Dott. Carlo Garufi Oncologia Medica C Istituto Regina Elena, Roma Scuola Mediterranea di Oncologia...
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Transcript of Dott. Carlo Garufi Oncologia Medica C Istituto Regina Elena, Roma Scuola Mediterranea di Oncologia...
Dott. Carlo Garufi Oncologia Medica CIstituto Regina Elena, Roma
Scuola Mediterranea di Oncologia
“Actigrafia nel tumore della mammella”
Roma 28.11.2008
BREAST CANCER
• Fatigue is the most prevalent and distressing symptom experienced by pts receiving adjuvant ChT for early stage BC
• Higher fatigue levels are related to sleep maintenance problems and low daytime activity in pts after ChT
• Sparse data available about circadiam rhythms alteration and fatigue prior to chemotherapy
Ample evidence suggest doctors might systematically misjudge patients' perception levels of symptoms or related important aspects of their illness….and there is wide agreement that patient themselves should be the primary
source of information. (Slevin et al 1988; Sprangers et al. 1992; Da Silva et al. 1996; Stephens et al. 1997 Passik et al. 1998; Fayers et al. 2000; Wilson et al. 2000; Titzer et al. 2001)
http://www.ispor.org/Meetings/va0502/symposium.asp
Is the doctor’s view a reliable measure of patients HRQOL?
Cancer Related Fatigue
“distressing, persistent, subjective, sense of tiredness or exhaustion related to cancer or to cancer treatment that is not proportional to recent activity and interferes with usual functioning”
NCCN 2006
(Cleeland, et al, 2004)
Anxiety
Pain
Lower sleep quality
Physical InactivityPoor PS
Cancer Related Fatigue
REST/ACTIVITY RHYTHM: THE ACTIGRAPH
Piezo-electric accelerometer;
Number of wrist accel./minute;
Allows continuous recording, over a long time period.
Parameters: 24-h pattern and
alternance of rest and activity.
Independent prognostic value of the rest/activity circadian rhythm on overall survival (OS) in patients (pts) with metastatic colorectal cancer (MCC) receiving first line chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin: a companion study to EORTC 05963. C. Garufi et al. ASCO 2005
The data confirmed the strong and indipendent prognostic value of the RAR for the survival of MCC patients in a multicentre randomized trial
Quality of life (QoL) correlates with the rest/activity circadian rhythm (RAR) in patients (pts) with metastatic colorectal cancer (MCC) on first line chemotherapy with 5-fluorouracil, leucovorin and oxaliplatin : an international multicenter study (EORTC 05963). P.F. Innominato et al. ASCO 2005
The correlation between RAR and Global QoL and symptom scores as fatigue and anorexia was confirmed for the first time in a multicenter setting
5FU/FA5FU/FA FFLFFL Garufi et al Anticancer Drugs ‘01Garufi et al Anticancer Drugs ‘01
CPT-11 + FF CPT-11 + FF 5-165-16
Garufi et al Cancer ‘01Garufi et al Cancer ‘01
EORTC 05011 EORTC 05011 CPT-11CPT-11 + FFL + FFL
5FU/FA5FU/FA Garufi et alGarufi et al
EJC ‘97EJC ‘97
Studi di Cronotherapia presso l’IREStudi di Cronotherapia presso l’IRE
CPT-11 CPT-11 bolus + FFL cronobolus + FFL crono Garufi et al BJC ‘03Garufi et al BJC ‘03
CPT-11 crono vs CPT-11 crono vs standard + FF standard + FF 4-104-10
Garufi et al EJC ’06 Garufi et al EJC ’06
Variables Hazard ratio (HR) 95% Confidence Interval P-value
UNIVARIATE
Sex 0.677 0.462-0.991 0.04
Performance Status 0.277 0.163-0.469 <0.0001
Age n.s.
Site of primary tumor n.s
Number site involved 0.605 0.402-0.911 0.01
Qol parameters
Physical Functionig 0.988 0.979-0.996 0.004
Emotional Functioning 0.99 0.982-0.998 0.01
Social Functioning 0.992 0.923-1.000 0.04
Fatigue 1.014 1.007-1.021 <0.0001
Pain 1.011 1.004-1.018 0.002
Nausea/vomiting n.s.
Appetite Loss 1.007 1.000-1.014 0.04
Costipation n.s.
Diarrhoea n.s.
