Imrt In Gynecologic Malignancies

75 %
25 %
Information about Imrt In Gynecologic Malignancies
Health & Medicine

Published on February 27, 2009

Author: fovak

Source: slideshare.net

IMRT in Gynecologic Malignancies Arno J. Mundt MD Professor and Chair Department of Radiation Oncology University of California San Diego La Jolla CA

Background Intensity Modulated Radiation Therapy (IMRT) Computerized software used to conform the dose to the shape of the target in 3D, thereby reducing the volume of normal tissues receiving high doses Better sparing of normal tissues should mean less acute and chronic toxicity

Inverse process Target and normal tissues delineated on a planning CT Software used to deliver the dose to the target while minimizing dose to the normal tissues Accomplished by dividing beams into small “beamlets” Intensity of each beamlet individually optimized Red = high intensity Green = moderate intensity Yellow = low intensity

IMRT 4 Field When cast into the patient Highly conformal dose distributions are achieved

IMRT First conceived in the early 1960s Clinical implementation had to await development of computerized software 1st patient treated in 1992 (prostate)* Nearly all centers in the USA now have IMRT capability Increasingly available in Europe and Asia *first gynecology patient treated in early 1997

IMRT Becoming standard in many tumor sites (prostate and head/neck cancers) Strong evidence including randomized clinical trials have demonstrated its benefits Significant reductions in acute and chronic toxicities (dermatitis, xerostomia, proctitis) Better tumor control rates Prostate IMRT outcomes equivalent to radical prostatectomy

What about Gynecology? Growing in popularity 2002 IMRT Survey- 15% respondents using IMRT in gynecology patients 2004 IMRT Survey- 35% using IMRT in gynecology patients 4th most common site treated Most rapidly growing IMRT site Mell LK, Roeske JC, Mundt AJ. Survey of IMRT Use in the United States. Cancer 2003;98:204-211 Mell LK, Mundt AJ. Survey of IMRT Use in the USA- 2004 Cancer 2005;104:1296

100% Cancer 2005;104:1296 90% 80% Percent of Physicians 70% 60% 50% 40% 30% 20% 10% 0% 1992 1995 1998 2001 2004* *As of 8/04 Year

IMRT Practice Survey (2004) Site % __ Prostate 85% Head and Neck 80% CNS Tumors 64% Gynecology 35% Breast 28% GI 26% Sarcoma 20% Lung 22% Pediatrics 16% Lymphoma 12% Mell LK, Mundt AJ. Survey of IMRT Use in the USA- 2004 Cancer 2005;104:1296

Disease Sites Treated Resident Survey Site % Head and Neck 92% Prostate 81% CNS Tumors 56% Pediatrics 38% Gynecology 24% Recurrent/Palliative 24% Breast 21% GI 21% Lung 15% Lymphoma 7% Malik R, Mundt AJ et al. Tech Cancer Res Treat 2005;4:303

Gynecologic IMRT 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 Alternative/Replacement for Brachytherapy Heresy! Or is it?

Dosimetric (Planning) 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

To evaluate IMRT as a replacement for conventional whole pelvic RT (WPRT) Our goals were: To provide homogeneous dose coverage of the target tissues (PTV) ↓volume of small bowel, rectum and bladder irradiated Roeske JC, Mundt AJ et al. Int J Radiat Oncol Biol Phys 48:1613-1621, 2000

Chicago Study 10 pts (5 cervical, 5 uterine) Contrast-enhanced planning CT scan (oral, IV, rectal contrast) Clinical target volume (CTV) = upper 1/2 of the vagina, uterus (if present), parametria, and regional lymph nodes (common/external/internal iliacs, presacral nodes) Roeske et al. Int J Radiat Oncol Biol Phys 48:1613-1621, 2000

