ASTRO News Brie iefin ing: In Innovations in in RT Deliv livery - - PowerPoint PPT Presentation

ASTRO News Brie iefin ing: In Innovations in in RT Deliv livery ry

Tuesday, September 27, 1:30-2:30pm ET Moderator: Geraldine M. Jacobson, MD, MPH, MBA, FASTRO, West Virginia University

• A Pha

hase II III I Ra Randomiz ized Tria rial l Com

• mparin

ing Pati tient Rep eport rted Toxi xicit ity and and Qua uali lity ty of

• f Life (Q

(QOL) Duri uring Pelv elvic IM IMRT T as as Com

• mpared to
• Con
• nventio

ional l RT RT

Ann H. Klopp, MD, PhD, MD Anderson Cancer Center

• Ra

Radia iatio ion Boo

• ost for
• r Duc

uctal l Car arcin inoma In In Situ tu Aft fter r Who hole le Breast Ra Radiatio ion Th Ther erapy (W (WBRT) T) Im Impr proves Loc

• cal Con
• ntr

trol: Ana nalysis is fr from

• m Ten

en Poo

• ole

led Academic ic Ins Instit itutio ions

Meena S. Moran, MD, Yale University

• Res

esult lts of

• f COG ACNS0331: A Pha

hase II III Tria rial l of

• f In

Involv lved-Field ld Ra Radiotherapy (I (IFRT) T) and and Low Dose

• se

Cran aniospinal Irr Irradia iatio ion (LD (LD-CSI) with Che hemotherapy in n Aver erage-Ris isk Med edullo lobla lastoma: A Rep eport t from the Children’s Oncology Group

Jeff M. Michalski, MD, MBA, FASTRO, Washington University in St. Louis

https://www.astro.org/uploadedFiles/_MAIN_SITE/Meetings_a nd_Education/ASTRO_Meetings/2016/Annual_Meeting/Conten t_Pieces/AllDisclosures.pdf

A Phase III III Randomized Trial Comparing Pati tient Reported Toxicity and Quality of f Li Life (Q (QOL) During Pelvic IM IMRT as Compared to Conventional RT

• A. H. Klopp1, A. R. Yeung2, S. Deshmukh3, K. M. Gil4, L. Wenzel5, S. N. Westin1, K. Gifford1, D. K. Gaffney6, W.

Small Jr7, S. Thompson8, D. E. Doncals9, G. H. C. Cantuaria10, B. Yaremko11, A. Chang12, V. Kundapur13, D. S. Mohan14, M. L. Haas15, Y. B. Kim16, C. L. Ferguson17, and D. W. Bruner18

1MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, University of Florida, Gainesville, FL, 3American

College of Radiology, Philadelphia, PA, 4Summa Health System, Akron, OH, 5University of California, Irvine, Irvine, CA, 6Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 7Stritch School of Medicine, Loyola University Chicago, Maywood, IL,

8Stephenson Cancer Center, Oklahoma City, OK, 9SUMMA Akron City Hospital, Akron, OH, 10Northside Hospital, St. Petersburg, FL, 11London Regional Cancer Program, London, ON, Canada, 12Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong, 13Saskatoon Cancer Centre, Saskatoon, SK, Canada, 14Kaiser Permanente Cancer Treatment Center, San Francisco, CA, 15Reading

Hospital, Reading, PA, 16Yonsei University Health System-Severance Hospital, Sinchon-dong, Korea, The Republic of, 17Georgia Regents University, Augusta, GA, 18Nell Hodgson Woodruff School of Nursing, Winship Cancer Institute at Emory University, Atlanta, GA

IM IMRT for post-operative pelvic RT RT

• IMRT reduces the dose delivered to small bowel in center of pelvis.
• Retrospective studies show lower rates of acute and chronic GI

toxicity with IMRT as compared to standard 4-field RT.

• RTOG 0418 found IMRT to be feasible with a favorable rate of acute

2+ GI toxicity (25%).

