Radiotherapy In Gynaecology Prof. M.C.Bansal MBBS., MS., FICOG., MICOG. Founder Principal & Controller, Jhalawar Medical College & Hospital Jjalawar. MGMC & Hospital , sitapura ., Jaipur
RADIOTHERAPY IN GYNAECOLOGY Introduction Radiotherapy plays a major role in the treatment of patients with Gynaecological malignancies. Computer technology and information system have transformed many aspects of radiotherapy practices in last two decades. Three dimensional treatment planning based on computed tomography (CT)and MRI, optimized inverse planning , computer controlled treatment delivery and remote after loading Brachytherapy.
RADIOTHERAPY IN GYNAECOLOGY Introduction(contd) these techniques enable radiation oncologists to restrict radiation dose distribution to specified target volumes . Maximal dose is delivered to tumor ,while normal tissue is spared as much as possible. In1999 –2000 , results of randomized clinical trials demonstrated a significant improvement in pelvic disease control and survival when concurrent chemotherapy was added to radiotherapy for patients with locally advanced cervical cancer..
RADIOTHERAPY IN GYNAECOLOGY Radiation Biology Cellular effects of ionizing 1. Cellular death defined as the loss of clonogenic capacity e.g. inability to reproduce because of mitotic cell death. 2. Ionizing radiation may also cause programmed cell death (apoptosis) 3. The critical target for most radiation induced cell death is the DNA within the cells nucleus - Photons or charged particles inter act with intra cellular water to produce free radicals . Free radicals interact with DNA causing Breakage –Inability to reproduce. 4. Such Reproductive cell death may not be expressed morphologically until days and months . Some cells may still continue to divide before they die. 5. Apoptosis ( programmed cell death) may also play an important role in radiation induced cell death. The plasma membrane and nuclear DNA may both be important targets for this type of death.
RADIOTHERAPY IN GYNAECOLOGY Fractination Conventional radiotherapy is usually given in a fractionated course with daily doses of 180-200 cGy ( centi Gray) The difference between the Fractionation sensitivity of tumors and normal cells is an important determinant of the theraputic ratio of fractionated irradiation.
RADIOTHERAPY IN GYNAECOLOGY Dose Rate Effect As dose rate is decreased , tissue have more chance to tolerate the insult and repair from sublethal injury during therapy. This is called the Dose rate effect.
RADIOTHERAPY IN GYNAECOLOGY The four R’S The biological effect of a given dose of radiation is influenced by the Dose, Fraction size, Inter fraction interval and time over which the dose is given. Four R’s of radio-biology 1. Repair. 2.Repopulation 3.Redistribution. 4.Reoxygenation. These Four govern the influence of dose ,time and fractionation on the cellular response to radiation.
RADIOTHERAPY IN GYNAECOLOGY Repair Fraction irradiation permits greater recovery of sublethal injury during treatment , a higher dose of radiation is needed , to achieve a required biological effect when total dose is divided in to smaller fractions. Altered fractionation protocols usually require a minimum interval of 4- 6 hours between treatment
RADIOTHERAPY IN GYNAECOLOGY Repopulation Repopulation refers to the cell proliferation during the delivery of radiation. The magnitude of the effect of repopulation on the dose required to produce cell death depends upon the doubling time of the cells involved. For cells with a relatively short doubling time ,a significant increase may be required to compensate for a protraction in the delivery time.
RADIOTHERAPY IN GYNAECOLOGY Repopulation The speed of repopulation of normal tissue that manifest radiation injury soon after exposure (skin, mucosal surfaces etc). Treatments including chemotherapy, radiotherapy, surgery = its tissue response is lethal as well as an increase in proliferation of surviving cells(clonogens). This accelerated repopulation may increase the detrimental effect of treatment delays. It may influence the effectiveness of sequential multimodality treatments
RADIOTHERAPY IN GYNAECOL0GY Redistribution Study of synchronized cell population have shown differences in the radio sensitivity of cells in different phases of cell cycle. Cells are most sensitive in the late G1 phase and during mitosis . More resistant in mid to late S and early G1 phases. When synchronous dividing cells receive a fractionated dose of radiation , the first fraction tends to synchronize the cells by killing off those cells who are in most sensitive phase. Cells those in phase S begin to progress to more sensitive phase. during the interval between two fraction delivery. This phenomenon gives overall increased cellular death if cells have short cell cycle.