Intensity Modulated Pelvic RT Planning Studies ↓Volume Receiving Prescription Dose Author Bowel Bladder Rectum ↓50% ↓23% ↓23% Roeske ↓40-63%* Ahamad NS NS ↓70% ↓** ↓** Chen ↓51%*** ↓31%*** ↓66%*** Selvaraj *dependent on PTV expansion used **data not shown ***reduction in percent volume receiving 30 Gy or higher 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

Dosimetric IMRT Studies Benefits also seen in patients treated with more comprehensive fields Extended Field RT Portelance et al. Int J Radiat Oncol Biol Phys 2001;51:261 Chen et al. Int J Radiat Oncol Biol Phys 2001;51:232 Pelvic Inguinal RT Beriwal et al. Int J Radiat Oncol Biol Phys 2006;64:1395 Garofalo et al. RSNA 2002 Whole Abdominal RT Hong et al. Int J Radiat Oncol Biol Phys 2002;54:278 Duthoy et al. Int J Radiat Oncol Biol Phys 2003;57:1019

Extended Fields (Pelvic+Paraortic) •10 advanced cervical cancer patients •IMRT compared with 2 and 4 field techniques •Comparable target coverage •Significant ↓volume of normal tissues irradiated ↓Volume Receiving Prescription Dose Bowel Bladder Rectum ↓61% ↓96% ↓71% Versus 2 fields ↓60% ↓93% ↓56% Versus 4 fields Portelance et al. Int J Radiat Oncol Biol Phys 2001;51:261

Pelvic-Inguinal Fields • 9 vulvar pts • IMRT vs APPA plus electron fields • Volume of small bowel, rectum and bladder receiving ≥ 30 Gy reduced by 27%, 41% and 26% • No benefit for the femoral heads Beriwal et al. Int J Radiat Oncol Biol Phys 2006;64:1395

Extended Fields (Whole Abdomen) MSKCC • 10 endometrial cancer pts • IMRT vs conventional WART (with kidney blocks) • IMRT →↓dose to the bones and ↑target coverage with comparable kidney dose • Volume of pelvic bones irradiated ↓60% • Improved coverage of peritoneal cavity Hong et al. Int J Radiat Oncol Biol Phys 2002;54:278-289

Gynecologic IMRT Bone Marrow Sparing Approach Focus on small bowel and rectum Additional important organ is bone marrow 40% total BM is in the pelvis (within the RT fields) ↓Pelvic BM dose may ↑tolerance of concurrent chemotherapy and the chemotherapy at relapse

BM Sparing IM-WPRT To evaluate the ability of IMRT to ↓volume of BM irradiated, conventional and IMRT plans compared in terms of the volume of BM irradiated Focused on the iliac crests Lujan AE, Roeske JC, Mundt AJ. Int J Radiat Oncol Biol Phys 2003;57:516-521

100 90 80 70 Volume (%) 60 50 40 BMSparing-IM-WPRT 30 4 Field Box 20 10 0 0 10 20 30 40 50 Dose (Gy)

DVH Data Dose (Gy) 4-field Box BM-sparing IM-WPRT p-value (% BM volume) (% BM volume) 10 95.13 99.01 < 0.003 15 94.6 91.9 0.101 20 89.3 78.8 < 0.001 30 56.2 37.6 < 0.001 40 43.7 17.0 < 0.001 45 33.6 6.8 < 0.001 Lujan et al. Int J Radiat Oncol Biol Phys 2003;57:516

100% 95% 90% 70% 50% Isodose lines bend away from BM (crests)

Dosimetric (Planning) Studies Numerous investigators have also demonstrated that IMRT may allow safe dose escalation in high risk patients Exciting application is the use of IMRT to treat PET+ node using dose painting

Dose Escalation IMRT A simultaneous integrated boost (SIB) to high risk sites , e.g. +nodes (45 Gy/1.8 pelvis + 56 Gy/2.24 Gy involved site) Lujan AE, Mundt AJ, Roeske JC. Med Phys 2001;28:1262

