news briefing plenary papers - astro

News Briefing

Plenary Papers

Monday, Sept. 23, 2013

8:30 a.m.

Bruce G. Haffty, MD, FASTRO

President-elect, ASTRO

Radiation Therapy Oncology Group 0933

Memory Preservation with

Conformal Avoidance of the Hippocampus during Whole-Brain Radiotherapy

for Patients with Brain Metastases: Primary Endpoint Results

Vinai Gondi, M.D.

Co-Director, Cadence Health Brain Tumor Center

Associate Director of Research, Cadence Health Proton Center

Chicago, IL

Co-Authors: Minesh P. Mehta, MD, Stephanie L. Pugh, PhD, Wolfgang A. Tome, PhD,

Andrew Kanner, MD, Chip Caine, PhD, Howard Rowley, MD,

Vijayananda Kundapur, MD, Jeffrey N. Greenspoon, MD, Lisa Kachnic, MD

Background

• Cranial RT associated with 4-6 month decline in

memory function

Hopkins Verbal Learning Test (HVLT): List-learning total recall

and delayed recall

• Memory function is associated with hippocampal

neurogenesis

Compartment of neural stem cells in subgranular zone of the

dentate gyrus

• Preclinical studies:

Cranial RT causes loss of hippocampal neurogenesis with

suppression of new memory formation

Hypothesis

• Conformal avoidance of the hippocampus using IMRT

during whole brain radiotherapy (HA-WBRT) for brain

metastases preserves memory function

RTOG 0933

• Phase II study of HA-WBRT

• Primary endpoint: HVLT-delayed recall at 4 months

Historical control: WBRT without hippocampal avoidance on a

prior published phase III trial

• Centralized Quality Assurance

Credentialing for HA-WBRT techniques using IMRT

o Biennial Training Workshops

o 113 physicians, 84 community, academic and international

institutions

• Real-time pre-treatment rapid review

HVLT Results

• Mean relative decline in HVLT-Delayed Recall from baseline

to 4 months: 7.0% (95% CI: -4.7 to 18.7%)

• Significant compared to historical control: 30% (p=0.0003)

0

5

10

15

20

25

30

0 2 4 6

HV

LT

Sc

ore

Months from Start of Treatment

Total Recall

Recognition

Delayed Recall

2.0% Decline

3.6% Decline 3.0% Gain

7.0% Decline

Conclusions

• Conformal avoidance of the hippocampus during WBRT

for brain metastases

Associated with memory and quality of life preservation up to 6

months follow-up

HVLT results compare favorably to historical series

• Phase II results are promising and warrant further

validation in a phase III trial

RTOG 1317: Phase III trial of PCI +/- hippocampal avoidance

for small cell lung cancer


Quality of Life (QOL) Analysis

of the Randomized Radiation (RT) Dose Escalation NSCLC Trial: “The Rest of the Story”

Benjamin Movsas, M.D. FASTRO Chairman, Dept of Radiation Oncology

Henry Ford Health System

C. Hu, J. Sloan, J.D. Bradley, V.S. Kavadi, S. Narayan, C. Robinson,

D.W. Johnson, R. Paulus, H. Choy

Supported by RTOG grant U10 CA21661 & CCOP grant U10 CA37422

from National Cancer Institute & Bristol-Myers Squibb

No conflicts of interest to disclose

Methods and Statistical Considerations

• QOL was collected prospectively via a validated lung cancer instrument:

Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) • FACT-TOI = Physical Well Being (PWB) + Functional Well Being (FWB) + Lung Cancer

Subscale (LCS)

• Data are presented here at baseline: • 3 months (from start of treatment)

• 12 months via minimal clinically meaningful changes:

• >2 points for PWB, FWB or LCS

• >5 points for TOI (per Cella et al. Clin Epidemiol 55: 285, 2002)

• Two-sample t-test, Wilcoxon-Mann-Whitney test, and/or chi-square test compared

QOL between arms and between technologies

• Effect sizes (ES) are also indicated: a moderate ES ~ 0.3-0.4

• Cox proportional hazards model used for correlating QOL and OS

• 2-sided p-values and 0.05 significance level

QOL Hypothesis

• The primary QOL hypothesis predicted for a clinically

meaningful decline (CMD) in the lung cancer subscale

(LCS) on the high-dose arm at 3 months

Change in FACT-LCS

0%

10%

20%

30%

40%

50%

3 months 12 months

46%

39%

31%36%

74 Gy

60 Gy

LC

S D

eclin

e

p=0.024

p=0.7

Results: Baseline FACTS and OS

• Beyond RT level, baseline QOL (whether PWB, FWB, or

FACT-TOI) also predicted for survival, as well as in

multivariate analysis (MVA), p=<0.02.

• Every 10 points higher on the FACT-TOI at baseline

corresponded to a 14% decreased risk of death

Results: RT Technique and QOL

• IMRT was used in 41% and 44% of QOL patients in 60Gy and 74Gy arms (p=0.6), respectively

• While this study was not randomized by technology (ie, IMRT vs 3D), there were no significant

differences in patient demographics or treatment factors between IMRT vs 3D

• With important exception that more higher stage patients (43% vs 31% stage IIIB, p=0.037) and

larger GTVs (58% vs 39% above median GTV volume, p<0.001) were treated using IMRT (vs 3D)

0%

10%

20%

30%

40%

50%

3 months 12 months

43%47%

31%

23% 3D

IMRTL

CS

De

clin

e

p= 0.06 p= 0.005

Conclusions • Despite few differences in provider-reported toxicity between arms, the

PROs tell the “rest of the story” by showing significantly worse QOL on the

high dose arm (74Gy) at 3 months, confirming the primary QOL

hypothesis.

• In RTOG 0617, baseline QOL significantly predicted for survival on MVA.

