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  1. Radiotherapy Techniques In Carcinoma Cervix Presented by : Dr. Isha Jaiswal Guided by: Dr Ritusha Mishra Date: -5th May 2015
  2.  RT plays an important role in management  high dose can be delivered by combined technique of EBRT & Brachytherapy
  3. • The cervical cancer has two components • Central component – • disease confined to cervix , vagina & medial parametria • best treated by brachytherapy • Peripheral component – • disease involving lateral parametria & regional lymph nodes • best treated by EBRT& brachytherapy as boost
  4. External-beam pelvic irradiation is delivered before Intracavitary insertions in patients with • Bulky cervical lesions/tumors beyond stage IIA to improve the geometry of the intracavitary application; • Exophytic, easily bleeding tumors • Tumors with necrosis or infection • Parametrial involvement. Perez & Brady's Principles and Practice of Radiation Oncology;6thedition,pg 1373
  5. Indications of EBRT • As definitive RT • As adjuvant RT in post operative settings • As palliative RT
  6. Indication of definitive RT: may be considered in stages IA & CIS : * if pt. deemed inoperable or avoids surgery or RT preferred IAI:Brachytherapy alone IA2 or IA1 with LVSI:ICBT plus external beam radiotherapy * Stages IB-IIA if pt. deemed inoperable* or avoids surgery or RT preferred  EBRT and brachytherapy *Randomised study of radical surgery versus radiotherapy for stage Ib–IIa cervical cancer. Landoni F, Maneo A, Colombo A, et al Lancet 1997;350:535–540 Stages IIB to IVA:  EBRT + BT + concurrent chemo radiotherapy
  7. Indications Of Post-op EBRT1 any 2 of the following:  > 1/3rd Stromal Invasion LV space Invasion Large (>4 cm) tumor Indications Of Post-op CTRT2 Positive Pelvic Nodes microscopic positive/close (<3 mm) margins microscopic involvement of Parametrium 3Monk et al subgroup analysis showed that benefit was less in pts. with ≤2 cm tumours & only 1 node positive 2 1 3
  8. Indications of Palliative radiation • In stage IVB : • for indications such as • vaginal bleeding, • pain • urethral obstruction
  9. Paraaortic L.N irradiation: indications • Definitive: • in radiologically/histologically positive paraaortic L.N • Prophylactic: in pt. with high risk of paraaortic L.N involvement: pt with positive pelvic nodal ds and not receiving CTRT • Evidences:
  10. • Nov 1979-Oct 1986 • N=367;bulky IB-IIA & IIB disease • Clinically apparent or surgically involved para-aortic nodes excluded from study. • Pelvic only or pelvic+para-aortic RT without any chemotherapy • Pelvic irradiation consisted of 1.6-1.8 Gy/day for 5 days/week to total of 40-50 Gy. • Para-aortic irradiation delivered 44 to 45 Gy in 1.6-1.8 Gy/day, 5 days/week • A total dose of 4000 to 5000 mg/h of radium equivalent or 30 to 40 Gy was provided by intracavitary brachytherapy to point A.
  11. Results:10 yrs. • lower cumulative incidence for first distant failure in the pelvic plus para-aortic irradiation arm (P = .053). • Survival following first failure was significantly higher in the pelvic plus para-aortic arm (P = .007). • death rate due to radiotherapy complications was higher in the pelvic plus para-aortic arm (four [2%] of 170) compared with the pelvic only arm (one [1%] of 167) (P = .38). • proportion of deaths due to radiotherapy complications in the pelvic plus para-aortic arm was higher than in the pelvic only arm (four [6%] of 67 vs one [1%] of 85; P = .24). pelvic only irradiation arm pelvic plus para-aortic irradiation am P value 10 yr OS 44 % 55% P=.02 10 yr DFS 40% 42% NS LRF 35% 31% P=.44 grade 4 &5 toxicities 8% 4% P=.06
  12. CONCLUSIONS OF RTOG 79-20: • The statistically significant difference in overall survival at 10 years for the pelvic plus para-aortic irradiation arm, without a difference in disease-free survival, can be explained by the following two factors: • (1) a lower incidence of distant failure in complete responders • (2) a better salvage in the complete responders who later failed locally • A higher percentage of local failures were salvaged long-term on the pelvic plus para-aortic arm compared with the pelvic only arm (25% vs 8%).
  13. • 441 pts. • Randomized. Stage IB-IIB with positive pelvic LN; or Stage IIB with distal vaginal and/or parametrial involvement; or any Stage III. • Randomized to pelvic RT vs pelvic + PA RT (45 Gy). • no statistically significant difference between the two treatment arms in terms of • local control, • overall distant metastases • survival with no evidence of disease (NED), • although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone (pelvic group). • incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation (para-aortic group). • Conclusion: Routine PA RT is not indicated
  14. • N=403 • High-risk patients: IIB-IVA, positive pelvic nodes, bulky(≥ 5cm )IB-IIA • compared extended-field radiotherapy (EFRT) versus pelvic radiotherapy with concomitant fluorouracil and cisplatin (CTRT) • The EFRT arm was the control arm, established on the basis of the RTOG 79-20 trial • median follow-up time for 228 surviving patients was 6.6 years.