Mutic et al. (Wash U) Int J Radiat Oncol Biol Phys 2003;55:28-35 • SIB technique to irradiate PA+ cervical cancer patients • PA region receives 50.4/1.53 daily fractions and the involved PA nodes receives 59.4 Gy/1.8 Gy daily fractions

Alternative/Replacement for Brachytherapy Very contentious issue Highly conformal plans are possible Unclear whether biologically equivalent

Roeske, Mundt et al. Med Physics 2000;27:1382 On average, total dose = 79 Gy (45 Gy pelvic RT + 34 Gy boost) possible With smaller margins, higher doses possible 0.25 cm margin → 84 Gy or higher

Brachytherapy vs IMRT Low et al. (Washington U) Int J Radiat Oncol Biol Phys 52:1400, 2002 Applicator guided IMRT in place of brachytherapy Applicator provides immobilization and spatial registration of the cervix, uterus and normal tissues Treat using HDR schedules Top=IMRT, bottom=HDR brachy

Others have proposed using a simultaneous integrated boost (SIB) Guerrero et al. Int J Radiat Oncol Biol Phys 2005;62:933 SIB approach 45 Gy in 1.8 Gy fractions (pelvis) 70 Gy in 2.8 Gy fractions (cervical tumor) Radiobiologically ≈ 45 Gy + 30 Gy HDR (5 fx) Better bowel and bladder sparing Shortens overall treatment to 5 weeks

Clinical Studies

Clinical Studies Increasing number of clinical studies suggest a benefit to IMRT Reductions in acute and chronic toxicity Same or better tumor control However, follow-up remains short and patient numbers are limited

40 pts 100 Cervical and Uterine Pts 90 IM-pelvic RT +/- Brachy 80 40 matched conventional pts 70 60 IM-WPRT 50 WPRT 40 30 20 10 0 Grade 0 Grade 1 Grade 2 Grade 3

NTCP Analysis Acute GI Toxicity 1 1 NTCP = 0.9 3 .2 ⎛ 410 ⎞ 0.8 1+ ⎜ ⎟ ⎜V ⎟ ⎝ 100 ⎠ 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0 100 200 300 400 500 600 Volume (cc) Roeske JC, Mundt AJ et al. Radiother Oncol 2003;56:1354)

Acute Toxicity Pelvic/Inguinal IMRT Beriwal et al. Int J Radiat Oncol Biol Phys 2006;64:1395 15 vulvar pts 7 preop (46 Gy), 8 postop (50.4 Gy) Well tolerated (only 1 acute grade 3 toxicity) Grade 1 2 3 4 GI 60% 20% 6% 0% GU 6% 13% 0% 0% Skin 26% 73% 0% 0%

Acute Toxicity Pelvic/Paraortic (Extended field) IMRT Gerszten et al. Gynecol Oncol 2006;102:182 22 cervical cancer pts 45 Gy/1.8 Gy fractions + 55 Gy/2.2 Gy fractions to +PET nodes All received concomitant cisplatin Low rates of acute toxicity Grade 1 2 3 4 GI 38% 10% 0% 0% GU 24% 10% 0% 0% Skin 5% 10% 0% 0%

Acute Toxicity Pelvic/Paraortic (Extended field) IMRT Salama J, Mundt AJ et al. Int J Radiat Oncol Biol Phys 2006;65:1170 13 pts (8 endometrial, 5 cervical) 45 Gy/1.8 Gy fractions 12 chemo (5 pre-RT, 5 concomitant, 5 post-RT No grade 3 GU or GI acute toxicities Grade 1 2 3 4 GI Diarrhea 15% 84% 0% 0% Nausea 38% 54% 0% 0% GU Dysuria 15% 7% 0% 0%