RADIOTHERAPY IN GYNAECOLOGY Re oxygenation The sensitivity of fully oxygenated cells to sparsely ionizing radiation is approximately 3 times more than anoxic cells. O2 is most effective radiation sensitizer. It is believed that O2 stabilizes the reactive free radicals produced by ionization.
RADIOTHERAPY IN GYNAECOLOGY Over coming Radio resistance Many treatment strategies have been explored to overcome the relative radio resistance of hypoxic cells in human solid tumor. 1. Hyperbaric oxygen or carbogen breathing 2. Red cell transfusion or growth factor. 3. Pharmacological agents e.g. Metronidazole , it acts as hypoxic cell sensitizer. 4. High linear –energy transfer radiation. tumor hypoxia continues to be one probable cause of the failure of irradiation.
RADIOTHERAPY IN GYNAECOLOGY Linear Energy Transfer & Relative Biological Effectiveness The rate of deposition of energy along the path of radiation beam is called Linear energy Transfer . Photons, high energy electrons, protons produce sparsely ionizing radiation beam of low energy transfer. Larger atomic particles e.g. neutrons and alpha produce much more densely ionizing beam with high linear energy transfer.
RADIOTHERAPY IN GYNAECOLOGY High linear transfer beam The high linear energy transfer beam: 1.There is a little or no repairable injury to tumor cells. 2.The magnitude of cell death from a given dose is greater. 3.The oxygen enhancement ratio is diminished. the high linear transfer beam’s use in the treatment of gynaeclogical malignancies had no major impact in producing results.
RADIOTHERAPY IN GYNAECOLOGY Hyperthermia Temperature is another factor which may modify the effect of radiation. Temperature in the range of 42-43 degree centigrade sensitize cells to radiation. This approach has given encouraging results but technical problems still limit its wide use.
RADIOTHERAPY IN GYNAECOLOGY Interaction between Radiation & Drugs Drugs and radiation interact in many different ways and modify cellular response. Steel & Packham categorize these interaction in Four groups 1.Spatial cooperation- Drugs and radiation act independently at different target and with different mechanism so that total effect is equal to the sum of effects of individuals . 2.Addivity—when two agents act on same target to cause damage – equal to sum of their individual toxic effect.
RADIOTHERAPY IN GYNAECOLOGY Interaction Between Radiation & Drugs3. Supra additivity—The drug potentiates the effect of radiation , causing a greater response than expected from simple additivity.4. Sub additivity—The amount of cell death is less from use of two agents simultaneously.
RADIOTHERAPY IN GYNAECOLOGY Therapeutic Ratio The difference between tumor control and normal tissue complications is referred to as Therapeutic Gain? Therapeutic Ratio. Primary aim of research in radiotherapy is to improve therapeutic ratio by increasing separation between these dose response curves, maximizing the probability of complication free tumor control.
RADIOTHERAPY IN GYNAECOLOGY Effects of Radiation on Normal Tissue Effect of radiation on normal tissue depends upon many factors :- 1. Radiation dose, the target organ, volume of tissue irradiated and division rate of irradiated cells. 2. Tissue that have rapid cell turnover (e.g. tissue which require constant cell removal like skin , mucosal epithelium , hair , bone marrow , reproductive tissue etc) tend to manifest radiation injury soon after irradiation. 3. Tissues whose functional activity does not require constant cell removal tend to manifest radiation injury late after months/years. Examples of late reacting tissues are connective , muscle and neural tissue. Some normal tissue may die through mechanism of apoptosis e.g. lymphocytes , salivary gland cells and intestinal crypt cells.
