COMPLEMENTARY PROCEDURES USG CT/MRI PET SURGICAL STAGING (Aid in Tx Planning but can’t be used to determine or change FIGO stage)
FIGO STAGING Stage 0 Preinvasive carcinoma / carcinoma in situ Stage I Tumour confined to cervix. IA Preclinical invasive ca, diagnosed by microscopy only. IA1 Measured Stromal Invasion 3mm or less in depth and 7 mm or less in horizontal spread. IA2 Measured stromal invasion 3 to 5mm and 7 mm or less in horizontal spread. IB Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2. IB1 4 cm or less in size. IB2 >4 cm in size. contd.
Stage II Tumour beyond uterus but not the lower 1/3 of vagina or up to the pelvic side walls. IIA without Parametrial invasion.(IIA1:<4 cm; IIA2:>4 cm) IIB with Parametrial invasion. Stage III Tumour extending up to pelvic wall, lower 1/3 vagina, hydronephrosis or non-functioning kidney. IIIA No extension to pelvic wall but involved lower 3rd vagina. IIIB Extension to pelvic side wall, hydronephrosis or non- functioning kidney. Stage IV IVA Invasion of mucosa of bladder/rectum, and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4). IVB Distant Metastasis.
PATHOLOGIC CLASSIFICATION SQUAMOUS CELL CARCINOMA - OVER 90% ADENOCARCINOMA - 7 to 10% OTHERS -1 to 2%
STAGE WISE MANAGEMENT STAGE 0 (Carcinoma In Situ) If FERTILITY PRESERVATION DESIRED For Ectocervical Lesions: Loop electrosurgical excision procedure (LEEP). Laser therapy Cryotherapy Conization If Endocervical Canal Involved: Conization
Treatment of stage 0 contd. POST MENOPAUSAL PATIENTS Total abdominal or vaginal hysterectomy MEDICALLY INOPERABLE Intracavitary Irradiation Alone - 45 to 50 Gy to Point A
STAGE I A I A1 ( No LV Invasion) CONIZATION: Adequate in those who desire fertility. TOTAL HYSTERECTOMY( Abdominal or Vaginal) (also in cone margin positive patients)
Treatment of Stage IA1 contd. INTRACAVITARY BRACHYTHERAPY ALONE Patients unfit for surgery. Dose: 60 to 70 Gy to Point A LV Invasion- Treated Similar to IA2/IB1
STAGE IA2 Radical Hysterectomy with Pelvic Node Dissection Women not fit for surgery: Brachytherapy plus External Pelvic Irradiation( Point A dose: 75 to 80 Gy).
STAGE IB1 and IIA (<4 cm) Radical Hysterectomy plus Pelvic Node Dissection OR Pelvic RT plus Brachytherapy (Point A Dose: up to 80 Gy)
The ABS recommendation: DEFINITIVE RT/RADICAL SURGERY Results Equivalent. The ABS recommends that primary therapy should avoid routine use of both Radical Surgery and RT to minimize morbidity related to multimodality therapy.
STAGE IB2 and Bulky IIA(>4cm) Pelvic RT + Concurrent Cisplatin containing Chemotherapy+ Brachytherapy ( Point A Dose: 85 Gy or more) Radical Hysterectomy + Pelvic Node dissection (lower evidence)
INDICATIONS OF ADJUVANT TREATMENT (Post Operative) NODE NEGATIVE PATIENTS PELVIC IRRADIATION in pts. with any 2 of the following: > 1/3rd Stromal Invasion LV space Invasion Large (>4 cm) tumor
Adjuvant Treatment Contd. Positive Pelvic Nodes/Positive Surgical margin/Positive Parametrium Pelvic RT+ Concurrent Cisplatin based chemotherapy and vaginal brachytherapy if positive vaginal margin.
STAGES IIB/IIIA/IIIB Pelvic RT + concurrent Cisplatin based chemotherapy + Brachytherapy ( Total Point A Dose 85 Gy or more) STAGE IVA Individualized Tx based on Extent of Bladder/Rectal involvement/Renal function/Parametrial involvement/performance status.