  15. overall survival rate for patients treated with CTRT was significantly greater than that for patients treated with EFRT (67% v 41% at 8 years; P <.0001). Patients with stage IB to IIB disease who received CTRT had better overall survival than those treated with EFRT (P <.0001);
  16. RESULTS: Pelviv CTRT was superior to EFRT in 8 yr OS 67% vs. 41% DFS: 61% vs 46% LRF:18 %vs 35% DM:20% vs 35% There was slight increase in PA nodal failure in CRT arm(8% vs. 4%;p=NS) The rate of serious late complications of treatment was similar for the two treatment arms. CONCLUSION: Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.
  17. EBRT: treat the whole pelvis (WPRT) Target volume includes uterus and cervix tumor bed, in postoperative cases vagina: depending on extent of involvement parametrial tissue lymph nodes. paracervical, parametrial,obturator,presacral L.N internal iliac, external iliac, common iliac L.N para-aortic L.N in selected cases(clinical or radiological positive)
  18. EBRT techniques • Conventional • 3DCRT • IMRT/IGRT
  19. Planning technique • Positioning & Immobilization • Simulation • Field design • Beam energy • Dose & fractionation
  20. Positioning & Immobilization Patients may be positioned in • Supine position • Prone position with belly board supine position is preferred because • Most comfortable • Reproducible position • Stabilizes pelvis • Can be combined with immobilization devices knee rest can be used • Relaxes lower back making pt. more comfortable • Minimize rotation of pelvis • Knee rest with indexing limits superior-inferior and lateral motion
  21. Prone position on a belly board Belly Board is used to allow the intestinal tract to drop out of treatment field. Made of foam material has a low absorption of the beam. In hysterectomy pts: • small bowel may drop into the pelvic area so prone position may be beneficial For patients with an intact cervix, the small bowel often lies superior to the uterus and above the pelvic brim, creating less need to shift the bowel out of the pelvis.
  22. Immobilization  Several types of immobilization options available in radiotherapy  Needs to be:  Comfortable  Reproducible  Minimal beam attenuating  Affordable
  23. Immobilization options  Thermoplastics form the basis for immobilization in head and neck  In the pelvis these are difficult to be used as:  Lack of bony points for fixation  Continuing abdominal movements with respiration  Presence of fat pads and folds  simple supine positioning with skin markings:  Cheap  Reproducible  Ease of use and comfortable for patient.
  24. Need of contrast during simulation • Usually not needed in CT simulation • because structures can be contoured even without contrast on CT. • May be helpful in conventional simulation to enhance the soft-tissue detail • contrast may be placed at following sites iv contrast to localize the pelvic vessels oral contrast to delineates small bowel. Foley’s catheter with bladder contrast barium in the rectum, vaginal tube in the vagina,
  25. X-Ray Simulation Conventional simulator can be used to acquire patient data  Patient position: supine with arms on the chest, knee and lower leg immobilisation or alpha cradles may be used to prevent pelvic rotation Orthogonal laser beams aligned with anterior and lateral tattoos marked with radio-opaque material. For obese patients, a prone belly board may be used to allow small bowel to fall anteriorly Inferior border of tumor marked with radio-opaque material. Bladder protocol is used to maintain a constant bladder filling – ‘comfortably full’  AP and lateral simulator films are taken.  Standard field borders decided using bony anatomical landmarks.
  26. Field borders: AP-PA fields Superior border • At the L4-5 space to include external & internal iliac L.N. • extended to the L3-4 space if common iliac nodal coverage is indicated • . extended to the T11-12 space if paraaortic coverage is indicated Inferior border • at inferior border of the obturator foramen. • For vaginal involvement:3cm below the lower most extent of disease Lateral borders • 1.5 - 2cm margin on the widest portion of pelvic brim • tumours that involve lower third of vagina, inguinal nodes should be included in the fields
  27. Field borders : lateral field Anterior margin • vertical line to the anterior edge of pubic symphysis to cover external iliac lymph nodes Posterior margin • at S2 – S3 junction • extend to sacral hollow in patients with advanced tumours to cover uterosacral ligaments, cardinal ligaments & presacral lymph nodes • Superior & inferior margins • same as that for AP/PA Fields
  28. Shielding of A-P fields • Individualised shielding is employed in the anterior beam to superior corners to exclude small bowel. • Shielding to the inferior corners to protect femoral heads may mask the external iliac nodes and should be used carefully. •Red: cervix; •Blue: uterus; •Green: bladder; •Brown: rectum •Orange: common illiac LNs; •Yellow: external illiac LNs; •Light Green: obturator LNs; •Purple: internal illiac LNs; •Dark Green: presacral LNs
  29. • Lateral beams have shielding to sacral nerve roots posteriorly. • For simulation of para-aortic nodal beams, intravenous contrast is required to localise kidneys for shielding Shielding of Lateral fields •Red: cervix; •Blue: uterus; •Khaki: bladder; •Brown: rectum •Orange: common illiac LNs; •Yellow: external illiac LNs; •Light Green: obturator LNs; •Purple: internal illiac LNs; •Dark Green: presacral LN
  30. Midline shielding • Depending on brachytherapy dose administered, midline shielding with rectangular or specially designed blocks has been traditionally use for a portion of EBRT dose delivered with the AP-PA ports • Midline blocks may be individualized, based on the point A isodose line or a rectangular block of approximately 4-cm width. • However, in the era of 3D brachytherapy planning, the use of a midline block has been questioned because it may result in tumor underdosing while still contributing significant dose to the bladder, sigmoid, and rectum Perez & Brady's Principles and Practice of Radiation Oncology,6th edition pg 1378
  31. PARAAROTIC L.N. IRRADIATION • Extended field RT: • pelvis & para-aortic L.N. should be treated as contiguous extended field portal • Separate field: • Para-aortic L.N. and the pelvis are irradiated through separate portals • In this case, a gap calculation b/w the pelvic and para-aortic portals must be done to avoid overlap and excessive dose to the small intestines.