This analysis raises an intriguing question of whether the decline in QOL on the

high dose arm may help account for the survival decrement in this arm over

time.

Other factors being analyzed include heart volume irradiated, local failure

rates, etc.

• While study was not randomized to compare IMRT vs 3D, reduced

clinically meaningful decline in QOL appears to be associated with the use

of IMRT (vs 3D), suggesting that improved RT treatment techniques may

help enhance the therapeutic window for patients with lung cancer.


Phase III Trial to Evaluate the Duration of Neoadjuvant Total Androgen Suppression

and Radiation Therapy in Intermediate-Risk Prostate Cancer

Thomas M. Pisansky, MD Mayo Clinic – Rochester MN

Daniel Hunt, PhD; Leonard Gomella, MD; Mahul Amin, MD; Alexander Balogh, MD; Daniel Chinn, MD; Michael Seider, MD; Marie Duclos, MD; Seth Rosenthal, MD;

Howard Sandler, MD

8 Weeks

Androgen

Suppression

28 Weeks

Androgen

Suppression

8 Weeks

Androgen Suppression

+ External RT

8 Weeks

Androgen Suppression

+ External RT

R a n d o m i z e

16 Weeks

36 Weeks

www.rtog.org Clinical Trials 9910

752 pts

738 pts

Neoadjuvant Androgen Suppression Duration Trial Design

Intermediate Risk Prostate

Cancer

• Tumor Stage

• Gleason Score

• Serum PSA

Neoadjuvant Androgen Suppression Duration Outcomes

Disease-Specific Survival

Year after randomization

Dis

ea

se

-spe

cific

su

rviv

al (%

)

Patients at risk 8-week AS 752 725 690 677 639 609 569 531 474 350 28-week AS 737 718 686 664 642 610 582 539 456 307

Events 8-week AS 30 28-week AS 24 P=0.45

98%

99%

95%

96%

HR=0.81 (0.48-1.39)


Bio

ch

em

ica

l fa

ilure

(%

)


Events 8-week AS 192 28-week AS 185 P=0.78

16%

19%

27%

27%

Biochemical Failure – Phoenix

Median follow-up: • 8.7 yrs (0-12.4) all

patients • 9.3 yrs (0-12.4) for

survivors

Death due to prostate cancer: • 3% of all patients • 12% of all deaths

Definition: PSA nadir + 2 ng/mL • Example: Pretherapy PSA=10 falls to 0.1=nadir

rises to 2.1=biochemical failure

Neoadjuvant Androgen Suppression Duration Cancer Recurrence

LocoRegional Progression Distant Metastasis

LocoRegional tumor control • 5-yr = 96% vs. 98% (28-week) • 10-yr = 94% vs. 96% (28-week) Progression w/o biochemical failure • 10-yr = 1%

Metastasis-free • 5-yr = 97% vs. 97% (28-week) • 10-yr = 94% vs. 94% (28-week) Progression w/o biochemical failure • 10-yr = 1%


Lo

co

reg

ion

al

pro

gre

ssio

n (

%)


Events

8-week AS 42

28-week AS 27 P=0.07

2% 4%


Dis

tan

t m

eta

sta

sis

(%)


Events

8-week AS 38

28-week AS 40 P=0.80

3% 3%

4%

6% 6%

6%

Intermediate-Risk Prostate Cancer Conclusions

• Neoadjuvant androgen suppression = 8 weeks

• Neoadjuvant + concurrent androgen suppression = 16-wks

• Short-term androgen suppression + external beam RT

excellent long-term outcomes

• The chance of dying of prostate cancer in the decade after

treatment = 5%

• Results confirm our prior study (9408)

• Results are reproducible men with intermediate-risk

prostate cancer know what to expect with this treatment

Intermediate-Risk Prostate Cancer Conclusions (continued)

• Little room for improvement in disease-specific survival

(and overall survival, also) studies to prove further

benefit will be difficult

• Focus of future research:

Shift focus away from survival outcomes (as has happened

in breast cancer)

Decrease biochemical failure decrease secondary

therapy established ideal RT dose

Decrease side-effects intensity-modulation and image-

guidance


Two Item Questionnaire Effectively Screens

for Depression in Cancer Patients

Receiving Radiotherapy

Small, W; Pugh, S; Wagner, L; Kirshner, J; Sidhu, K; Bury, M;

DeNittis, A; Alpert, T; Tran, B; Bruner, D

Methods

• Radiotherapy patients underwent multiple screening

questionnaires.

• Patients who were identified as screening positive for

depression were to receive a Structured Clinical

Interview for Diagnosis DSM-IV (SCID) Mood Disorder

module by phone.

• A sample of patients screening negative also underwent

a telephone interview.

Results

• 463 patients were accrued from May 2009 – March 2011,

averaging 57.7 patients/month.

• Of the screening questionnaires tested, a simple two

question screen, Patient Health Questionnaire-2 (PHQ-2),

was found to be the most accurate.

PHQ-2 Questions

• A cut-off score > 3 is positive

Over the last 2

weeks how often

have you been

bothered by any of

the following

problems?

Not at all Several

days

More than

half the

days

Nearly

every day

Little interest or

pleasure in doing

things 0 1 2 3

Feeling down,

depressed, or

hopeless

0 1 2 3

Conclusions

• The PHQ-2 demonstrated psychometric properties

equivalent to the PHQ-9 and superior to HSCL-25 and

NCCN-DT.

• This simple two item screening instrument may be used

as a standard for care for the assessment of depression

in cancer patients receiving radiation.

For additional questions or interviews, please contact the

ASTRO Press Office:

404-222-5303 or 404-222-5304 Michelle Kirkwood, [email protected] Nancy Mayes, [email protected]

mailto:[email protected]

mailto:[email protected]

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