & upper 1/3 of the vagina /pelvic LNs . Survival 80—90% . Radiation ;- used to as definitive treatment for stage 1—11A inside of surgery . Definitive treatment for stage 11B– 1VA with concurrent chemotherapy . For bulky disease >5—6cm should complete in 7weeks .stage 1B-11A . Postoperative pelvic radiation for involved LNs +ve SM (EBRT integrated with brachytherapy ) .RT
    20. 20. Diagnosis of ca cervix Clinical and radiological staging Stage 1A– B1 Stage 1B– 11A Stage 11B– 1vA RH/pelvicL Ndissect- RH pelv ERBT+BT/ ±PALN LN disse- CH sam- PA samp OR or ↑ ↑ ERBT +BTERBT+BT risk/LV/de risk/SM/LN /CH pth inve- /param- Post op- RA- Post op radia- Concu-chem- Follow up
    21. 21. CHEMOTHERAPYAS part of definitive treatment with concurrent with RT for locally advanced cervical cancer.Stage 1B1 concurrent CH not validated. AdjuvantCH following concurrent RT/CH may↓ overall recurrence rate used for palliation for local, regional or systemic disease.We use weekly cisplatin during 5weeks with pelvicEBRT with or without CH during BT.3-weekly cisplatin/5-FU is also validated levelEvidence. No benefit to cisplatin to other CH.5-FU alone is not recommended .
    22. 22. Tow randomized trial defined the 1)utilizing of the adjuvant radiation ,and 2)adjuvant radiation with concurrentchemotherapy after hysterectomy Eligibility criteria arm 1 arm2 LVS1 stromal tumor Pelvic RT 46GY in 23 Observation +ve deep1/3 any size fr . 50.4 GY in 28 fr . +ve middle1/3 ≥2cm N=140 n= 137 + ve superficial1/3 ≥5cm -ve deepormidlle ≥ 4cm
    23. 23. In the first trial show 46% reducation in risk of recurrence favoring RT arm (p=0.0007) . Deferent in overall survival
    24. 24. The 2nd trial 109 evaluated addition of concurrentCH. Taking stage 1A,1B, or 11A (LN +ve /paramet-+ve /SM +ve). Pts treated with RH then randomizedTo RT alone versus RT with 4 cycles of cisplatin/5FU. Overall survival was significantly improve.Analysis show particular benefit for large tumor,Multiple LNs.HR for overall survival was 1.96 (p=0.007) favoringRT/concurrent CH. OS for 4 yrs 71% with R and81% for with RT/CH.
    25. 25. Clinical stage 1A,1B ,11A + any of ;- 1- +ve LN S 2- +ve parametria 3- +ve SM randomization ARM1 ARM2Plevic RT 49.3GY IN 29 fr Same RT + Cisplatin /5fu96 hours infusion n=116 Every 3weeks x4 cycles n=127 GOG protocol 109 evaluated the addition of concurrent chemotherapy Is of benefit .*HR overall survival was 1.96 (p=0.007) favoring concurrent Chemo-overall survival was 4 yrs 71% with RT .and 81% with RT+CHEMO-
    26. 26. Trial FIGO Number Compari- Follow up HR ↑ in stage Of pts son survival GOG85 11B-1VA 368 PF veru- 8.7 yrs 0.7 10% HU RTOG 1B(>5cm) 388 PF veru- 43 0.59 15%9001 -1vA none months GOG 11B-1VA 526 P /HU 35 0.61 18% 120 11B-1VA 526 PFHU/H months 0.58 18% U 35 monthGOG 1B(>5cm 369 P versus 36 0.54 9%123 -1vA none monthsNCI/cana 1B(>5cm 253 P versus 64 0.91 3%da -1vA none monthsmeta 1B-1VA 3,452 cth/none 62 0.78 ¾%analysis months Level evidence for the benefit from 5 randomized trial evaluating radiation With concurrent cisplatin base cth-
    27. 27. RT TECHNIQUESDefinitive RT ;-The definitive RT for ca cervix require EBRT (withPelvic and parametrical and nodal boosts if approp-Riate) and BT . Treatment must be individualized based on the patient‘s tumor extend ,normal tissue anatomy ,tumor response characteristics duringThe therapyEBRT ;- the field include 1ry tumor /local extension(parametria / uterosacral ligament, vagina) drainingRegional LNs,
    28. 28. Simulation, target volume delineation & field arrangement ;-3-dimensional image- guide is high recommended toImprove the delineation of target structures andExclusion of normal tissues include bowel ,bladderAnd bone marrow . By use of intravenous contrastFor CT can differentiate regional LNs from vesselsCT can not differentiate tumor from normal tissuesIn side the uterus ,so we use the MRI which showUs the tumor extend in the uterus,parametria,
    29. 29. 1ry tumor GTV ;-entire uterus and tumor extension to para- Metria based on imagi & implanted markers CTV ;-additional 0.7 to 1cm margin,3-cm margin to lower extension PTV 0.5 -1cm margin LNs Gross involved lymph nodes CTV;- gross involved LNs+ 1cm margin in obturator,external and common iliac LNs in 111A In distal half vagina inginal LNs. Post surgical clips &post operative seroma add0.7-cm/1-2 cm anterior to theS1-S3 PTV ;-0.5 –cm marginTarget volume for definitive radiation therapy using Ctbased planing
    30. 30. The final PTV = 1ry tumor PTV +nodal PTV and because ofThe viabilities in the aortic bifurcation 40% of common iliac LNs are be higher to the L4-L5 interspace ,so in these caseThe upper border can shifted up word by 1-3 vertebrae .Contouring of normal structure include the rectum (up to the recto sigmoid junction), bowel (large bowel &mesentery)With in 5cm upper border of target, the bladder and femoralHead .if 3D NOT available the field design should be guidedBy bony landmark
    31. 31. field bordersAP/PA Superior; L4-L5 interspaced Inferior ;- 3cm bellow the lowest tumor extend (determined by Gold seed or bottom of obturator formen . Lateral ;- 2cm lateral to the pelvic brim and include any surgical clips with 1-1.5 cm marginlateral superior;- same as AP/PA inferior ;- same as AP/PPA . Anterior ;- 1cm anterior to pubic pubic symphsis . Posterior ;- at least anterior half of the sacrum
    32. 32. Dose and treatment delivery ;-The EBRT prescribed dose to the range 45– 50.4 GY IN 1,8GY.the BT boost 5.4—14.4 .The total dose will be 50 in small stage 1B.and 55 GY in moderately involved parametrial involved. And 60 GY forBulky parametrial .IMRT ;- is used in the treatment of the ca cervix and show to decrease the dose to the organ at risk (bowel,bladderAcute gasterointestinsl toxicity and bone marrow dose
    33. 33. Regreesion of cervical cancer after 30 GY RT Compare lift and right