Discussion Panel on Quality of Life and Radiotherapy in Head and Neck Cancer Volker Budach, MD, PhD Head Department for Radiation Oncology Charité Campus-Mitte Berlin Interdisciplinary Workshop on Modern Treatment Options Statements on Head and Neck Caner Frankfurt, 27-28 of January 2006
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V. Budach – Statements on H&N Cancer - 1 Discussion Panel on Quality of Life and Radiotherapy in Head and Neck Cancer Volker Budach, MD, PhD Head Department.
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V. Budach – Statements on H&N Cancer - 1
Discussion Panel on Quality of Life and Radiotherapy in Head and Neck Cancer
Volker Budach, MD, PhD Head Department
for Radiation OncologyCharité Campus-Mitte
Berlin
Interdisciplinary Workshop on Modern Treatment Options
Statements on Head and Neck CanerFrankfurt, 27-28 of January 2006
V. Budach – Statements on H&N Cancer - 2
Most of the studies addressing chemoradiation of locally advanced H&N cancer report increased acute and in some instances also late morbidities!
Is this a valid observation which can be supported by published literature results?
Are the data sufficient to address this question?
Quality of Life Issues and Acute Toxicity/Late Morbidity Items in Chemoradiation of Locally
Advanced Head and Neck Cancer
V. Budach – Statements on H&N Cancer - 3
Toxicity in random. head & neck trials: RT vs. RT-CHX(grade >=III)
Concurrent RT-CHX (“older studies“)drug(s) %-diff. n end point referenceBLM +54.0%* 199 acute Eschwege et al. 1987
BLM/MTX +50.0%* 96 acute Fu et al. 1987
MTX +9.0%* 313 acute Gupta et al. 1990
5-FU +11.7%* 282 acute Sanchiz et al. 1990
5-FU +20.5%* 175 acute Bowman et al. 1994
mean +23.7% 1065 acute
5-FU grade 4:+4.4% 136 late Collin et al. 1972 BLM/MTX +5.0% 96 late Fu et al. 1987MTX “not enhanced“ 313 late Gupta et al. 1990
*= significantly more pat. with severe mucosa and/or skin toxicityW. Budach, personell communicationW. Budach, personell communication
V. Budach – Statements on H&N Cancer - 4
Toxicity in random. head & neck. trials: RT vs. RT-CHX(Concurrent RT-CHX: grade >=III)
drug(s) %-diff. n end point referenceMMC (adj) +0.2% 113 acute Haffty et al. 1983MMC -12.0% 117 acute Weissberg et al. 1989
P/5-FU +22.0%* 270 acute Wendt et al. 1998P-P/5-F +9.2% 147 acute Al-Sarraf et al. 1998
P/5-FU +30.0%* 222 acute Calais et al. 1999P (daily) +13.8% 130 acute Jeremic et al. 2000
mean +16.6% 999 acute
MMC +2.0% 117 late Weissberg et al. 1989P/5-FU +3.6% 270 late Wendt et al. 1998
P/5-FU +12.0%** 222 late Calais et al. 1999P (daily) +17.0% 130 late Jeremic et al. 2000
mean +8.2% 739 late *= significantly more pat. with severe mucosa and/or skin toxicity
**= significantly more severe late toxicityW. Budach, personell communicationW. Budach, personell communication
V. Budach – Statements on H&N Cancer - 5
Toxicity in random. head & neck. trials: RT vs. RT-CHX(Concurrent or alternating RT-CHX: grade >=III)
Studies with 5-14% less RT-dose in CHX-arm RT dose end
drug(s) with CHX %-diff. n point referenceP/5-FU alt. -14% -2.5% 157 acute Merlano et al. 1991P/5-FU -5% -2.0% 116 acute Brizel et al. 1998MMC/5-FU -10% -9.5%* 384 acute Budach et al. 2000
mean -5.2% 774 acute
P/5-FU alt. -14% -9.1%** 157 late Merlano et al. 1991 P/5-FU -5% +2.0% 116 late Brizel et al. 1998
MMC/5-FU -10% -3.8% 384 late Budach et al. 2000
mean -3.1% 774 late
*= significantly less pat. with severe mucosa toxicity **= significantly less severe late toxicity
W. Budach, personell communicationW. Budach, personell communication
V. Budach – Statements on H&N Cancer - 6
No Correlation between acute and late CHX excess toxicity (Evidence from 18 randomized clinical trials)
NSCLC
Head&Neck-Ca. Cervical-Ca. Rectal-Ca.