Stage IVA Treatment Contd. Surgical Exenteration: Pts with no/minimal parametrial invasion and good performance status( anterior/posterior or total). Concurrent RT/CT: Selected pts with good general and renal status and not suitable for surgical exenteration. Palliative RT: Majority have poor GC and extensive local disease – best treated with Palliative RT alone. A short regime of 30 Gy/10#/2 wks- few pts who respond well-followed by intracavitary appl.
Stage IVB Palliative RT: Palliation of distant metastases in Brain/Bone etc. Palliation of symptoms like pain/bleeding/tenesmus etc. Palliative CT: No standard CT regimen available. Combinations like Cisplatin/Paclitaxel, Cisplatin/Topotecan, Cisplatin/Ifosfamide have been used with varying response rates.
CONCURRENT CHEMORADIATION ABS/NCI Recommend the addition of Cisplatin based CT during the course of definitive RT for stage IB2 onwards. 5 Randomized Trials- significant improvement in local control+ survival (In women from affluent countries with better performance/nutritional status and renal parameters).
CCRT IN INDIAN CONTEXT: Our Patients- lower socioeconomic status/ more advanced disease/poor renal parameters/doubtful compliance/doubtful tolerance to CCRT RADICAL RT ALONE CAN STILL BE CONSIDERED AS AN ACCEPTABLE TREATMENT APPROACH
POST TREATMENT RESULTS ( 5 year DFS ) IA: >95%(With LV Invasion) up to 90%IB 1 : 86-90%IIA( Non bulky) : 75%IB 2/IIA Bulky: 60-65%
Post treatment results contd.( 5 yr survival)STAGE IIB: 60-65% with RT aloneSTAGE III: 30-55% with RT aloneSTAGE IVA:18-30% with Exenteration/RT
INVASIVE CANCER FOUND AFTER SIMPLE HYSTERECTOMY TWO TREATMENT OPTIONS:1. Immediate Resurgery- Radical Parametrectomy and Pelvic LND.2. Post op RT: a) No disease/microscopic only at margins: Whole Pelvis RT 45-50 Gy with Concurrent Cisplatin based Chemotherapy for Microscopic disease at margins, followed by ICRT to boost the dose at vaginal apex to 60-65 Gy (Total dose). b) Gross Residual in vault: Whole Pelvis 40 Gy + parametrium additional 20 Gy, with Concurrent Cisplatin based Chemotherapy followed by ICRT up to 65 Gy mucosal dose.
RECURRENT DISEASEPost RT: 1. Central Disease Small lesions Radical Hysterectomy or Brachytherapy Larger lesions, good PS Pelvic Exenteration 2. Pelvic Side Wall Recurrence Palliative CT/Symptomatic& supportive care.Post Surgery: Definitive Pelvic RT+ Cisplatin based chemotherapyExtrapelvic/Distant Mets: Palliative Intent
RADIOTHERAPY EXTERNAL IRRADIATION- Treats Whole Pelvis+ Parametria ICRT- primarily irradiates central disease( cervix, vagina and medial parametria)EBRT delivered before ICRT If :1) Bulky cervical lesions to improve the geometry2)Exophytic, easily bleeding tumors3)Tumors with necrosis or infection4) Parametrial involvement
EBRT PORTAL: PELVIC AP/PA Borders:Superior Border: L4-L5 Interspace (up to common iliac nodes)Inferior Border: Lower border of the Obturator Foramen.Entire length down to introitus, if vaginal involvement.Lateral Border: 2 cm lateral to bony pelvis on either side.
LATERAL PORTALAnterior Margin: Cortex of symphysis pubis ( cover ext. iliac nodes)Posterior Margin: Covers atleast 50% of rectum in stage IB and extends to Sacral hollow in more advanced tumors.LATERAL FIELDS ALLOW A DECREASE IN DOSE TO THE SMALL BOWEL AND A PORTION OF THE LOW RECTUM BUT CARE MUST BE TAKEN TO INCLUDE ALL STRUCTURES OF INTEREST.