Study Schema

Eligibility

Women with endometrial or cervical cancer requiring post-op pelvic RT or chemoRT

Stratification Factors Disease Site: Endometrial, Cervix XRT Dose: 45 Gy, 50.4 Gy Chemo: No chemo, 5 cycles of weekly cisplatin at 40mg/m2 RANDOMIZE IMRT pelvic radiation treatment 4-field pelvic radiation treatment

Treatment Planning

• Nodal CTV
• RTOG atlas
• Vaginal
• ITV w bladder full and empty
• 7mm PTV expansion
• OARs: Bone marrow, bowel,

bladder, rectum Rapid review of contours and plans required on the first case on each arm for a site.

• IMRT planning
• Standard RT

EPIC Bowel Questions

Bowel Function:

• rectal urgency?
• uncontrolled leakage of stool?
• stools that were loose?
• bloody stools?
• your bowel movements been painful?

How often have you had… How many bowel movements have you had on a typical day? How often have you had crampy pain in your abdomen or pelvis? Bowel Bother:

• has each of these issues been for you?
• have your bowel habits been for you?

How big

• f a problem…

EPIC Bowel Score

50 70 90

Baseline Week 3 of RT Week 5 of RT 4-6 weeks post-RT IMRT 128 113 111 102 4 Field 148 132 130 125 p-value = 0.048

IMRT 4-field

Pro-CTCAE Results

10 20 30 40 50 60

standard IMRT

Percent of patients with PRO- CTCAE Score ≥3 at 5 weeks

Abdominal pain Diarrhea Fecal incontinence

Frequency Interference Frequency Interference

* * *

*, p <0.05

Use of f Anti-Diarrheal Medications

0% 10% 20% 30% 40% 50% 60% 70% 0 or 1 2 or 3 4 or more standard IMRT

Percentage of patients

Number of anti-diarrheal medications daily

p <0.05

Quality of Life: FACT CT-Cx Cx

Physical well-being Energy, pain, feeling ill, time in bed, nausea, meeting needs of family Social well-being Emotional well-being Functional well-being Work, enjoy life, accept illness, sleep well Additional treatment related concerns Vaginal symptoms, interest in sex, body appearance, urinary fxn, appetite

Trial Outcome Index

Quality of Life: FACT CT-Cx Cx

Change in FACT-Cx

IMRT 4 Field p-value Physical Well-Being (n=86) (n=106) Mean

• 4.2
• 6.1

0.03

• Std. Dev.

6.0 6.1

Add’l treatment concerns (n=87) (n=104) Mean

• 2.7
• 4.9

0.01

• Std. Dev.

6.1 6.5

Trial Outcome Index (n=86) (n=106) Mean

• 8.8
• 12.8

0.06

• Std. Dev.

14.4 14.3

Conclusions

• Pelvic IMRT reduces acute patient reported GI and GU toxicity

compared to standard pelvic RT.

• Pelvic IMRT reduces need for anti-diarrheal medications as compared

to standard pelvic RT.

• Pelvic IMRT improves quality of life with regard to physical

functioning and other treatment effects during treatment .

• Longer term follow up will be needed to determine if these

differences in acute toxicity result in lower rates of late toxicity.

ASTRO News Brie iefin ing: In Innovations in in RT Deliv livery ry

Tuesday, September 27, 1:30-2:30pm ET Moderator: Geraldine M. Jacobson, MD, MPH, MBA, FASTRO, West Virginia University

• A Phase III Randomized Trial Comparing Patient Reported Toxicity and Quality of Life (QOL)

During Pelvic IMRT as Compared to Conventional RT

Ann H. Klopp, MD, PhD, MD Anderson Cancer Center

• Ra

Radia iatio ion Boo

• ost for
• r Duc

uctal l Car arcin inoma In In Situ tu Aft fter r Who hole le Breast Ra Radiatio ion Th Ther erapy (W (WBRT) T) Im Impr proves Loc

• cal Con
• ntr

trol: Ana nalysis is fr from

• m Ten

en Poo

• ole

led Academic ic Ins Instit itutio ions

Mee eena S.