RADIOTHERAPY IN GYNAECOLOGY Effect of Radiation on Normal Tissue Acute Reaction Acute reaction to pelvic radiation , such as diarrhea is associated with mucosal denudation .The severity of acute reaction depends upon nature and volume of normal tissue , dose of radiation , interval between two fractions . Late Reaction It results from 1. Damage to vascular Struma that causes an epithelial proliferation with decreased blood supply and subsequent fibrosis. 2.Damage to slowly or in frequently proliferating paranchymal stem cells it eventually results in loss of functional capacity.
RADIOTHERAPY IN GYNAECOLOGY Effect of Radiation on Normal Tissue For a given dose of radiation administered over a given time interval , Risk of late effects is more with larger fraction. 1. Uterus and cervix are typically described as radio resistant except their mucosal linings. 2. Ovary is highly sensitive , it may lead to iatrogenic ovarian failure which is dose dependent as well as modulated by age of patient. Pre-menarcheal girls exposed to 30 Gy dose may continue to have mansturation and even may carry pregnancy to term . Although they experience premature ovarian failure later. Most adult women develop premature failure after 20 Gy.
RADIOTHERAPY IN GYNAECOLOGY Effect Of Radiation On Normal Tissue3. Vagina-- the Radiation tolerance varies with site , duration as well as radiation dose. Apical vagina require higher dose for atrophic changes , shortening and loss of its elasticity as compared to other areas.4.Vulva can withstand some Radiation similar to skin.
RADIOTHERAPY IN GYNAECOLOGY Effect Of RadiationORGAN Tolerance Dose Risk dose / serious side effects1.Small intestine 30Gy Diarrhea , Chronic Obstruction2.Rectum 45-50 Gy Bleeding , fistula , obstruction . Risk of stricture .3.Ureter 85-90 Gy4.Kidneys 18-22 Gy to both Renal hypertension & failure4.Liver 30 Gy Hepatic dysfunction5.Spinal cord & Nerves <50 Gy Uncommon 50 - 60 Gy Caudal equina6.Bone <10 Gy Bone marrow resting tissue fails to repopulate 30-40 Gy Aplastic anaemia , pathological
RADIOTHERAPY IN GYNAECOLOGY Treatment Strategies1.Hyper fractionation Dose per fraction is reduced , number of fractions and total dose is increased , but total time of treatment remains unchanged. Treatment is usually given 2-3 times per day at the interval of 6-8 hrs2.Accelerated Fractionation Dose per fraction is unchanged , over all duration of radiation is reduced , total dose is reduced or remain unchanged . It does not reduce the incidence of late effects but increases the acute effect of treatment.3.Hypofractionation usually avoided . Necessary reduction in dose reduces the likelihood of complete eradication of tumor with in the treatment field. Rx of malignant Melanoma is treated by this strategy , HDR brachytherapy used to achieve it.
RADIOTHERAPY IN GYNAECOLOGYCombination Of Surgery and Radiotherapy Because both are effective treatment . Surgery removes bulky tumor that may be difficult to control with tolerable dose of radiation. Combined radiation will sterilize the tumor bed and regional /distant Lymph Nodes. 1. Pre operative irradiation 2. Surgical staging followed by definite irradiation. 3. Intra operative irradiation. 4. Surgical resection following Post operative irradiation 5. Combination of these approaches.
RADIOTHERAPY IN GYNAECOLOGY 1. Preoperative Irradiation It is used to make the inoperable tumor – operable , example Ovarian Tumor , II stage Endometrial Cancer , bulky Ca Cervix . The greatest risk of this approach is that if tumor remains un resectable , the effect of further irradiation will be markedly decreased by increased interval between two treatment plans.
RADIOTHERAPY IN GYNAECOLOGY 2. Intraoperative In some cases intra operative irradiation can be delivered with a permanent implant (using 125 I or 198 Au )with after loading catheters in the operative bed or by ortho voltage unit in OT.
RADIOTHERAPY IN GYNAECOLOGY 3. Post Operative Irradiation It has been demonstrated to improve local, regional control. In Vulva cancer ,post operative pelvic and groin irradiation reduces the risk of recurrence and improves patient’s survival. Same is true for Ca Cervix and Endometrium With +ve lymph nodes.
