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IMRT IN CANCER CERVIX ? Aug 2010 Dr. T. SUJIT AMO , Radiation Oncology Valavadi Narayanaswamy Cancer Centre GKNM Hospital , Coimbatore, INDIA
Cleaves M. Radium: With a preliminary note on radium rays in the treatment of cancer. Med Rec 1903;64:601–606. INTRODUCTION RT has a long history in the treatment of gynecologic malignancies, notably cervical cancer. We have come a long way since the 1st gynecology patient was treated with RT more than a century ago
Developments and technical progress in medical field parallels that in computational prowess. Major advancements in RT planning and delivery in recent years Particularly true of EBRT – from 3DCRT to Cyber-knife and Arc Therapy Gordon Isaacs, the first patient treated with the linear accelerator (radiation therapy) for retinoblastoma in 1957. Gordon's right eye was removed January 11, 1957 because the cancer had spread. His left eye, however, had only a localized tumor that prompted Henry Kaplan to try to treat it with the electron beam. Gordon is now living in the east bay, and his vision in the left eye is normal. TECHNOLOGICAL PROGRESS - Yes , . . .
Radiation treatment of Ca Cervix has lagged behind in adopting newer RT delivery techniques < 15% Oncologists use IMRT for Ca cervix even in the west ! Brachytherapy – still prescribed to a point instead of volume ! Mell LK, Mundt AJ Survey of IMRT Use in the United States Cancer . . . HOWEVER ,
EBRT : to treat whole pelvis BRACHYTHERAPY : to boost the dose to primary tumor EBRT : 50 – 60 Gy in 2 Gy fractions Brachytherapy ~ either LDR or HDR ICB ± interstitial implants ~ 3 to 5 fractions recommended Total combined dose to point A : 70 – 80 Gy Total treatment time : 5 – 6 weeks TRADITIONAL SCHEME OF RT
V N C C SCHEME
4 FIELD AP – PA ~ MIDLINE SHIELD / PM BOOST ~ INGUINAL FIELDS ~ PALN FIELD TRADITIONAL FIELD ARRANGEMENTS
POSITIONING – supine vs prone CTV DELINEATION - contrast CT - bio-radiological imaging - image fusion DOSE ESCALATION vs NORMAL TISSUE SPARING ANATOMICAL VARIATIONS - tumor regression - bladder and rectal filling CHALLENGES IN EBRT OF CA Cx
Conventional RT -> toxicities due to the inclusion of considerable volumes of various normal tissues
Small bowel -> diarrhea, SBO, enteritis, malabsorption
Reduction in the volume of normal tissues irradiated with IMRT may thus ↓risk of acute and chronic RT sequelae
Allow for simultaneous boost of involved lymph nodes
? Alternative to conventional brachytherapy
RATIONALE OF USING IMRT IN CA Cx
For Whole Pelvic Treatments:
Reduction in acute small bowel morbidity.
Reduction in acute hematological toxicity with bone marrow sparing.
Prevention of late term anorectal / GI and GU dysfunction.
Escalation of dose to the pelvic lymph nodes.
Better matching of dose profiles in simultaneous treatments.
For simultaneous extended field irradiation .
Better target coverage with modern day improvements in conjunction with image based brachytherapy
As an alternative to brachytherapy:
In distorted anatomy to circumvent limitations of brachytherapy.
To give higher dose to pelvic nodes present at time of BT.
In postoperative patients with residual central disease instead of interstitial brachytherapy .