MIDLINE SHIELDING May be used for Part of Pelvic RT to Shield Bladder and Rectum to allow a higher dose to be given by brachytherapy Simple Rectangular Block: 4 cm wide at midplane. Customized midline blocks based on radiographs. When inserted before 40 Gy, should not extend to top of the pelvic field ( C. iliac& presacral nodes shielded).
BRACHYTHERAPY ABS strongly recommends that:1) Definitive Irradiation for cervical carcinoma must include brachytherapy as a component.2)Precise applicator placement is essential for improved local control and reduced morbidity.3)Interstitial brachytherapy should be considered for patients with disease that can’t be optimally encompassed by intracavitary brachytherapy.4)Total treatment duration be less than 8 weeks when possible( exceeding beyond 8 wks can reduce local control and survival by about 1% per day of prolongation.
Treatments Classified with respect to Source loading: 1) Preloading: The applicator is preloaded and contains radioactive sources at the time of placement into the patient.2) Afterloading: The applicator is placed first into the target position and the radioactive sources are loaded later, either by hand (MANUAL) or by a machine( REMOTE AFTERLOADING).
Treatments Classified with respect to DoseRate:LDR: 0.4 – 2 Gy/hrMDR: 2- 12 Gy/hrHDR: > 12 Gy/hr ( practically much higher dose rate used)
EVOLUTION OF BRACHYTHERAPY IN CARCINOMA CERVIXFirst application of Radium in treatment ofuterine cancer- 1908Three Basic Systems evolved: The Stockholm System The Paris System The Manchester System Most systems used throughout the world are derived from these three basic systems
Stockholm/Paris System- Applications reported interms of “mg.h”( milligram hours)- product of totalmass of Radium contained in the sources (in mg) andduration of the application (in hours).Manchester System: Designed to deliver a constant doserate to defined points near cervix, irrespective of variationin size and shape of uterus/vagina.Application specified in terms of “dose” in Roentgens deliveredat specific points( Point A, Point B, Bladder Point, Rectal Point).Duration of implant based on the dose rate calculated at Point A.Optimal dose taken as 8000 R (72.8 Gy) in two sessions of 72 hrs. each, 4-7 daysinterval.
POINT A: Originally defined as 2 cm superior tothe lateral vaginal fornix and 2 cm lateral to thecervical canal( later redefined as 2 cm superior tothe ext cervical os/cervical end of the tandem,and 2 cm lateral to the cervical canal).POINT B: Defined 3 cm lateral to Point A( intendedto quantify the dose delivered to the Obturator L.Ns.)Dose to Bladder and Rectum: Localization ofbladder and rectum can be performed using radiographstaken with contrast media in bladder/rectum.Maximum dose to bladder/rectum: 80% or less thanthe dose to point A.
MANCHESTER SYSTEM APPLICATORS: Two vaginal Ovoids- made of hard rubber Locked in position by spacer or a washer Ovoid Sizes: 2.0/2.5/3.0 cm Intrauterine Tubes- made of thin rubber Three different lengths for 1/2/3 radium tubes each about 2 cm long. Each tube is closed at one end and has a flange at the other.
Manchester System: Definition of Points “A” and “B”
Manchester ovoid dimensions and applicator loadings were designed to ensure a dose rate of about 0.52 Gy/hr , which remained constant for all allowed applicator loadings and combinations. Vaginal contribution to point A was limited to 40% of the total dose. Current Practice- Point A dose is used to denote the average or minimum dose to the tumor.
Modern Fletcher-Suit Applicator Systems Adhered to the basic Manchester design. After loading capability was added to the Fletcher applicator by Suit and co-workers. Because of the similarity of Fletcher loadings to the Manchester loadings, Point A dose rates are nearly independent of the applicator dimensions. Use of Cs-137 instead of radium.