RADIOTHERAPY IN GYNAECOLOGY Combination Approaches Combined therapy is optimized when treatment plan exploits the complimentary advantages of both treatment. It carries higher degree of morbidity. It should be limited to situation in which combined approach is likely to improve survival ,permit organ preservation, significantly less risk of local recurrence compared to the expected result from either modality alone.
RADIOTHERAPY IN GYNAECOLOGY Physical PrinciplesIonizing radiation lies in the high energy portion of the electromagnetic spectrum .Characterized by their ability to excite or ionize the atoms in absorbing material.The Nuclear decay of radioactive nuclei can produce several types of radiations , including uncharged Gamma(Y) rays , negatively charged beta rays (B) electrons , Positively charged alpha (a) particles (Helium ions) and neutrons .The resulting ionizing radiations are exploited therapeutically in Brachytherapy( using 226 Ra ,137 Cs 186 Ir and other isotopes ) .To produce Teletherapy Beams (e.g. 60 Co )The average energy of the photons produced by the decaying radioactive Cobalt is 1.2 million electron Volts (Me V) .
RADIOTHERAPY IN GYNAECOLOGY Interaction of Radiation & Matter X Rays and Y rays Photons interact with matter by means of three distinct mechanisms : Photoelectric effect , compton scatter,and pair production. Photo electric effect is used for diagnostic purpose--X rays having different absorbability by different tissue. Effect is proportional to Z3 . Z is the atomic number of the absorbing material. Modern therapeutic beams of 1-20 mega volts produce photons that interact with tissue primarily by compton scatter.indepedant of Z . These photons produce an increasing number of electrons and ionization as they penetrate beneath the surface of absorbing material. Skin sparing effects and penetration of energy beams of 15 MeV or greater make them useful in pelvic treatment. Pair production is related to Z2. this type of absorption begins to dominate only at photon energies of more than 30 MeV . It is of limited value in current radiation therapy planning.
RADIOTHERAPY IN GYNAECOLOGY Electron and other Particles Several types of particle beams are used in radiation therapy: electron beam, proton beam and neutron beams. Electrons are very light particles . When they interact with matter ,they loose their energy in a single interaction. Hence used to treat superficial targets without delivering significant dose to underlying tissue. Protons are +vely charged particles ,much heavier than electrons. Neutrons are neutral particles that tend to deposit most of their energy in a single intranuclear event. They are not used in gynaecology.
RADIOTHERAPY IN GYNAECOLOGY Measure of Absorbed Dose Absorbed dose is a measure of energy deposited by the radiation source in the target material. Unit currently used to measure radiation dose is the Gray(Gy) ,equal to 1 Joule per Kg of absorbing material. 1Rad= 1cGy= 100 rads. Safe radiation depends upon precise calibration of radiation source activities and machine output. Periodic calibration of equipment and sources are vital part of quality assurance in any radiotherapy department.
Relationship between radiation dose and surviving fraction ofcells treated in vitro with radiation delivered in a single dose orin fractions. Top = Most tumors and acutely respondingnormal tissues. Bottom = Late-responding normal tissues. For most tumors and acutely responding normal tissues, thecellular response to single doses of radiation is described by acurve with a relatively shallow initial shoulder (Top, yellowline). Cellular survival curves for late-responding normaltissues (Bottom, yellow line) have a more pronouncedshoulder, suggesting that these cells have a greater capacity toaccumulate and repair sublethal radiation injury. When the total dose of radiation is delivered in several smallerfractions (Dose A [dose/fraction] = blue line, or a largerfraction Dose B [dose/fraction] = red line), the response toeach fraction is similar and the overall radiation survival curvereflects multiple repetitions of the initial portion of the single-dose survival curve. Note that the total dose required to kill a specific proportion ofthe cells decreases as the dose per fraction increases (red line).Arrows indicate the differential effects of relatively largeversus small fractions of radiation. The greater differential effects of fractionated irradiation onnormal tissues (Bottom) than on tumor (Top) reflect thegreater capacity of late-responding normal tissues toaccumulate and repair sublethal radiation injury.