Acute Toxicity GI GU n g2 g3 g2 g3 Pelvis Mundt 40 60% 0% 10% 0% Chen 33 24% 0% 12% 0% Beriwal 47 70% 0% 4% 0% Pelvic-Paraortic Salama 13 84% 0% 7% 0% Beriwal 36 69% 3% 19% 3% Gerszten 22 10% 0% 10% 0% Pelvic-Inguinal Beriwal 15 20% 6% 13% 0% Mundt et al. Red J 2002;52 1330 Beriwal et al. Red J 2006;64:1395 Chen et al. Red J 2007;67:1438 Beriwal et al. Red J 2007;68:166 Beriwal et al. Gyne Oncol 2006;102:1395 Gerszten Gyne Oncol 2006;102:182 Salama et al. Red J 2006;65:1170

Hematologic Toxicity Acute hematologic toxicity also reduced with IMRT A surprise finding comparing Conventional and IMRT pts BM not intentionally spared. But it received less dose due to highly conformal plans Brixey C, Roeske JC, Mundt AJ. Int J Radiat Oncol Biol Phys 54:1388-93, 2002.

Grade ≥ 2 WBC Toxicity WPRT versus IM-WPRT Patients 60% 50% 40% WPRT 30% IM-WPRT 20% 10% 0% RT Alone RT + Chemo p = 0.08 p = 0.82 Brixey et al. Int J Radiat Oncol Biol Phys 52:1388-93, 2002

IM-WPRT resulted in a lower rate of decline of WBC counts during therapy Brixey C, Roeske J, Mundt A Int J Radiat Oncol Biol Phys 52:1388-93, 2002

BM-Sparing IMRT Led us to develop BM-sparing plans by intentionally sparing the iliac crests However, the iliac crests may not be the structures to avoid

Predictors of Hematologic Toxicity 37 cervical cancer pts treated with IMRT plus Cisplatin (40 mg/m2/week) Predictors of hematologic toxicity and chemotherapy delivery: Total Pelvic Bone Marrow V10 and V20 Lumbosacral Spine Bone Marrow V10 and V20 Volume of the iliac crests irradiated not correlated with hematologic toxicity Mell LK, Roeske JC, Mundt AJ Int J Radiat Oncol Biol Phys 2006;66:1356

Grade ≥ 2 Grade ≥ 2 Chemo n WBC ANC Held Pelvic BM V-10 ≤90% 18 11% 74% 16% >90% 19 74% 32% 48% p < 0.01 p = 0.09 p = 0.08 Pelvic BM V-20 ≤75% 21 24% 14% 24% >75% 16 68% 25% 44% p < 0.01 p = 044 p = 0.20

90% 80% 70% 60% 50% IM-WPRT 40% WPRT 30% 20% 10% 0% 0 1 2 3 On multivariate analysis controlling for age, chemo, stage and site, IMRT remained statistically significant ( p = 0.01; OR = 0.16, 95% confidence interval 0.04, 0.67)

Chronic Toxicity Beriwal et al. Gynecol Oncol 2006;102:195 47 endometrial cancer pts Postop IMRT (39 pelvis, 8 pelvic+paraortic) Median follow-up = 20 months SBO Grade 1 2 3 4 GI 28% 0% 2% 0% GU 14% 0% 0% 0% 3-year actuarial grade ≥2 toxicity = 3.3%

Chronic Toxicity GI GU n g2 g3 g2 g3 Pelvis Mundt 35 2.8% 0% 0% 0% Chen 33 0% 0% 0% 3% Beriwal 47 0% 0% 0% 0% Pelvic-Paraortic Beriwal 36 2.7% 5.5% 0% 0% Mundt et al. Red J 2003;56:1354 Chen et al. Red J 2007;67:1438 Beriwal et al. Gyne Oncol 2006;102:1395 Beriwal et al. Red J 2006;64:1395

Tumor Control Very little data Single institution experiences Short followup But promising

Cervical Cancer Pelvic n FU Stage DFS Control Intact Cervix Kochanski 44 23 m I-IIA 81% 93% IIB-IIIB 53% 67% Beriwal 36 18 m IB-IVA 51% 80% Postoperative Cervix Kochanski 18 21 m I-II (node+) 79% 94% Chen 35 35 m I-II (node+) NS 93% 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

