BROOKLYN 2 RADIOTHERAPY Patries HERST Sat 31 st Aug 2013 Session 1 / Talk 1 09:20 – 09:46 ABSTRACT Purpose. Acute radiation-induced cystitis is a common.

BROOKLYN 2

RADIOTHERAPY

Patries HERST

Sat 31st Aug 2013

Session 1 / Talk 1

09:20 – 09:46

ABSTRACTPurpose. Acute radiation-induced cystitis is a common side effect of radiation therapy to the pelvis, with up to 40% of prostate cancer patients suffering from cystitis to some extent. Currently there is no effective treatment for radiation cystitis. Here we investigate the effect of cranberry capsules on the extent of radiation-induced cystitis in prostate cancer patients in a double blinded RCT.Methods and materials. A total of 40 men receiving radiation therapy for prostate cancer at the Department of Radiation Therapy in Dunedin Hospital participated in this trial; 20 men were randomized to the cranberry arm and 20 were randomized to the placebo arm. The men took one capsule a day during breakfast from the first day of treatment for 70 days. Patients, clinicians and research assistants were blinded to the content of the capsules. Severity of cystitis was assessed using the modified urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) scale. Items include severity of symptoms (pain, blood in urine, urinary frequency during day or night, leakage, use of pads and URAL sachets) as well as their effect on daily life.Results. Cranberry capsules significantly decreased the level of pain associated with acute radiation cystitis but did not affect the other EPIC measures.

Cranberry capsulesfor Radiation cystitis: a pilot RCT

Katelin Hamilton, Noelle Bennett, Patries Herst*

August 2013

Radiation cystitis in 60-90% of prostate patients

Damage to the lining of the bladder wall

seepage of acidic urine into the underlying tissues

inflammation, compromised detrussor muscle functioning

Symptoms similar to UTIs without infection:

Pain/Burning Weak stream, incomplete emptying Poor control, leakage, dripping Urgency

Background

TreatmentCurrently no standard treatment to prevent or decrease the severity of radiation cystitis

URAL treats the symptoms but not the inflammation

Cranberries reduce the incidence of UTIs in young women (Cochrane review in 2009)

Anecdotally, cranberry capsules seemed to reduce radiation cystitis in Dunedin patients

Campbell et al (2003) randomized unblinded comparison between cranberry juice and apple juice in 112 men with prostate cancerNo significant difference between study arms

Cowan et al (2012) placebo-controlled, double blinded trial of cranberry juice and placebo in 128 women with uterine/bladder cancer.Trend for decrease in urinary symptoms but not significant

HypothesisCranberry capsules are superior to placebo in decreasing the severity of radiation cystitis.

Bonetta and Pierro (2012)

standardized enteric coated cranberry tablets against nothing on radiation cystitis in 370 prostate cancer patients

Decreased levels of pain, urgency and day and night time frequencies (p<0.01)

Not blinded, randomization unclear

Take home message

Use standardized capsules

Use placebo capsules for double blinding

Be aware of compliance issues

Informed Consent

Randomization

Cranberry Capsules Placebo Capsules

1 Capsule a day for 10 weeks

1. Severity of cystitis2. URAL usage

CT Scan

Start RT

2 weeks after RT completion

Eligibility

•IMRT for prostate cancer•No previous RT to pelvis•No systemic disease•Karnofski score>70

Assessment

Modified EPIC: 2x week during and 1x week for 4 weeks after tmt

Protocol: Stage II RCT: 40 patients

Measurements: EPIC

Expanded Prostate Index Composite: Urinary Domain: both symptoms AND effect on QoL

Scores were taken 2x a week, subtracted from baseline score and averaged over the number of assessments to give average increase in EPIC scores for each patient

Patients scores are averaged to give average increase in EPIC scores for each cohort

Randomized41

Cranberry Capsules21

Placebo Capsules20

Non-Compliance1

Non-Compliance1

Cranberry Completed20

Placebo Completed19

Participants for Analysis39

Symptoms

In the last few days have you had:

Pain: how often: “never” to “more than once a day” Leakage: how often: “never” to “more than once a day”Control: total to none whatsoeverPads: how many: “none” to “more than 2”URAL: how often: “rarely” to “more than once a day”Blood: how often: “rarely” to “more than once a day”

Symptomsn=20n=19

0.03

P value

pain 0.03

leakage 0.14

control 0.94

pads 0.49

URAL 0.54

blood 0.85

No cystitis : 10/39 (26%)Cranberries: 7/20 (35%)Placebos: 3/19 (16%)

Ave

rag

e In

crea

se in

EP

IC S

core

Quality of Life

From “no bother at all” to “big problem”,

how much bother have the following been:

Pain/burning upon urinationDripping/leakingWeak stream/incomplete emptyingDay time frequencyNight time frequency (nocturia)Blood in urineOverall

P value

pain 0.04

leakage 0.67

weak stream 0.68

frequency 0.49

nocturia 0.12

blood 0.72

overall 0.64

Quality of Life

0.04

n=20n=19

No bother: 4/39 (10%)Cranberries: 4/20 (20%)Placebos: 0/19 (0%)

Ave

rag

e In

crea

se in

EP

IC S

core

Major Confounder

Over-hydration (‘full bladder syndrome”)

14 patients had high hydration levels (8 cranberries, 6 controls)

25 patients had low hydration levels (12 cranberries, 13 controls)

n=14n=25

0.01

P value

pain 0.52

leakage 0.31

control 0.33

pads 0.25

URAL 0.01

blood 0.10

SymptomsA

vera

ge

Incr

ease

in E

PIC

Sco

re

Inconsistent advice

P value

pain 0.93

leakage 0.22

weak stream 0.56

frequency 0.31

nocturia 0.27

blood 0.27

overall 0.08

Quality of Lifen=14n=25

Ave

rag

e In

crea

se in

EP

IC S

core

Other possible confounders

High baseline cystitis scores

19/39 (49%) men had baseline scores >1 for at least one of the measures

Increase from baseline is highest if baseline is 0 (0-4), compared with 1 (0-3) or 2 (0-2) or 3 (0-1) or 4 (0)

12 men on placebo capsules and 7 men on cranberry capsules had high baseline scores. Placebo results likely to be artificially low.

Inconsistent advice regarding URAL usage

Conclusion

Cranberry capsules may decrease certain aspects of radiation cystitis.

NextLarge multicentre RCT in NZ

Standardized capsules, placebo capsules

Exclude men with high baseline scores

Consistent hydration levels

URAL given only when symptoms reach 2

Trial Participants

Staff from Southern DHB

Funding:

Acknowledgements