• S. Moran, MD, Yale

le Unive iversity

• Results of COG ACNS0331: A Phase III Trial of Involved-Field Radiotherapy (IFRT) and Low Dose

Craniospinal Irradiation (LD-CSI) with Chemotherapy in Average-Risk Medulloblastoma: A Report from the Children’s Oncology Group

Jeff M. Michalski, MD, MBA, FASTRO, Washington University in St. Louis

Radiation Boost for Ductal Carcinoma In In Si Situ Aft fter Whole Breast Radiation Th Therapy (W (WBRT) ) Im Improves Lo Local Control: Analysis fr from Ten Pooled Academic In Institutions

• M. S. Moran1, Y. Zhao1, S. Ma1, Y. M. Kirova2, A. Fourquet3, P. Y. Chen4, K. E. Hoffman5, K. K. Hunt6, J. S.

Wong7, L. M. Halasz8, G. M. Freedman9, R. G. Prosnitz10, M. Yassa11, D. H. A. Nguyen11, T. Hijal12, B. G. Haffty13, E. S. Wai14, and P. Truong15

1Yale University, New Haven, CT, 2Institut Curie, Paris, France, 3Institut Curie, Paris 75005, France, 4Beaumont Health System, Royal

Oak, MI, 5The University of Texas MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, 6MD Anderson Cancer Center, Houston, TX, 7Brigham and Women's Hospital, Boston, MA, 8University of Washington, Department of Radiation Oncology, Seattle, WA, 9University of Pennsylvania, Department of Radiation Oncology, Philadelphia, PA, 10Allentown Radiation Oncology Associates, Allentown, PA, 11Maisonneuve-Rosemont Hospital, Montreal, QC, Canada, 12McGill University Health Centre, Montreal, QC, Canada, 13Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 14BC Cancer Agency, Surrey, BC, Canada, 15British Columbia Cancer Agency, Victoria, BC, Canada

Background

• Breast Conservation Therapy (BCT), defined as local excision to remove

the tumor followed by whole breast radiation therapy (WBRT), is a standard treatment option for early-stage breast cancers

• After WBRT, a common practice is delivery of a “radiation boost”

directed to the tumor bed whereby an additional 4-8 fractions allow for dose-escalation to the region at highest risk for local recurrence

• The practice of ‘boosting’ has been demonstrated to provide a small but

statistically significant reduction in IBTR risk in all age groups for invasive cancers (4% at 20 years) but robust data for DCIS specifically are lacking

Background

• Because DCIS has an excellent prognosis with very few recurrences after

WBRT, demonstrating similar results specific to DCIS require large numbers of patients with very long follow up

• The purpose of this study was to create a DCIS database of patients

treated with WBRT with and without a boost, to analyze the effects of the boost specifically for DCIS

Method

• An a priori power calculation was conducted to determine the number of patients

needed to demonstrate a significant difference of 3% between boost and no-boost

• >2,982 patients (nboost=1,988; nno-boost =994) estimated to be required
• 10 academic institutions in the US, Canada, and France contributed de-identified

patient-level data

• All patients had newly diagnosed pure DCIS (no micro-invasion), treated with

breast conserving surgery and received WBRT+/-boost

• Data were uniformly re-coded at the host institution and underwent primary and

secondary reviews prior to analysis

Results

• The final cohort consisted of 4,131 DCIS patients (nboost =2,661; nno-

boost =1,470), exceeding the sample size estimation by 39%

• Median follow-up =9 years
• Median boost dose =14 Gy
• Median age = 56.1 years
• + Margins=4%

Results

IBTR-free survival for boost vs. no boost: 97.1% vs. 96.3% 5 yrs 94.1% vs. 92.5% 10 yrs 91.6% vs. 88.0% 15 yrs (p = 0.0389)

N=4, 131

Results

• Use of boost

significant for  IBTR

• n UVA (0.013)

Characteristics HRHR P-value Boost no 1.0

• yes

0.69(0.53-0.91) <0.010 Grade I 1.0

• II/III

1.62 (1.06-2.47) 0.020 Comedo no 1.0

• yes

1.13 (0.81-1.57) 0.470 Tamoxifen no 1.0

• yes

0.60 (0.42-0.95) 0.030 Margin neg 1.0

• positive

1.79(1.05-3.05) 0.030 Age <50 1.0

• ≥50

0.57 (0.45-0.74) 0.010

MVA: Model incorporates other prognostic features

DCIS Boost/No Boost by Margin Definition Stratified by Margin Status

”Ink on tumor” (NSABP) “<2mm” (SSO/ASTRO/ASCO)