RATIONALE OF USING IMRT IN CA Cx
PLAN OK PLAN NOT OK : RE-DO THE IMRT PROCESS SIMULATION TARGET DELINEATION NORMAL TISSUE CONSTRAINTS TREATMENT PLANNING AND OPTIMISATION PLAN EVALUATION QA - PHANTOM TREATMENT DELIVERY VERIFICATION
Int. J. Radiation Oncology Biol. Phys., - IN PRESS. Gynaec IMRT Consortium : RTOG; National Cancer Institute of Canada; Japan Clinical Oncology Group; and European Society of Therapeutic Radiology and Oncology (ESTRO). IMRT – CONSENSUS GUIDELINES FOR CTV
Numerous published clinical studies : Kochanski et al. Int J Radiat Oncol Biol Phys 2005;63:214 Beriwal et al. Int J Radiat Oncol Biol Phys 2007;68:166 Chen et al. Int J Radiat Oncol Biol Phys 2001;51:332 IMRT STUDIES IN CA Cx CLINICAL STUDIES
Tata Memorial Hospital
Phase II randomized trial
Conventional RT vs IMRT
58 Cervical Cancer pts ( as of Jan 2009 )
Grade 2 or higher GI, GU, neutropenia
~ Conventional: 28%, 10% and 10%
~ IMRT: 14%, 3%, and 3%
14 month median follow up:
~ No difference in response or tumor control
IMRT STUDIES IN CA Cx CLINICAL STUDIES – INDIAN DATA
IMRT STUDIES IN CA Cx IMRT Vs CONVENTIONAL RT – DOSIMETRIC STUDIES
Numerous investigators have compared IMRT and conventional RT
All have shown a benefit to IMRT
Comparable or better target coverage
Improved sparing of normal tissues
Author Bowel Bladder Rectum Roeske ↓ 50% ↓ 23% ↓ 23% Ahamad ↓ 40-63% ↓ NS ↓ NS Chen ↓ 70% ↓ N S ↓ NS Selvaraj ↓ 51% ↓ 31% ↓ 66% * NS – data not shown Roeske et al. Int J Radiat Oncol Biol Phys 2000;48:1613 Ahamad et al. Int J Radiat Oncol Biol Phys 2002;54:42 Heron et al. Gynecol Oncol 2003;91:39-45 Chen et al. Int J Radiat Oncol Biol Phys 2001;51:332 Whole Pelvic RT ( WPRT )
IMRT STUDIES IN CA Cx IMRT Vs CONVENTIONAL RT – DOSIMETRIC STUDIES Extended Fields (Pelvic + Para aortic)
IMRT compared with 2 and 4 field techniques
Comparable target coverage
Significant ↓ volume of normal tissues irradiated
Bowel Bladder Rectum Versus 2 fields ↓ 61% ↓ 96% ↓ 71% Versus 4 fields ↓ 60% ↓ 93% ↓ 56% % Reduction in Volume Receiving Prescription Dose Portelance et al. Int J Radiat Oncol Biol Phys 2001;51:261
IMRT STUDIES IN CA Cx IMRT Vs CONVENTIONAL RT – DOSIMETRIC STUDIES GI Toxicity Comparison - IMRT vs WPRT ACUTE GI TOXICITY CHRONIC GI TOXICITY Mundt et al. IntJ RadiatOncolBiolPhys 52:1330-1337, 2002
Traditional OAR in pelvic RT : small bowel, rectum , bladder
Bone marrow is an important OAR
40-50% of active bone marrow lies within RT fields (WPRT)
↓ bone marrow dose = ↓ haematologic toxicity
Major predictors of hematologic toxicity:
Total pelvic BM V-10 and V-20
Lumbar sacral spine
( Not volume of the iliac crests )
↓ pelvic BM dose may ↑ tolerance of concurrent chemotherapy
Brixeyet al. IntJ RadiatOncolBiolPhys 52:1388-93, 2002 Mell LK, KochanskiJ, RoeskeJC, et al.IntJ RadiatOncolBiolPhys (In press) IMRT – BONE MARROW SPARING
WPRT - 4FB IMRT Versus Grade ≥2 WBC Toxicity IMRT – BONE MARROW SPARING
IMRT allows safe dose escalation in high risk patients
“ Dose painting” in conjunction with PET-CT
Simultaneous Integrated Boost ( SIB ) to high risk sites
Ahmed et al. IMRT dose escalation for positive PA nodes in locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2004 ; 60 ; 505 IMRT – DOSE ESCALATION 60 Gy in 2.4 Gy / day 45 Gy in 1.8 Gy / day
Significantly increased expenditure:
Machine with treatment capability
Imaging equipment: Planning and Verification
Software and Computer hardware
Extensive physics manpower and time required.
Conformal nature – highly susceptible to motion and setup related errors – Achilles heel of CFRT
Target delineation remains problematic.