Global QoL 0.978 0.970-0.986 <0.0001
MULTIVARIATE
Performance Status 0.387 0.221-0.677 <0.0001
Global QoL 0.977 0.969-0.986 <0.0001
Analisi Univariata e Multivariata sec Cox per la Sopravvivenza
Individual patient circadian rhythmassessment by actigraphy.
Cortisol Ratio (Slope)
Serum TGF-
Serum IL-6
Symptoms
Robust Rhythm *(autocorrelation >0.47)
1.72(Steep)
Low Low Less fatigue, appetite loss.
Dampened Rhythm(autocorrelation <0.35)
1.60(Flat)
High High More fatigue and appetite loss.
* p = < 0.05
Correlation: Rest/activity and Cortisol rhythms,TGF- and cytokines, and symptoms.
Clin Cancer Res 2005; 11(5):1757-1764
Study Population Study timing Variable Methods Findings
Ancoli-Israel 2006
n=85 (34-79y)
Stage I-IIIPrior ChT Fatigue
Obj/Subj sleep quality
Circadian rhythm
MFSI, PSQI Actigraph
Significant correlation (p>.0001) between subjective measure of sleep
and fatigue
Andrykowski 1998
n=88 (35-76y)
Stage I-IIIAAfter ChT Fatigue
Sleep quality
CFS, PFS, PSQI Significant correlation between fatigue and sleep quality
Berger
1998
n=72 (33-69y)
Stage I/IIDuring ChT Fatigue
Activity and rest cycle
PFS
Actigraph
Fatigue and disrupted activity/sleep inversely related (p<.05)
Berger
1999
n=72 (33-69y)
Stage I/IIDuring ChT Fatigue
Circadian activity/rest indicators
PFS
Actigraph
Reduced daytime activity, increased daytime sleep, and increase nighttime
awakening were associated with increased fatigue
Berger
2000
n=14 (32-69y)
Stage I/IIDuring/ after ChT Fatigue
Activity and rest cycle
Actigraph, MSD, SES, PFS
Low activity, disrupted sleep and increased distress werecorrelated with fatigue
Bower
2000
n=1957 (mean 55y) Stage 0-III
After ChT Fatigue
Sleep disturbance
Energy fatigue subscale MOSSS
Fatigue is strongly associated with sleep disturbance
Broeckel 1998
n=61 (29-75y) After ChT Fatigue
Sleep quality
FS from PMS, PSQI
Severe fatigue significantly correlates with poorer sleep quality (p<.05) and sleeping during the day (p<.001)
Curran
2004
n=25 (28-63y)
Stage 0-IIIAfter ChT Fatigue
Sleep duration
Likert scale, diary sleep duration
Fatigue after treatmento not correlates with sleep duration
Jacobsen 1999
n=54 (28-77y) stage I-III
During ChT Fatigue
Sleep problems
MSAS Sleep problems associated with significant increase in fatigue severity
Okuyama 2000
n=134 (28-86y)
Stage 0-III
After surg, ChT, RT
Fatigue
Sleep
CFS, Likert scale Insufficient sleep is one of the determinat of fatigue
Roscoe
2002
n=78 (34-79y) During Cht Fatigue
Circadian sleep rhythm
FSC
Actigraph
Increased circadian rhythms disruption correlates with increased fatigue
• 85 women with stage I-IIIA breast cancer
• evaluation 7 days prior adjuv (n=72) or neoadjuv (n=13) ChT
Women report fatigue and disturbed sleep before ChT begins
Significant relationship between subjective poor sleep and fatigue and/or reduction of functional outcome
Objective measures confirm disrupted and disturbed sleep
However no significant correlation between objective sleep variable at night or during the day and fatigue and/or functional outcome
Although their circadian rhythms are robust, pts with more delayed rhythms experience more daily disfunction secondary to fatigue
Possible correlation between depression and fatigue Supp Care Cancer 2006, 12: 201-9
• 219 women with stage I-IIIA breast cancer• Evaluation 48 h prior adjuvant ChT• Measure of sleep (PSQI), fatigue (PFS) and circadian rhythms
(Actigraph)
J Pain Sympt Manag 2007, 33: 398-409
Berger et al., J Pain Sympt Manag 2007
Change in the actigraphy measures over time were significantly correlated with chenges in fatigue, mood, and depression
Supp Care Cancer 2002, 10: 329-336
Circadian rhythm
Fatigue
Depression
Mood
Roscoe et al., Supp Care Cancer 2002
Conclusions
• Fatigue correlates with sleep distrubance
• Actigraph can be used to monitor circadian rhythms alteration
• Strategy of intervention through light exposure or phisical activity could help in preventing CRF