  32. Extended field RT :Paraaortic L.N field border • superior border :covers renal hilum, often at T12-L1 interspace, • inferior borders :at L5-S1 when separate field or up to lower border of pelvic field in EFRT • anterior border :rests 2 cm in front of the vertebral body or enlarged nodes as contoured • posterior border: bisects mid-vertebral body. • Lateral border: width (in general, 8 to 10 cm) can be determined by CT scans, MRI, lymphangiography, FDG-PET scans, or IV pyelography outlining the ureters Extended field anteroposterior (AP) radiation portal covering the para-aortic nodes. Courtesy of Kristin Bradley, MD and Derek McHaffie, MD
  33. Para-aortic field: 2 field vs. 4 field • AP-PA treatments to the para-aortic nodal chain may overdose the kidneys, spinal cord, and small bowel. • The spinal cord dose (T12 to L2–3) should be kept to <45 Gy • This can be done by • interposing a 2-cm-wide 5–half-value-layer shield on the posterior portal (usually after 40-Gy tumor dose) • or using lateral ports and limiting the kidney dose to <18 Gy • The use of four fields, including AP-PA and two lateral fields, is implemented as an alternative to AP-PA alone as a way to reduce some of the dose to the anterior small bowel, kidney S.C
  34. Midline Shielding in AP-PA Portals and Use of a Parametrial Boost • for patients with persistent disease after approx. 45-50 Gy EBRT to pelvis midline shield can be used to boost parametria or nodes • When parametrial tumor persists, 50 to 60 Gy may be delivered to the parametria, with reduced AP-PA portals • In the modern era, the use of highly conformal boosts with 3D planning,IMRT & HDR 3D brachytherapy have replaced conventional technique • Also midline block may not be beneficial in patients receiving 3D image- planned brachytherapy with adequate optimization of dose to the tumor and away from the normal tissues. Midline block for Parametrial Boost Perez & Brady's Principles and Practice of Radiation Oncology,6th edition pg 1378
  35. Treatment technique: SSD Vs SAD • SSD treatments: • Setup possible without requiring expensive aids e.g. Laser • SAD treatments: • Ease of setup reproducibility • Impact of setup inaccuracies is minimized The principal advantage of isocentric technique over SSD technique is that the patient is not moved between fields. Once the isocenter is positioned accurately within the patient, the remaining fields are arranged simply by gantry rotation or couch movement, not by displacing the patient relative to the couch.
  36. TWO FIELD • Heterogeneous dose distribution • Parametrium under dosed • More skin reaction • Useful when lower part of vagina involved FOUR FIELD • Homogeneous box shaped dose distribution • Whole target vol. including parametrium gets adequate dose • Skin reaction are decreased • Treatment time more
  37. Dose distribution -2 field vs. 4 field
  38. BEAM ENERGY • Because of the thickness of the pelvis, high-energy photon beams (10 MV or higher) are especially suited for this treatment. • They decrease the dose of radiation delivered to the peripheral normal tissues (particularly bladder and rectum) • provide a more homogeneous dose distribution in the central pelvis. • avoid subcutaneous fibrosis
  39. Dose & fractionation Primary radiotherapy Stage IB2 and IIA • 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks followed by Intracavitary brachytherapy. Stage IIB or above • 50.4 Gy in 28 daily fractions of 1.8 Gy given in 51⁄2 weeks followed by Intracavitary brachytherapy. Persistant /bulky parametrial tumor: boost upto 60 Gy Adjuvant radiotherapy • 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks. • 50.4 Gy in 28 daily fractions of 1.8 Gy in 51⁄2 weeks if macroscopic residual disease. Para-aortic node radiotherapy • Adjuvant radiotherapy:45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks. Palliative treatment • Whole pelvis or para-aortic nodes • 20–30 Gy in 5–10 daily fractions given in 1–2 weeks. • 8–10 Gy in 1 fraction for haemostasis. Practical Radiotherapy Planning; Jane Dobbs;pg 392
  40. Is the X-ray planned 4 field box still acceptable EBRT? • Majority of failures are marginal. • Usually immediately superior to the radiation field. • These recurrences suggest a deficiency in target volume • There is significant geographic miss superiorly (common iliac nodes) and laterally (external iliac nodes • This correlates with the sites of intra-pelvic failures.