Decreased “dose-rate” to the tumor
Increased integral dose (Cyberknife > Tomotherapy > IMRT)
IMRT - DRAWBACKS
Possible reasons for lack of development of BT compared to EBRT : clinical results of BT have been better than EBRT, although its application is limited by the tumor size. Therefore, there has been less impetus for development. opportunity for dose optimisation is limited with traditional LDR techniques. traditional applicator designs cause artefacts in modern imaging techniques. CT / MRI compatible applicators : 3D image guided planning FDG-PET image fusion : better tumor delineation in relation to the brachy applicators Electronic Brachytherapy : currently approved in the US for APBI (Axxent™ Electronic Brachytherapy System ). ? Ca cx ADVANCES IN BRACHYTHERAPY
BENEFITS OF CROSS SECTIONAL IMAGING - ACCURATE VERIFICATION OF APPLICATOR POSITION - ACCURATE DEFINITION OF NORMAL TISSUE DOSIMETRY ~ DVH instead of conventional point doses - CONFORMAL DOSE DISTRIBUTIONS TO TUMOR & OAR ~ 3D optimisation improves tumor target dose coverage - OPPORTUNITY FOR DOSE ESCALATION ~ possibility of increasing the dose to 95% of the target volume by 124% using CT based planning and 138% using MRI based planning (compared to conventional planning) Potter R, Dimopoulos J, Georg P et al. Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol 2007; 83(2): 148 - 155. IMAGE GUIDED BRACHYHERAPY (IGBT)
Radiotherapy Oncology 2006:78:67-77 Radiotherapy and Oncology 74 (2005) 235–245 GUIDELINES FOR THE FIRST TIME IN BRACHYTHERAPY – RISK STRATIFICATION IMAGE GUIDED BRACHYHERAPY (IGBT)
Is there any evidence that IMRT could replace brachytherapy? ~ Multiple dosimetric studies suggest that an IMRT boost is feasible ~ Clinical outcome data, however, is extremely limited Max. rectal doses lower with IMRT vs. HDR (89% vs. 143%, p < 0.05) Mean rectal doses in IMRT lower than HDR (14.8% vs. 21.4%, p < 0.05) IMRT resulted in lower max. bladder doses (66.2% vs. 74.1%, p < 0.05) Plans provided comparable coverage to the PTV with IMRT plans resulting in less dose heterogeneity AydoganB. IntJ RadiatOncolBiolPhys 65:266-73, 2006. IMRT Vs BRACHYTHERAPY
IMRT Vs BRACHYTHERAPY I M R T BRACHYTHERAPY PTV RECTUM BLADDER RECTUM BLADDER PTV
Most IMRT vs BT studies have pitted hi-tech EBRT against conventional BT “ Georg D, Kirisits C,et al.Image-guided radiotherapy for cervix cancer: high-tech external beam therapy versus high-tech brachytherapy . Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1272-8. Epub 2008 May 19. ” IMRT / IMPT ( protons) vs image guided BT HI-TECH EBRT Vs HI-TECH BT
Any comparison between EBRT and BT is influenced by the choice of dose and dose volume constraints for relevant structures. For image-guided cervix cancer treatments, both IMRT and IMPT seem to be inferior to BT. Issues to be addressed : ~ whether image-guided adaptive BT can utilize the dose reduction in OAR that can be achieved with high-tech EBT, to further improve the therapeutic ratio and consequently outcome. ~ whether advanced adaptive EBRT can complement advanced adaptive BT in its shortcomings,which are mainly in lymph nodes and maybe for pelvic sidewall disease HI-TECH EBRT Vs HI-TECH BT
Can IMRT Replace Brachytherapy in Cervical Cancer? Given excellent efficacy and tolerance of modern brachytherapy, no need to replace it At best, IMRT could provide a potential fallback for patients unable or unwilling to receive brachytherapy BUT. . . are we asking the right question ? THE $ 1000,000 QUESTION . . .
Can IMRT and Brachytherapy be integrated ? POTENTIAL BENEFITS : ~ “Repair” unacceptable brachytherapy implants ~ Optimize parametrial boosts in locally advanced cervical cancer IMRT -> ADAPTIVE TECHNIQUES : IGRT + BT -> IMAGE GUIDED 3D BRACHYTHERAPY ADAPTIVE BRACHYTHERAPY THE WAY FORWARD . . . ADAPTIVE IG - IMRT ADDITIONAL IG-IMRT