RADIOTHERAPY IN GYNAECOLOGY Inverse Square Law The dose of radiation from a source to any point in space varies according to the inverse of square of the distance from the source to the point. This relationship is particularly important for brachy therapy applications because it result in rapid fall off of dose as distance from intracavitary or interstitial source is increased.
RADIOTHERAPY IN GYNAECOLOGY Radiation therapy is delivered in three ways :- 1.TeletherapyXrays are delivered from a source at distance from the body(external beam therapy) 2.BrachytherapyRadiation source are put within OR adjacent to the target to be irradiated.(intra cavitary/interstitial) 3.Radioactive Solution solution that contain isotopes ( radioactive colloidal gold or 32 P) are instilled in in peritoneal cavity to treat the intra peritoneal metastatic nodules
RADIOTHERAPY IN GYNAECOLOGY Teletherapy Several terms are used – Percentage depth dose – change in dose with depth along the central axis of radiation beam. D max—The maximum dose delivered to the treated tissue. Source to skin distance – distance between source of X rays to skin surface. Iso center— a point in patient which remain constant at a fixed distance from source even when source is rotated. Source to axis distance—distance between source to iso center. Iso dose curve—is a line or surface that connects the point of equal radiation dose.
RADIOTHERAPY IN GYNAECOLOGY Teletherapy Following factors influence the dose distribution in tissue from a single beam of photons-- 1.Energy of beam –Higher energy photon beams are more penetrating than the low energy beam. Higher energy beam have a larger buildup region resulting in relative sparing of skin surface. 2.Distance from source to tissue—as the distance of source to skin surface increases ,the percentage depth dose increases. 3.The size of radiation field–the percentage depth increases with the increasing radiation field size.
RADIOTHERAPY IN GYNAECOLOGY Teletherapy4.The patient’s contour and the angle of the beams incidence.5.The density of tissue in the largest volume.6.A variety of beam-shaping devices placed between source and patient alter shape or distribution of radiation dose. Most radiation therapy treatment combine two or more beams to create dose distribution designed to accomplish three aims (i)Maximize dose delivered to tissue (ii)To produce homogenous dose within the volume of tissue (iii)to minimize dose to healthy tissue.
RADIOTHERAPY IN GYNAECOLOGY Teletherapy Multiple fields may be used to focus the high dose region more closer to deep target volume. Multi leaf collimators are computer controlled that can form irregularly shaped fields , replacing hand loading devices. Recently attention has been focused on IMRT to optimize delivery of radiation from multiple beam angles. The leaves of multi leaf collimators enter the field or retract dynamically to deliver desired dose of radiation to the tissue within target.
RADIOTHERAPY IN GYNAECOLOGY Brachy Therapy It involves placement of radioactive source within the existing body cavity.Termed as intra cavitary treatment . Most gynaecologic applications of intra cavitary therapy involves intrauterine/intra vaginal applicators that are subsequently loaded with encapsulated radioactive sources. These applicators are consisting of hollow tube /tandem and intra vaginal ovoids /receptacles. This technique has proven very useful in treatment of cervical cancer as it allows a very high dose of radiation to cervical , parametrial tissue & pelvic lymph nodes with out excessive radiation to surrounding normal tissue. To minimize the exposure to medical personnel ,modern applicators are first placed ,their position is checked with x rays and then applicator system is loaded. Remote after loading devices are used to automatically retract sources from the applicator to a lead lined safe when some one enters the room.
RADIOTHERAPY IN GYNAECOLOGY Isotopes Used in Gynaecological TreatmentElement Isotope Half life Ey (MeV) Eb (MeV)Phosphorus 32P 14.3 days None 1.7( max)Iodine 125I 60.2 days 0.028 avg None 131I 8.06 days 0.08-0.63 0.61(max)Cesium 137 Cs 30 yrs 0.662 0.514,1.17Iridium 192 Ir 74 days 0.32-0.61 0.24,0.67Gold 198Au 2.7 Days 0.41-1.1 0.96(max)Radium 229Ra 1,620 yrs 0.19-0.6 3.6(max)Cobalt 60 Co 5.26 yrs 1.17-1.33 0.313(max) E y, gamma ray energy Eb MeV beta ray energy Million Electron Volts
RADIOTHERAPY IN GYNAECOLOGY Dose Rate Historically, most brachy therapy was delivered at low dose. Most commonly 40-60 cGy / hr The advent of computer controlled remote after loading has made it possible to deliver higher doses. HDR treatment is given as OPD procedure. In this technique a single very high activity source of 192 Ir is loaded in the intra cavitary applicators. An alternative to HDR therapy commonly used in Europe, has recently been replaced by Pulse Dose Rate (PDR) brachy therapy in USA. The total brachy therapy dose to point A must be reduced when converting from LDR to HDR.