  41. Dosimetric comparison between conventional and conformal radiotherapy for carcinoma cervix • Three-dimensional conformal radiotherapy gives significantly better target coverage, which may translate into better local control and survival. • On the other hand, it also requires significantly larger field sizes though doses to the OARs are not significantly increased.
  42. Aims: To estimate inadequacies in target volume coverage when using conventional planning based on bony landmarks. Materials and Methods: 50 patients. biopsy-proven patients of locally advanced uterine cervix cancer stage II-III 32 patients (64%) belonged to Stage IIB and 18 (36%) to Stage IIIB. All patients were planned for radical radiation of 46Gy/23 fractions over 4.5 weeks and 78% patients received concomitant chemotherapy with weekly cisplatin at a dose of 40 mg/m2 followed by two sessions of HDR intracavitary brachytherapy, with a dose of 9 Gy per fraction. In all patients, the treatment was completed within 56 days of starting external radiation
  43. Dosimetric study of target volume coverage of the treatment plans were done Target volume delineation was done on planning CT scans using Taylor et al and Small et al contouring guidelines The target volume delineated was then projected onto the digitally reconstructed radiograph (DRR) and the distance of the target volume from the edges of the field was measured using the Beam’s Eye View The volume of the target receiving at least 95% of the prescribed dose was calculated (V95). V95 was subtracted from the total target volume to calculate the volume that would have been missed in conventional planning based on bony landmarks
  44. Results: In 48 out of 50 patients, the conventional four field box failed to encompass the target volume. areas of miss were at the superior and lateral borders of the anterior-posterior fields, and the anterior border of the lateral fields.
  45.  there was a statistically significant increase in volume of tissue irradiated while using CT-based 3-D plans  In addition, the mean dose to the bowel and bone marrow was increased significantly in the CT-based plan when compared with four field plan Comparison of few dosimetric parameters between the two plans Conclusions: study shows inadequate target volume coverage with conventional four field box technique. It recommend routine use of CT-based planning for treatment with radiotherapy in carcinoma cervix
  46. 3D CRT Planning • Patient position and immobilization • Volumetric data acquisition • Image transfer to the TPS • Target volume delineation • Planning • Dose distribution analysis • Treatment QA & delivery
  47. CT SIMULATION  CT scanning is recommended for data acquisition.  Patients are usually scanned in supine position, arms overhead , knees immobilised with knee rest  For obese pts. prone belly board may be used  A vaginal marker is placed at the lower extent of disease when it extends into vagina to determine the length of vagina involved  Or the marker can also be placed at the external os and the lower extent of disease individually determined based on findings of clinical examinations  Intravenous contrast is used to outline pelvic blood vessels to be used as surrogates for pelvic node  Oral and rectal contrast may be given for delineation of critical structures  CT scan is obtained from T10-T11 interspace to upper third of femur,  slice thickness may vary from 3-5 mm depending upon institutional protocol  These images are transferred to treatment planning system (TPS) and contouring is done
  48.  In pelvic malignancies bladder filling status has largely been the matter of debate.  George et al.,[1] and Pinkawa et al.,[2] recommended a full bladder for treatment of gynecological malignancies, as the dose-volume-load to bladder and cranially displaced sigmoid colon/small bowel loops can be reduced significantly.  However; Pinkawa in another study[3] found that bladder wall displacements are reduced significantly (P < 0.01) at superior and anterior border while treating empty bladder compared to full bladder and also there is less variability in bladder volume in an empty bladder state.  the ideal bladder filling status has not been ensured by any study so far.  The bladder protocols may vary from institution however most institute follow a consistent bladder filling protocol of voiding urine 15 min prior to both imaging and treatment Bladder Protocol for Simulation 1:Georg P, Georg D,et al. Factors influencing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies. Radiother Oncol 2006;80:19-26. 2:Pinkawa Met al. Dose-volume histogram evaluation of prone and supine patient position in external beam radiotherapy for cervical and endometrial cancer. Radiother Oncol 2003;69:99-105. 3.:Pinkawa M,, et al. Bladder extension variability during pelvic external beam radiotherapy with a full or empty bladder. Radiother Oncol 2007;83:163-7.