VAGINAL CYLINDER Used in conjunction with an Intrauterine tandem to irradiate the vagina when the disease extends from the uterine cervix along the vaginal walls. Cylinder can be used alone after a radical hysterectomy if there is a close or positive vaginal margin. Also useful for a patient with a very narrow vagina. Available in various diameters(1-5 cm) and lengths to fit any vaginal width or length.
CESIUM- 137 Most LDR intracavitary systems use Cesium as the implanted radioisotope. Similar in size and shape and have an output similar to radium sources. Elimination of Radon gas leakage. Less required shielding for radiation protection (lower energy, 0.662 Mev)
Characteristics of good insertion in brachytherapyA-P View:1) Tandem midline, unrotated2) Tandem midway between colpostats3) Colpostats high in the fornices along cervix (approx 1/3rd of the ovoid should be superior to the cervical collar and two-thirds should be inferior.Lateral View:1) Tandem bisects the colpostats2) Sufficient anterior and posterior packing3) Foley baloon firmly tugged down
SIMULATION:After insertion of the applicator, dummy sourcesare loaded into the afterloading applicators andan orthogonal pair of radiographs are taken.The isocenter is set at the centre of the collar for Fletcher-Suit tandem and ovoid applications.ICRU BLADDER and RECTAL REF POINTS:Bladder Point- Foley balloon is filled with 7 cc ofradiopaque fluid( Hypaque) and pulled down towardsthe bladder neck. On Lat radiograph, obtained by drawing aline through the center of the balloon and the posterior surfaceof the balloon is used as the reference point.On the anterior radiograph, the ref point is taken at centre of the balloon.
Rectal Ref Point: Lat radiograph- An AP line drawn from the lower end of the IU sources( or from the middle of the IV sources). The Rectal point is taken at a depth of 0.5 cm, posterior to the point where this line traverses the posterior vaginal wall( identified by intravaginal radiopaque gauge. AP radiograph- the Rectal point is at the lower end of the IU source or at the middle of thr IV sources at the midline.
Advantages of HDR versus LDR :1. Eliminates radiation exposure hazard for caregivers and visitors.2. Allows shorter treatment times.3. Less risk of applicator movement during therapy.4. Allows greater displacement of nearby normal tissues.5. Possible to treat larger no. of patients.
6. Allows use of smaller diameter sources than are used in LDR7. Reduces the need for dilatation of cervix and therefore, reduces the need for heavy sedation or GA every time.8. Physically easier to insert applicator into the cervix.9. Makes treatment-dose-distribution optimization possible.
HDR Equipment: Source most commonly used: Ir-192 Half life- 74 days An encapsulated Ir-192 source is attached to the end of a cable, which can be advanced or retracted in precise increments using stepper motors( stepping source). The ability to control the locations and dwell times permits greater flexibility modifying the d ds.
The Ring Applicator: Particularly useful when the vaginal fornices are asymmetric or absent. It is popular because it has a reproducible geometry and is easy to insert. It is important that the plastic cap of the ring applicator be in place with each insertion, because excessive vagina mucosal doses would be delivered without them. Also important not to activate the entire ring circumference; usually the lateral 4 – 6 dwell positions are activated on each side of the ring, dependent on the ring diameter.
SEQUELAE OF RADIATION THERAPYAcute: Diarrhea, abdominal cramping, rectal discomfort, Occasionally, rectal bleeding. Dysuria, frequency, nocturia, rarely hematuria; UTIs . Erythema, dry/moist desquamation in perineum or intergluteal fold. Radiation vaginitis/superficial ulceration of vagina/ vaginal stenosis
Follow-upEvery month- For first 3 months.Every 3 months- For remaining of the first year.Every 4 months- The 2nd year.Every 6 months- During the 3rd through 5th year.And yearly thereafter.Patients undergo Complete physical+ pelvic/rectal examination with Pap smear taken from 3 months onwards.(+ chest X-ray annually; CBC, Urea/creat. 6 monthly) Other investigations( USG/CT) as clinically indicated.