RADIOTHERAPY IN GYNAECOLOGY Dose rate If the tumor is very large or vaginal anatomy is unfavorable, radiation doses to tumor and normal tissue may be same. Dose fraction schemes used for HDR therapy produce tumor control and complication rates equivalent to LDR. Increasing the number of fractions and concomitantly decreasing the dose per fraction reduces rate of moderate and severe complications. Commonly used regimen in USA is % fraction of 5.5 -6 Gy each to point A , after 45 Gy to the pelvis with wide variation in fractions(2-13)and dose per fraction (3-9Gy).
RADIOTHERAPY IN GYNAECOLOGY Dose rate the appropriate dose and dose per fraction is based on calculation on estimated biologically effective dose (BED) on tumor and normal tissue. Bed= (nd)x (1+d/(a/b) where ,d is the dose per fractionFor example : Tumor BED = (30) x(1+6/10) = 48 GyNormal Tissue BED = (30)x( 1+6/3) = 90 Gy
RADIOTHERAPY IN GYNAECOLOGY Interstitial Therapy It refers to the placement of radioactive source with in the tissue. VARIOUS SOURCES OF RADIATION : Such as - 192Ir , 198Au , 125I , 103Pd , can be obtained as radioactive wires and seeds. Sources can be positioned in the tumor/tumor bed in variety of ways 1.Permanent seed implants (usually125I,103Pd,198Au) can be inserted using a specialized seed inserter. 2. Temporary Teflon catheter implants can be placed intra operatively and subsequently loaded with radioactive source.
Complications of radiotherapy Early Transient nausea and vomiting---- antiemetic drugs will help. Bladder and rectal irritation GIT irritation--. Anorexia , diarrhoea and weight loss. octreotide is used. Malaise, irrtability,depression and headache Flare up of sepsis pyometra,t.o.masses,peritonitis ansepticaemia. Cystiis, pyeliis, pyelonephritis. Pyerexia Pulmonary Embolism. Skin reaction
Late complications Persistant anaemia. Chronic pelvic pain followingfibrosis involving nerve trunks. Pyometra. Proctiis--.rectal ulcer,bleeding,strcture and rectovaginal fistula. Post radiation cystitis,ulcer,haemturea, UTI and vesicovaginal fistula. Smallbowel strictures ,ulcers, obstruction, gut perforation. Colonin- stricture,ulcer, telangiectasia,perforaton, obstructiontropic vagints, ca, stenosis, dyspreunia. Ureterc obstruction and obstructive uropathy. Osteporosis and fracture neck of femur. Overian dysfunction/failureUterine sarcoma 8% cases
Contra Indication To radiotherapy Sever anaemia. Poor general health. Sepsis. Pregnancy. Presence of fibroid in uerus. Tubo- ovarian masses. Utero vaginal prolapse. Fistulas. Radio resistant tumors
RADIOTHERAPY IN GYNAECOLOGY Interstitial Therapy 3.Temporary transperineal template guided interstitialneedle implants can be placed using a Lucite template withregularly placed holes and a central obturator that can holdtanden or additional needles. Needles are after loadedwith192 Ir. These implants are used to treat vaginal andsome cervical tumors 4.Temporary transperineal implants can also be placedfreehand an approach that may allow better control ofneedle placement in selected cases. Useful in treatingvaginal and urethral cancers. Most gynaecological implants are temporary LDRimplants like intracavitary therapy. Interstitial therapydelivers a relatively high dose of radiation to a small volumesparing the surrounding normal tissues. The risk to normaltissue adjacent to tumor or in the tumor bed still will besignificant, particularly when needle placement isinaccurate.