  49. Target Volume delineation  For definitive treatment of carcinoma cervix with conformal radiation techniques, accurate target delineation is vitally important,  Various guidelines for CTV delineation are published in the literature yet a consensus definition of clinical target volume (CTV) remains variable  Clinical judgement remains the most important aspect of determining the target volumes
  50. Contouring Several contouring guidelines available for CTV Taylor et al pelvic nodal delineation (CT based) Toita et al for CTV delineation in intact cervix EBRT (CT based) Lim et al for CTV delineation in intact cervix IMRT (MRI based) Small et al for CTV delineation in post operative IMRT (CT based) PGI literature review & guidelines for delineation of CTV for intact carcinoma cervix (CT based) Guidelines for organ at risk Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas (CT based)
  51. Components of CTV The group consensus was that entire uterus should be included in the CTV because: • Uterus & cervix are embryologically one unit with interconnected lymphatics and no clear separating fascial plane • Second, determination of myometrial invasion can be difficult • uterine recurrences have been reported (2%), but exact location of these recurrences(fundal vs. corpus) have not been stated
  52. Parametrial contouring guidelines
  53. superior boundaries of parametria are at the top of the fallopian tube, and contours should stop once loops of bowel are seen next to the uterus as this is clearly above the broad ligament For the very anteverted uterus, particularly where the fundus lies below the cervix, the parametrial volume should stop once the cervix is seen Inferiorly, the parametrial tissue finish at the muscles of the pelvic floor
  54. Anteriorly boundary lies at the posterior wall of the bladder Bladder or In patients with a very small bladder (which lies deep in the pelvis), posterior border of the external iliac vessel Posteriorly: bounded by the mesorectal fascia and uterosacral ligaments parametrial volumes would extend up to the rectal contour in advances stages Laterally, the parametrial volume should extend to the pelvic sidewall (excluding bone and muscle). some overlap of this volume with nodal CTV, particularly along the obturator strip
  55. Taylor A, Rockall A, Powell M. An Atlas of the Pelvic Lymph Node Regions to Aid Radiotherapy Target Volume Definition. Clinical Oncology. 2007 Sep ;19(7):542-550.
  56.  External iliac :7 mm margin around vessels.  Extend anterior border by a further 10 mm anterolaterally along the iliopsoas muscle to include the lateral external iliac nodes  Internal iliac: 7 mm margin around vessels. Extend lateral borders to pelvic side wall
  57. lateral external iliac nodes (blue),  inguino-femoral nodes (green)  parametria and upper vagina (red). pre-sacral (PS), internal iliac (II), obturator (Obt), lateral (EIl), medial(EIm) and anterior (EIa) external iliac,  parametrial and paravaginal (Pm),
  58. CTV definition for the post-operative therapy of endometrial and cervical cancernshould include the common, external, and internal iliac lymph node regions. The upper 3.0 cm of vagina and paravaginal soft tissue lateral to the vagina should also be included. For patients with cervical cancer, or endometrial cancer with cervical stromal invasion, it is also recommended that the CTV include the presacral lymph node-region
  59. • Upper Common Iliac CTV • Mid CI (red) , Pre-sacral CTV (blue) • Lower C.I (red) ,Pre-sacral CTV (blue) • Upper El and II (red) PS blue • Parametrial/Vaginal (green) CTV Vaginal CTV
  60.  The aim of the article was to review the guidelines for CTV delineation published in the literature and to present the guidelines practiced at their institute  6 articles : 2 articles from Taylor et al and Toita et al and 1 from Small et al., Lim et al., were reviewed  The CTV in cervical cancer consists of the CTV nodal and CTV primary.  CTV nodal consists of common iliac, external iliac, internal iliac, pre-sacral and obturator  group of lymph nodes, and CTV primary consists of the gross tumor volume, uterine cervix, uterine corpus, parametrium, upper third of vagina and uterosacral ligaments.  Pelvic LN CTV is contoured in accordance with the latest Taylor’s guidelines with some modifications  This was the first report to provide the complete set of guidelines for delineating both the CTV primary and CTV nodal in combination
  61. Normal Tissue Delineation (RTOG) • Bowel: The small and large bowel can be contoured together as a Bowel-Bag. • Inferiorly, the bowel bag should begin with the first small or large bowel loop or above the ano-rectum, whichever is most inferior. • The contours should end 1 cm. above the PTV . • Ano-Rectum: Ano-Rectum should be contoured from the level of the anus to the sigmoid flexure. It should extend from the anal verge (marked by a radiopaque marker at simulation) to superiorly where it loses its round shape in the axial plane and connects anteriorly with the sigmoid. • Bladder: Contoured inferiorly from its base, and superiorly to the dome. • Femoral Heads:The ball of the femur, trochanters, and proximal shaft to the level of the bottom of ischial tuberosities Gay HA, Barthold HJ, O′Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al. Pelvic normal tissue contouring guidelines for radiation therapy: A Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys 2012;83:e353-62.