Results

Conclusions

• This series represents the largest cohort addressing the benefits of a boost in

DCIS with data from academic institutions across USA, Canada and France

• Our findings suggest that the DCIS-boost results in a small, statistically

significant, benefit in decreasing long-term IBTR across all age groups similar to that seen with invasive cancers

• For invasive cancer, the small decreases in IBTR resulted in reduced the number
• f mastectomies by ~40% for patients who had received a boost (compared with

no-boost)

• These data support the use of a boost for DCIS patients who have a life

expectancy of >10-15 years & in whom WBRT is part of the treatment plan, to provide an added incremental benefit in decreasing IBTR

ASTRO News Brie iefin ing: In Innovations in in RT Deliv livery ry

Tuesday, September 27, 1:30-2:30pm ET Moderator: Geraldine M. Jacobson, MD, MPH, MBA, FASTRO, West Virginia University

• A Phase III Randomized Trial Comparing Patient Reported Toxicity and Quality of Life (QOL)

During Pelvic IMRT as Compared to Conventional RT

Ann H. Klopp, MD, PhD, MD Anderson Cancer Center

• Radiation Boost for Ductal Carcinoma In Situ After Whole Breast Radiation Therapy (WBRT)

Improves Local Control: Analysis from Ten Pooled Academic Institutions

Meena S. Moran, MD, Yale University

• Res

esult lts of

• f COG ACNS0331: A Pha

hase II III Tria rial l of

• f In

Involv lved-Field ld Ra Radiotherapy (I (IFRT) T) and and Low Dose

• se

Cran aniospinal Irr Irradia iatio ion (LD (LD-CSI) with Che hemotherapy in n Aver erage-Ris isk Med edullo lobla lastoma: A Rep eport t from the Children’s Oncology Group

Je Jeff ff M. . Mich ichalski, i, MD, MBA, FASTRO, Washin ington Univ iversit ity in in St.

• St. Lo

Louis

Results of f COG ACNS0331: A Phase III III Trial of f In Involved-Field Radiotherapy (I (IFRT) and Lo Low Dose Craniospinal Ir Irradiation (L (LDCSI) ) wit ith Chemotherapy in in Average-Risk Medulloblastoma: : A A Report from the Children’s Oncology Group

• J. M. Michalski1, A. Janss2, G. Vezina3, A. Gajjar4, I. Pollack5, T. E. Merchant4, T. J. FitzGerald6, T. Booth7, N.
• J. Tarbell8, Y. Li4, C. A. Billups9, S. M. Perkins1, R. D. Timmerman10, J. M. Cherlow11, and R. Packer3

1Washington University School of Medicine, St. Louis, MO, 2Children's Healthcare of Atlanta, Atlanta, GA, 3Children's National

Medical Center, Washington, DC, 4St. Jude Children's Research Hospital, Memphis, TN, 5Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, 6UMass Memorial Medical Center, Worcester, MA, 7UT Southwestern/Simmons Cancer Center, Lincoln, RI,

8Massachusetts General Hospital, Boston, MA, 9St Jude Children's Research Hospital, Memphis, TN, 10University of Texas

Southwestern Medical Center, Dallas, TX, 11Long Beach Memorial Medical Center, Long Beach, CA

Background

• Largest trial conducted for average-risk (A-R) medulloblastoma
• Most common brain malignancy in children
• Aggressive tumor with a propensity to spread from the lower brain to the

upper brain and spine

• Current standard of care following surgical resection: systemic

chemotherapy + irradiation to both primary site (posterior fossa) and craniospinal axis

• Considerable negative effects on patients’ neurocognitive abilities,

endocrinologic function and hearing

ACNS0331: Tri rial Objectives

• To determine if reducing the volume of the boost from the whole

posterior fossa to the tumor bed will not compromise event-free and

• verall survival.
• To determine whether reducing the craniospinal dose of radiation

therapy from 23.4 Gy to 18 Gy in children 3-7 years of age does not compromise event-free survival and overall survival

• Endpoints included Event Free Survival (EFS) and Overall Survival (OS)