RADIOTHERAPY IN GYNAECOLOGY Intraperitoneal Radioisotopes Radioactive phosphate(32P) and colloidal gold(198Au) used for treatment of epithelial cancers of ovary in an effort to address the transperitoneal spread of cancer . If a radioisotope is evenly distributed within peritoneum , it is theoretically possible to irradiate the entire surface. However the energy deposition within the abdomen and the dose delivered beneath the peritoneal surface depends on many factors i.e. distribution of isotope and energy of decay product. In practice isotope is seldom distributed evenly in peritoneal cavity and omental surface. This approach is rarely used now a days.
Xray of pelvis showing position of radium in Manchestr insertion
RADIOTHERAPY IN GYNAECOLOGYClinical uses of radiation Cancer Cervix The curative treatment of cancer cervix usually includesexternal pelvic irradiation and brachy therapy often withconcurrent chemotherapy. The goal of therapy is to eliminate cancer in cervix paracervical tissues and regional lymph nodes. Because bulkiest tumor is usually in cervix, this regiontypically requires higher dose than the rest of pelvis toachieve loco regional control. Fortunately it is possible todeliver higher dose with intra cavitary therapy.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Treatment Volume : Typical external- beam fields are designed to include the primary tumor , para cervical iliac and pre sacral nodes ,all with 1.5- 2.5 cm margins. If common iliac and aortic nodes are involved, then the treatment fields are extended at least to lower para aortic region. The borders of field are as follows 1.Inferior - at the mid pelvis / 2-3 cm below cervical lesion. 2.Superior - at the L4-5 interface / bifurcation of aorta. 3.Lateral to pelvic lymph nodes 1-2cm / at east 1cm lateral to margin of bony pelvis.
Isodose curves of a standard radium insertion using the Manchester Technique in Ca Cx
Different methods of brachy therapy A.Manchester , B Paris , C. Stockholm.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Using four beams (anterior, posterior, right and left lateral)rather than opposed pair of anterior and posterior beams may some times reduce volume of tissues irradiated to a high dose. 4 to 5 weeks (40 - 45 Gy ) of radiation and combined chemotherapy usually reduces endo cervical disease and shrinks exophytic tumor , fascilitating optimal intra cavitary therapy. Intra cavitary therapy is critically important for successful treatment , even for patients with very bulky stage III tumors.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Patient with FIGO stage IA can often be treated with intracavitary irradiation alone. Most patients with stage IB1 have high risk of metastasis to pelvic lymph nodes , hence need atleast moderate dose of pelvic radiation (39.6Gy) to sterilize possible microscopic regional disease. For patient of Ca Cx having vaginal bleeding haemostasis can be achieved with vaginal packing ,application of Monsel’s solution and rapid initiation of External Beam Irradiation.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Radiation Dose-- 1.Point A – a point 2cm lateral and 2cm superior to external cervical os. 2.Point B - a point 3cm lateral to point A.The total dose to point A - from external beam and LDR intacavitary therapy adequate to achieve central disease control is between 75 Gy (for IB1 stage) & 90 Gy (for bulky or locally advanced disease).Prescribed dose to point B is 45-65Gy , depending on extent of parametrial and side wall disease.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Prescription and treatment planning can not be limited tospecification of the dose to these reference points . Other factors to beconsidered are as follows :— 1.The position and length of intrauterine tandem 2.The type and size of vaginal applicators. 3.Quality of vaginal packing. 4.The size of central tumor(before and after external beam therapy 5.The vaginal surface dose ( usually limited to 120 to 140 Gy). 6.Oroximity of system to bladder and rectum 7. The dose rate or fraction size.There is growing move toward use of image guided brachytherapy.Treatment planning based on CT / MRI images obtained withimplant in place.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Results of treatment : Radiation therapy is extremely effective in the treatmentof stage IB1 . Disease control achieved in central andpelvic lesion is greater than 98%and 95% respectively. Pelvic control rate decreases as tumor size and FIGO stageincreases. 5 year pelvic control rate of 50-60% even for bulkystage IIIB have been reported. During the past decade significant improvement in pelvicdisease and survival when Cis-platin containing chemotherapyis delivered concurrently with radiation to patients withadvanced pelvic lesions. 5 fluouracil a potent radiosensitizer is not that effective inRx of Ca Cx . Mitomycin C and Epirubicin given along withradiotherapy also help control advanced disease.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer CervixAdjuvant pelvic radiation after radical Hysterectomy. For patient with stage IB and IIA Ca Cx who had radical hysterectomy along with pelvic lymphadenectomy , involvement of nodes is strongest predictor of local recurrence and death. Survival rate of patients with +ve nodes is 50-60% much lower than that achieved by chemo- radiotherapy. Post operative radiotherapy is must for them. Patients with – ve nodes but bulky cervix > 4cm and deep stromal invasion also require post operative radiotherapy. Adjuvant radiotherapy carries high risk of complications and Patients who have high risk factors at initial evaluation should be treated by radical radio –chemotherapy.