  62. Problems with contouring for gynaec cancer on CT images • The GTV itself may/ may not be well seen • The parametrial disease is usually not visualized • Though pelvic nodal contouring is systematic, but we still tend to end up replicating the traditional cranio-caudal boundaries of a 4-field box • MR based guidelines are difficult to implement on CT • It is expensive to do routine MR-based planning • Problems with the availability of MR-based TPS
  63. IMRT in Ca Cervix • required inverse planning. • modulates the intensity of the beam using the motion of multileaf collimators. • Computerized software used to conform the dose to the shape of the target in 3D
  64. Rationale • Improved delivery of conventional doses • ↓Dose to normal tissues: small bowel, bladder, rectum, marrow • Dose escalation in high risk patients: node positive/gross residual disease • Replacement or integration with Brachytherapy
  65. Potentials of IMRT: as suggested by Dosimetric and small phase 2 studies For Whole Pelvic Treatments:  Reduction in acute small bowel morbidity.  Roeske JC, Bonta D, Mell LK, et al. A dosimetric analysis of acute gastrointestinal toxicity in women receiving intensity modulated whole- pelvic radiation therapy. Radiother Oncol 2003;69:201-207  Prevention of late term anorectal/ GI and GU dysfunction.  Mundt AJ, Mell LK, Roeske JC, et al. Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensitymodulated whole pelvic radiation therapyIJROBP 2003;56:1354-1360.  Reduction in acute hematological toxicity with bone marrow sparing.  Lujan AE, Mundt AJ, Yamada SD, et al. Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. IJROBP 2003;57:516-521.  For simultaneous extended field irradiation (± CCT).  Salama JK, Mundt AJ, Roeske J, Mehta N. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies. International Journal of Radiation Oncology*Biology*Physics. 2006 Jul 15;65(4):1170-1176.
  66. • Dosimetric studies have shown that IMRT can reduce bowel, rectal, bladder, and bone marrow dose, and early clinical studies have demonstrated lower rates of GI, genitourinary (GU), an hematologic toxicity compared with conventional techniques • the results of these studies should be taken with some caution because of • mainly single institution experiences • heterogeneity of the populations studied, • small numbers of patients • short follow up • great variability in margins, treatment fields and dose prescription Prospective studies comparing IMRT with conventional techniques are few
  67. • Reduction of dose to normal structures - ‘conformal avoidance’  (Lujan AE, Mundt AJ, Yamada SD, et al. Intensity- modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. IJROBP 2003;57:516-521.) Reduction in acute hematological toxicity with bone marrow sparing
  68. • Deliver multiple dose levels at one time • simultaneous in-field boost Mutic et al IJROBP 55 (2003) 28  For simultaneous extended field
  69. As an alternative to brachytherapy:  In distorted anatomy to circumvent limitations of brachytherapy.  To give higher dose to pelvic nodes present  In postoperative patients with residual central disease instead of interstitial brachytherapy. Suggested Potentials of IMRT
  70. Can IMRT replace brachytherapy? NO • Complex internal organ motion – Brachy fixed to target After 45 Gy EBRT
  71. Brachytherapy 12 (2013) 311e316 aimed to compare the dosimetry achieved by IBT and IMRT in patients not suitable for ICRT Results of study have shown that IBT provides superior dosimetry as compared with IMRT; and, therefore, IBT, as of now, remains the standard treatment for patients with cervical carcinoma who are not suitable for ICRT MATERIALS: The CT imaging data, previously used for IBT planning of 12 patients with cervical carcinoma, were transferred to IMRT planning system to generate parallel IMRT plans. Prescribed dose to the planning target volume (PTV) was 20 Gy delivered in 2-weekly high-dose-rate fractions of 10 Gy each with IBT (biologically equivalent dose [BED10] 40 Gy) and 33 Gy/13 fractions/2.5 wk with IMRT (BED10 41 Gy. RESULTS: For PTV, the meanD95 (dose received by 95% of PTV) was better with IBT (57.16 Gy vs. 41.47 Gy, p50.003). The mean conformity index was 0.94 and 0.90 with IBT and IMRT, respectively ( p50.034). IBT delivered significantly reduced doses to bladder and rectal volume as compared with IMRT.