R2 = 0.074-10
-5
0
5
10
15
20
-20 0 20 40 60
excess acute >=grade III toxicity [%]
exce
ss la
te >
=g
r. II
I to
xcit
y [%
]
W. Budach, personell communicationW. Budach, personell communication
V. Budach – Statements on H&N Cancer - 7
Developments in Safety, Toxicity and QOL Reporting
in Oncology Clinical Trials
Dimtrios Colevas MDSenior Investigator,Investigational Drug
Branch, CTEP, National Cancer InstituteBethesda, MD
Andy Trotti MDAndy Trotti MDDirector of Clinical Trials,Director of Clinical Trials,
Radiation OncologyRadiation OncologyH. Lee Moffitt Cancer H. Lee Moffitt Cancer
CenterCenterTampa, FLTampa, FL
Deborah Watkins-Bruner RN PhD
Director of Outcomes Research, Fox Chase Cancer Center
Philadelphia, PA
V. Budach – Statements on H&N Cancer - 9
• Provide background on how safety data is generated, analyzed and published.
•We will highlight areas in need of better methods, standards and guidelines in patient screening/data collection, data analysis, presentation, publication, and interpretation.
•Target audience: Primarily directed at the investigator (or the practitioner with a keen interest in toxicity/QOL) who wants to have a deeper understanding of toxicity profiles and QOL outcomes.
•Highlight opportunities for research questions.
Objectives
Research opportunity…
V. Budach – Statements on H&N Cancer - 10
•Understand the strengths and limitations of the current toxicity reporting process for multimodality clinical trials
•Understand changes in the new NCI-Common Terminology Criteria system for adverse events (CTCAE)
•Understand the role of QOL and symptom tools in specific investigations of adverse effects
Educational Objectives
V. Budach – Statements on H&N Cancer - 11
References and Sources
Adverse Effects of Cancer Treatment:
Metrics, Management and Investigations
Seminars Radiation Oncology
Volume 13, No 3, July 2003
Andy Trotti MDAndy Trotti MDDirector of Clinical Trials,Director of Clinical Trials,
Radiation OncologyRadiation OncologyH. Lee Moffitt Cancer CenterH. Lee Moffitt Cancer Center
Tampa, FLTampa, FL
V. Budach – Statements on H&N Cancer - 15
How should we evaluate the adverse effects of
cancer treatment on health status in oncology?
V. Budach – Statements on H&N Cancer - 16
Patient Relevance
Sp
ecif
icit
y
* Bentzen et al (Sem Rad Onc July 03)* Bentzen et al (Sem Rad Onc July 03)
Adverse Effects Domains*
ANALYTIC (Lab)
SYMPTOMS
OBJECTIVE (Exam)
QUALITY OF LIFE &PATIENT REPORTED OUTCOMES
Common Toxicity Criteria
Research opportunity:Develop and use PROsto improve quality of symptom capture.
V. Budach – Statements on H&N Cancer - 17
•QOL and symptoms scales are wholly subjective metrics--a highly
individual personal perception.
•QOL scores are affected by one’s ability to cope/adapt to adversity
•QOL scores are influenced by cancer status
•QOL correlates with toxicity in some studies, not in others
•QOL may include diverse domains of social support, spirituality
QOL = Toxicity
•QOL (assessed by patients) may be complimentary to, and may
help to inform the clinician about adverse effects, but is
not a substitute for adverse event reporting (as assessed by
clinicians).
V. Budach – Statements on H&N Cancer - 24
Safety
Efficacy
Balancing Risk and Benefit
This gap constrains our ability to make informed judgments about the balance of risks and benefits.
**Locally advanced H&N-cancer of the oral cavity, oro- and hypopharynx stratified Locally advanced H&N-cancer of the oral cavity, oro- and hypopharynx stratified according to centres, tumor sites, N-stage and gradingaccording to centres, tumor sites, N-stage and grading
V. Budach – Statements on H&N Cancer - 74
T2 1 21 5 27
T3 5 15 46 3 69
T4 14 17 207 44 282
T1 3 3 6
Total
Stage III: 5.5% (n=21)Stage IV: 94.5% (n=363)
N0 TotalN1 N2 N3
TNM-Matrix
19 33 277 55 384
Multicentric Phase-III Trial “Accelerated Hyperfractionation ± 5-Fluorouracil / Mitomycin C
for locally advanced head & neck cancer (ARO 95-6)
V. Budach – Statements on H&N Cancer - 75
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60
Month from Entry
Lo
core
gio
na
l Co
ntr
ol
Numberat risk
Numberat risk
Numberat risk
Numberat risk
Numberat risk
Sum ofeventsSum ofeventsSum ofeventsSum ofeventsSum ofevents
188 118 82 67 60 37
50 69 75 77 78
193 89 63 50 45 32
75 96 100 102 102
Arm B - CRT
Arm A - RT
p=0.004(early) p=0.002(late)
ARO 95-06
V. Budach – Statements on H&N Cancer - 76
0.0
0.2
0.4
0.6
0.8
1.0
0 12 24 36 48 60
Month from Entry
Ove
rall
Surv
iva
l
Numberat risk
Numberat risk
Numberat risk
Numberat risk
Numberat risk
Sum ofeventsSum ofeventsSum ofeventsSum ofeventsSum ofevents