Endometrial Cancer Pelvic n FU Stage DFS Control Knab 31 24 m I-III 84% 100% Beriwal 47 20 m I-III 84% 100% Knab et al. Int J Radiat Oncol Biol Phys 2004;60:303 Beriwal et al. Int J Radiat Oncol Biol Phys 2006;102:195

Current Research Directions Guidelines/Consensus Multi-institutional Trials Image-Guidance

Clinical Trials Important to move from single institution to multi-institutional, prospective clinical trials Ideally, multi-national studies given incidence of cervical cancer outside of USA

RTOG 0418 Preliminary Results ASTRO 2008 58 patients enrolled (25 centers) 28% Grade ≥ 2 acute toxicity, primarily Gastrointestinal Majority of CTVs drawn per protocol

Tata Memorial Hospital Mumbai India Phase II randomized trial (ongoing) Conventional RT vs IMRT To date, 58 Cervical Cancer pts Grade 2 or higher GI, GU, neutropenia Conventional: 28%, 10% and 10% IMRT: 14%, 3%, and 3% 14 month median followup: No difference in response or tumor control

Guidelines/Consensus Little consensus exists on how gynecologic IMRT should be planned and delivered Hampers widespread implementation Hampers development of multi- institutional clinical trials

Controversial Issues Optimal positioning (prone vs supine) CTV components (?whole uterus in early stage patients) CTV delineation Optimal CTV-PTV margin Organ motion issues Which normal tissues should be avoided? Optimal beam configuration. Optimal beam energy. Et cetera, et cetera…..

Example: Positioning University of Chicago UCSD MD Anderson University of Colorado

RTOG-GOG-ESTRO-NCIC Consensus Conference Consensus conference on target design June 2005 CTV in the postoperative cervix or uterine patient Guideline for the current RTOG trial Atlas on RTOG website Published in the Red Journal

Most exciting area of research: image-guided IMRT

Advances in Gynecologic RT Standard IMRT W RT A L L Benefits

Key to Further Advancements IMRT IG-IMRT

Thank You

Add a comment

Related presentations

Related pages

IMRT for Gynecologic Malignancies: The University of ...

IMRT for Gynecologic Malignancies: The University of Chicago Experience Bulent Aydogan, PhD John C. Roeske, PhD The University of Chicago
Read more

IMRT and IGRT in Gynecologic Malignancies

IMRT and IGRT in Gynecologic Malignancies Arno J. Mundt, M.D. Professor and Chairman Department of Radiation Oncology University of California San Diego
Read more

Role of IMRT in the Treatment of Gynecologic Malignancies

Role of IMRT in the Treatment of Gynecologic Malignancies John C. Roeske, PhD Associate Professor The University of Chicago
Read more

Intensity Modulated and Image Guided Radiation Therapy in ...

Intensity Modulated and Image Guided Radiation Therapy in Gynecologic Malignancies Arno J. Mundt, M.D. Professor and Chairman Department of Radiation Oncology
Read more

Intensity-Modulated Radiation Therapy in Gynecologic ...

Clinical Advances in Hematology & Oncology Volume 4, Issue 5 May 2006 379 Intensity-Modulated Radiation Therapy in Gynecologic Malignancies: Current Status
Read more

Intensity-modulated radiation therapy in gynecologic ...

Radiation therapy (RT) is commonly used in the treatment of gynecologic malignancies. Unfortunately, RT exposes patients to a wide variety of sequelae.
Read more

Imrt In Gynecologic Malignancies - Health & Medicine

1. IMRT in Gynecologic Malignancies Arno J. Mundt MD Professor and Chair Department of ...
Read more

Intensity-modulated radiation therapy in gynecologic ...

Intensity-modulated radiation therapy in gynecologic malignancies. ... Unlike conventional approaches, IMRT conforms the prescription dose to the shape ...
Read more