  72. Imrt in post op setting: need for small bowel dose reduction  Conventional 4 field technique exposes most of the contents of the true pelvis to the prescribed dose (usually 45-50 Gy in 25-28 fractions).  This is of concern in post-op pts. since after hysterectomy, small bowel tends to fall into the vacated space in the true pelvis, increasing the amount of bowel treated to high dose.  It increases the risk of acute and late small bowel complications  The major potential advantage of IMRT in the postoperative setting, is the ability to shape a dose distribution that delivers a lower dose to intraperitoneal pelvic contents (i.e., small and large bowel) than to the surrounding pelvic lymph nodes.  This should make it possible to reduce the acute and late side effects of treatment
  73. • IMRT reduces small bowel dose by 50–67% as compared with conventional WPRT • Prospective studies evaluating IMRT have demonstrated 30% reduction in acute grade II toxicity and upto 30% reduction in the prescription of antidiarrhoeals  Portelance L, et al. Post-operative pelvic IMRT with chemotherapy for patients with cervical carcinoma/RTOG 0418 phase II study. IJROBP 2009;75:S640–1.  Schwarz JK, Wahab S, Grigsby PW. Prospective phase I/II trial of helical tomotherapy with or without chemotherapy for postoperative cervical cancer patients IJROBP2009;81:1258–63.  Kabarriti R, Thawani N, Gao W, et al. Feasibility and acute toxicity of intensity modulated radiation therapy with CDDP chemotherapy for postoperative pelvic radiation in patients with cervical cancer. IJROBP 2009;75:S376–7.  Vandecasteele K, Tummers P, Makar A, et al. Postoperative intensity modulated arc therapy for cervical and endometrial cancers: a prospective report on toxicity. IJROBP 2012;84:408–14.  Mundt AJ, Roeske JC. Can intensity-modulated radiation therapy replace brachytherapy in the management of cervical cancer? Counterpoint. Brachytherapy 2002;1:192–4. phase II studies have reported favourable outcomes with the use of IMRT Results of RTOG 0418 and study from TMH Mumbai awaited
  74. IMRT in intact cervix: problems • adequate margins in the intact cervix setting is debatable given significant organ motion during treatment. • Uncertainties in the definition of target volumes arise using 3D techniques. • Bladder-filling and rectal-filling changes require accurate definition of margins for the PTV. • With IMRT, there is a need for continual replanning (at least every other week), given rapid tumor regression and internal-organ motion.
  75. • To evaluate the toxicity and clinical outcome in patients with LACC treated with WP-CRT versus WP- IMRT • METHODS AND MATERIALS: • Between January 2010 and January 2012, • 44 patients with (FIGO 2009) stage IIB-IIIB SCC cervix randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m2 followed by high-dose-rate HDR) IICRT, 7 Gy to point A in 3 once-weekly sessions • In patients deemed unsuitable for ICRT, interstitial brachytherapy (IBT) 10 Gy in 2 once-weekly sessions based on our previous experience • Acute toxicity : graded according to the CTCAE version 3.0 • Late toxicity: graded according to RTOG • Primary end point :acute gastrointestinal toxicity • secondary endpoints: disease-free survival
  76. The median time to completion of treatment in the WP-CRT arm was 9.1 weeks(range, 8.3-12.9 weeks), and in the WP-IMRT arm it was 9.1 weeks (range, 8.3-11.7 weeks). The median number of chemotherapy cycles in both arms was 5 (range, 3-6). The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), in the WP-IMRT arm was 21.6 months (range, 7.7-34.4 months).
  77. RESULTS Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT
  78. RESULTS: At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP- IMRT group (P=.651) overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). CONCLUSION: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. LIMITATION: small sample sizes and short follow-up use of image guidance
  79. Caveats of IMRT  Significantly increased expenditure:  Machine with treatment capability  Imaging equipment: Planning and Verification  Software and Computer hardware  Extensive physics manpower and time required.  Immobilization: Patient setup must be accurate and reproducible  Contouring: Need accurate contouring to avoid misses.  Knowledge of Internal Motion: Margins could vary greatly depending on organ motion  Concerns with integral dose and secondary malignancy
  80. RADIATION SIDE EFFECTS •Acute Side Effects: Acute gastrointestinal side effects: include diarrhea, abdominal cramping, rectal discomfort, and occasionally, rectal bleeding, which may be caused by transient enteroproctitis. • Genitourinary symptoms:secondary to cystourethritis, are dysuria, frequency, and nocturia,microscopic or even gross hematuria.. • Skin reactions: erythema and dry or moist desquamation may develop in the perineum or intergluteal fold. • acute radiation vaginitis, superficial ulceration of the vagina, and vagianl stenosis can also occur
  81. •Late Side Effects: Late radiation effects are closely related to total doses given to the pelvic organs. • Retrovaginal or vesicovaginal fistula and proctitis or cystitis can occur but in small percentages. • Injury to the gastrointestinal tract usually appears within 2 years of radiation therapy • Complications of the urinary tract more frequently are seen 3- 4 years after treatment. • Vaginal stenosis is associated with dyspareunia • Anal incontinence is observed occasionally
  82. Thank you

Notas do Editor

  1. important aspects of radiation therapy for precise dose delivery