RADIOTHERAPY IN GYNAECOLOGY Clinical uses of radiation Cancer Cervix Recurrent Cervical cancer Patient who have an isolated pelvic recurrence after radical hysterectomy can be treated by aggressive radiotherapy. Patients with local recurrence with no fixation to bone/+ve pelvic nodes have 5 year survival rate as 60-70-% Patient having +ve nodes/fixation to bone have very poor survival rate of 20% after radiotherapy.
Endo cervical Cancer 1.Chemotherapy. 2. Radiotherapy. 3. surgery all three are combined In endo cervcal cancer the best survival is seen whenconcomitant Cisplatin weekly and 6 weeklyradiotherapy is followed by surgery.
Endometrial cancer As adjuvant to surgery comprising : TAH-1-BSO By administrating vaginal radiation via colpostsat ,vaginal vault recurrence drops by 20%. To prevent local vaginal recurrence which is reported in 13 % The survival improves in stage 1C and II when post operative radiation is given to pelvic nodes. It is indicated in Sarcoma. To treat pt unfit for surgery. To treat pt with pelvic/ vaginal recurrence. For palliation in cases of non resectable intra pelvic / metastatic disease.s
Ovarian Cancer Post surgery and chemotherapy ; ― Moving Strip Technique ― of external radiation is applied to par aortic nodes and residual abdominal metastasis. In this a strip of 2.5b cm area is radiated front and back(starting from pelvis) over 2days and then moved upwards until whole abdomen and back is irradiated.Liver and Kidneys are shielded. The total tumor dose of 2600- 2800 cG y is administered. CT and MRI are use ful in detecting involved para aortic and pelvic metastasis.
Ovarian Cancer---------- Intra abdominal instillation of AU 198, P 34 and thiotepa is not used now a days owing to intestinal injury and adhesion formation. Approximately 49-50% 5 year survival rate can be achieved in stage II. 5 year survival rate drops to 5-15% if larger residual lesions are left after intial surgery combined with chemotherapy.
Vulvar Cancer The aim of integrated multimodality therapy including surgery, chemo radio therapy is to reduce the risk of local, regional failure in patients with advanced primary or distant nodal involvement. To obviate the need of exenteration in women having urethra , Anal extension of cancer. The dose of radiation given is 4500-5000cGy to woman with microscopic disease and 6000- 6400cGy to woman with macroscopic disease. Pre operative Radium needles (60 Gy in 6 days) shrinks the tumor and facilitates extirepation of tumor at later date . Post operative radiotherapy is prefered to women with +ve inguinal nodes.
Vaginal Cancer Radiotherapy is preferred then surgery. If cancer is located in upper 1/3rd ., it is radiated as ca Cx. If located in middle/ lower 1/3rd of vagina , interstitial needles (Iridium - 192) are inserted in vaginal tumor.
Chorio Carcinoma It respond well to chemotherapy which replaced surgery in young women. Radio therapy is applicable in the distal metastasis in few cases.