Study Schema

Children ages 3-7 Children ages 8 and older RANDOMIZE# RANDOMIZE# Low-Dose (18Gy) Craniospinal Irradiation Standard-Dose 23.4Gy Craniospinal Irradiation Involved Field RT Boost (Radiation to Tumor Bed)* Standard Volume Boost (Radiation to Whole PF) Maintenance Chemotherapy 9 Cycles

*Patients 3-7 randomized to reduced dose receive 5.4Gy to PF before IFRT #Both randomizations occur at the time of study enrollment

Medulloblastoma In Involved Fie ield RT Boost of f 54Gy

“Tumor bed”+ GTV CTV = GTV + 1.5cm Within Posterior fossa PTV=CTV + 0.3to0.5cm If 18Gy CSI dose to PF 23.4

Patient Characteristics

All l Pati tients n=513 All l Pati tients Pati tients 3-7 7 year ears of

• f

ag age IFR IFRT n=253 PF PFRT n=260 LDC LDCSI n=127 SDC SDCSI n=118 Age e on

• n stu

tudy (y (years) Median Range 8.3 3.0 – 21.8 8.2 3.0 – 19.8 8.3 3.1 – 21.8 5.9 3.2 – 7.9 5.6 3.0 – 8.0 Se Sex Male Female 329 (64%) 184 (36%) 164 (65%) 89 (35%) 165 (63%) 95 (37%) 91 (72%) 36 (28%) 74 (63%) 44 (37%) Ra Race White Black or African American Asian Native Hawaiian or Other Pacific Islander American Indian or Alaska Native Unknown 420 (82%) 41 (8%) 10 (2%) 5 (1%) 2 (0.4%) 35 (7%) 204 (81%) 23 (9%) 6 (2%) 2 (1%) 2 (1%) 16 (6%) 216 (83%) 18 (7%) 4 (2%) 3 (1%) 0 (0%) 19 (7%) 98 (77%) 11 (9%) 0 (0%) 2 (2%) 0 (0%) 16 (13%) 94 (80%) 8 (7%) 4 (3%) 3 (3%) 1 (1%) 8 (7%)

Results: Pri rimary ry Sit ite Ir Irradiation

Fiv ive e yea ear EFS es esti timates 82.2% ± 2.9% IFRT (n=227) 80.8% ± 3.0% PFRT (n=237) Fiv ive e yea ear OS es estim timates 84.1% ± 2.8% IFRT (n=227) 85.2% ± 2.6% PFRT (n=237)

Results: Craniospinal Ir Irradiation

Fiv ive e yea ear EFS es esti timates 82.6% ± 4.2% SDCSI (n=110) 72.1% ± 4.8% LDCSI (n=116) Fiv ive e yea ear OS es estim timates 85.9% ± 3.8% SDCSI (n=110) 78.1% ± 4.4% LDCSI (n=116)

Results: Local and Dis istant Fail ilure

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 2 4 6 8 10 12 Cumulative Incidence Years after Study Enrollment Cumulative Incidence of Local Failure for Eligible and Evaluable ACNS0331 Patients by RT Group IFRT PFRT

Fiv ive e yea ear ILF ILF es estim timates 1.9% ± 1.0% IFRT (n=248) 3.7% ± 1.3% PFRT (n=257)

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 2 4 6 8 10 12 Cumulative Incidence Years after Study Enrollment Cumulative Incidence of Distant Failure for Eligible and Evaluable ACNS0331 Patients 3 to 7 Years of Age by CSI Group LDCSI SDCSI

Fiv ive year IDF IDF estim timates 12.8% ± 3.2% LDCSI (n=115) 8.2% ± 2.8% SDCSI (n=109)

Conclusions

• Survival rates following reduced radiation boost volumes were

comparable to standard treatment volumes for the primary tumor site

• First trial sufficiently powered to state definitively that there is no

survival difference between the two approaches

• Reduced dose of craniospinal axis irradiation was associated with

higher event rates and worse survival

• Physi

sicia ians can adopt sm small ller boost volu lumes for r posterio ior foss ssa RT T but sh should ld mai aintain in th the standard RT T dose se for r cranio iospin inal irr irradia iatio ion

Q & A

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• ston

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Slid Slides, photos, and audio io wil ill l be avail ilable le foll llowin ing th the brie riefi fing at t www.astro.org/AMpress