  2. . A technique using four isocentric fields weighted 2:1 anteroposterior–posteroanterior over lateral portals and 1.8-Gy fractions was described by Russell et al.348 to deliver high-dose therapy (56 to 61 Gy). Kodaira et al.349 evaluated a four-field para-aortic irradiation technique with 10-MV photons (mean, 50.4 Gy) in 97 patients with cervical cancer. The 5-year cause-specific survival rate was 32.2%. Grade 1 or 2 stomach and duodenum sequelae developed in 26.8%, grade 2 sequelae of small bowel in 3.1%, and grade 2 sequelae of bone in 3.1%. Rates of toxicity with IMRT may be lower.275
  3. Several institutions reported placing a midline block after a full course of external-beam treatment to the pelvis in order to boost for patients with persistent disease after approximately 45 to 50 Gy. When parametrial tumor persists, 50 to 60 Gy may be delivered to the parametria, with reduced anteroposterior–posteroanterior portals (8 by 12 cm for unilateral and 12 by 12 cm for bilateral parametrial coverage). However, careful estimation of dose to the small bowel, sigmoid, and rectum is needed. In the modern era, the use of highly conformal boosts with 3D planning allows an increase in normal-tissue sparing. Contours on CT of the parametrial and nodal region allow more precise tailoring of dose. For patients with enlarged nodes, when available, IMRT techniques may be best at providing conformal dose escalation to 54 to 65 Gy. Similarly, with and computerized optimization as available with high HDR or pulse–dose-rate (PDR) brachytherapy, the physician may cover the adjacent parametria using large enough fraction sizes that an additional external-beam boost is not needed. When one prescribes HDR brachytherapy, the per-fraction nodal dose is approximately 25% of prescription. In one study the per-fraction dose to the pelvic lymph nodes by HDR brachytherapy, when the high-risk clinical target volume (HR-CTV) received 5.5 Gy per fraction, was 1.4 Gy per fraction. Therefore, HDR brachytherapy may obviate the need for a parametrial boost, given the high per-fraction dose to the parametria and pelvic sidewall.344 In a comparison of three different approaches, Fenkell et al.345 reported on parametrial boost with midline shielding in six patients with locally advanced cervical cancer (IIB to IIIB) treated with definitive chemoradiotherapy and MRI-guided brachytherapy. A three-phase plan was modeled: 45-Gy (1.8 Gy per fraction) four-field box, 9-Gy (1.8 Gy per fraction) midline-shielded anteroposterior/posteroanterior fields (MBB), and intracavitary MRI-guided brachytherapy boost of 28 Gy (7 Gy per fraction). Midline shields 3, 4, and 5 cm wide were simulated for each patient. Brachytherapy and MBB plans were volumetrically summed. After a 4-cm MBB, HR-CTV D90 remained <85 Gy in all cases (mean, 74 Gy; range, 64 to 82 Gy). Bladder, rectum, or sigmoid D2ccincreased by > 50% of the boost dose in four of six patients. The authors concluded that a midline block may not be beneficial in patients receiving 3D image-planned brachytherapy with adequate optimization of dose to the tumor and away from the normal tissues.
  4. Treatments should be set up isocentrically
  5. Beam Energies For IMRT, 6-MV energy is used to provide the most homogeneous dose. However, in conventional irradiation, because of the thickness of the pelvis, high-energy photon beams (10 MV or higher) are especially suited for this treatment. They decrease the dose of radiation delivered to the peripheral normal tissues (particularly bladder and rectum) and provide a more homogeneous dose distribution in the central pelvis. With lower-energy photons (60Co or 4- to 6-MV x-rays), higher maximum doses must be given, and more complicated field arrangements should be used to achieve the same midplane tumor dose (three-field or four-field pelvic box or rotational techniques) while minimizing the dose to the bladder and rectum and to avoid subcutaneous fibrosis (Fig. 69.17).350 Biggs and Russell351 noted that the presence of a metallic prosthesis when using lateral fields or a box pelvic irradiation technique may result in a dose decrease of approximately 2% for 25-MV x-rays and average increases of 2% for 10-MV x-rays and 5% for 60Co. Allt352 and Johns,353 in an update of a randomized study, reported better pelvic tumor control and survival and fewer complications in 65 patients with stages IIB and III cervical carcinoma treated with 23-MV photons compared with 61 treated with external irradiation with 60Co in addition to brachytherapy in both groups. In contrast, Holcomb et al.350 compared outcome of 195 patients with stages IIB and IVA cervical carcinoma treated with 60Co radiation therapy (group 1) and 53 treated with linear accelerators (group 2). There was no significant difference in overall survival, although there was a trend toward increasing pelvic recurrence in the 60Co group (50.8%) compared with group 2 (35.8%; p = .08). Mixed-beam external radiation with neutrons and photons resulted in unacceptably high toxicity rates and is not recommended.354 Similarly, carbon-ion therapy was reported but resulted in major intestinal complication
  6. The exact locatio.
  7. The contour is extended around common iliac vessels posteriorly and laterally so as to include connective tissue between iliopsoas muscles and lateral surface of vertebral Body No additional 10mm anterolateral extension is given Around external iliac vessels along the iliopsoas muscle The posterior margin of CTV 1 contour over internal iliac vessels lies along anterior edge of piriformis muscle 7. Pre-sacral region is covered by connecting the volumes on each side of pelvis with a 10-mm strip over the anterior sacrum starting from aortic bifurcation till S2-S3 junction. Sacral foramina are not included in CTV 1 All visible nodes (contoured as GTV node) are given a margin of 10mm to create CTV node and are included in CTV 1 9. Muscle and bone are excluded from CTV 1.
  8. 78