Aspects of cancer related lymphoedema Vaughan Keeley Derby UK Dublin, Sept 2014

Aspects of cancer related lymphoedema What causes it? How can we detect it early? Can it be prevented? The problem of cellulitis Lymphoedema in head and neck cancer Surgery for lymphoedema

What causes lymphoedema after cancer treatment? Most studies have involved breast cancer related lymphoedema (BCRL) Ideas are changing

How common is BCRL? Overall 21.4% 18.9% by 2yr 5.6% after sentinel node biopsy (SNB) 19.9% after axillary node clearance (ANC) (Disipio et al 2013) BUT... difficulty with definitions and length of follow-up.

Defining lymphoedema Difficulty defining early lymphoedema

Diagnostic criteria for BCRL 10% difference between limbs, 200ml difference between limbs, 2cm difference circumferential measurements 10% change from baseline >3% change from baseline (sub-clinical) Patient reported symptoms (swelling, heaviness)

Incidence at 30 months by definition 200ml diff 67 (58-76) % 10% diff 45 (33-59) % 2cm circ diff 91 (84-96) % Swelling / heaviness 41 (31-54) % (Armer, 2009)

Risk factors for BCRL Strong evidence for: Extensive surgery (ANC; greater no. of LNs removed; mastectomy) Overweight / obesity (Disipio, 2013)

Other possible risk factors for BCRL Radiotherapy Drain, wound or infection complications Cording Seroma formation Taxane chemotherapy Skin puncture. Oestrogen receptor negative cancers?

What causes BCRL? “Conventional model” Destruction of lymphatics / lymph nodes by treatment Obstructive lymphoedema

But.... 6% women develop BCRL after SNB alone. 80% of women don’t develop BCRL after ANC BCRL takes months/years to develop Distribution is not uniform

Research observations: Local lymph flow  when oedema present   pumping pressure in lymphatics in established BCRL

Study of breast cancer patients followed at 7m and 30m at 7m there was no impairment of lymph drainage if no swelling. those destined to develop lymphoedema had highest lymph flow in muscle + subcutis lymph flow was also  in the other (unoperated side) arm

Conclusions This suggests a constitutional predisposition (both arms affected) A possible genetic effect The high lymph flow may lead to damage to the lymph vessels over time and therefore the flow will reduce and swelling develop (delayed onset)

Early detection and prevention It is evident that early mild lymphoedema is easier to treat than advanced lymphoedema with fat / fibrosis How early can it be detected? Can it be prevented?

Early detection 1 By limb volume measurement: - comparison with pre-op measurements - sensitive method eg Perometry - “subclinical” swelling (3% change?) - early intervention reduces swelling (and possibly prevents progression?) (Stout, 2008)

Early detection 2 By bioimpedance spectroscopy - measures fluid changes in the tissues (the first stage of swelling) - evidence that this may detect lymphoedema months before a volume change is measured

BEA Multi-frequency Bioimpedance in the Early Detection of Lymphoedema after Axillary Surgery - a multicentre study in UK examining whether BIS can detect BCRL before changes in limb volume (by Perometer) after ANC - aim – n=1100 - recruitment to date = 1016 (Derby = 280)

BEA – early results n=556 Lymphoedema defined as 10% change in relative arm volume (RAVC) Incidence at 12m = 13.7%; at 24m = 25.0% Predictive factors: ER neg; no. of positive nodes; RAVC at 6m >= 5%-<10%

Limitations of these methods At present, both Perometry and BIS do not measure hand swelling well Localised swelling may develop which is “diluted” by whole limb measurements Differential swelling - may be detectable with segmental BIS or Perometry; new methods being developed

The benefit of pre-operative measurements May facilitate early detection May help identify high risk groups / consider introduction of preventative measures

Prevention? Can the incidence of lymphoedema be reduced / condition prevented? - change in surgical / RT methods? - exercise? - MLD? - compression? - precautions incl weight management?

Change in Surgery / RT? SNB associated with lower incidence of BCRL than ANC RT method changes - ? effect (NB more breast oedema since WLE + RT)

Exercise Exercise programmes may help to reduce incidence (Box et al 2002; Torres Lacomba et al 2010) Changing advice on exercise of “at risk” arm.

MLD (manual lymphatic drainage) Mixed evidence: - no effect (Devoogdt et al 2011) - positive effect (Zimmermann et al 2012)

Compression Possible effect of preventing progression of subclinical lymphoedema by wearing a compression sleeve for 1 month (Stout, 2008) Current UK study in progress: PLACE

PLACE Prevention of Lymphoedema after Axillary Clearance by early External Compression. An RCT of the use of a compression garment for 1 year v standard care / precautions in women with a 4-8% increase in arm volume (Perometry) by 9 months post-ANC Outcome measure – lymphoedema in each group at 1 year and 18months after randomisation Early treatment or prevention?

Progress with PLACE Slow recruitment Fewer women than predicted reached threshold changes in RAVC Currently expanding to those who have only had SNB Local recruitment = 22 (total = approx 80)

Genetic predisposition A number of candidate genes Samples being collected as part of BEA study.

Precautionary measures Avoid injuries including cuts and abrasions, for example, wear gloves when gardening Use a thimble when sewing Use an oven glove when cooking Take care when ironing Avoid tight clothing including tight bra straps

Precautionary measures 2 Avoid irritating cosmetics/soaps Avoid sunburn Avoid insect bites/cat scratches Use an electric razor for shaving Avoid obesity

Precautionary measures 3 Avoid injections or venipuncture in the “at risk” arm Avoid blood pressure measurement in the “at risk” arm Seek medical advice if “at risk” arm becomes inflamed or swollen

Breast lymphoedema Increasingly recognised following WLE and radiotherapy Difficult to measure Clinical diagnosis Treatment – MLD / compression / taping etc More research required.

Cellulitis and lymphoedema

What is cellulitis? also called erysipelas, acute inflammatory episodes etc. bacterial infection of skin + tissues under skin more common in people with lymphoedema / recurrent

Why are people with lymphedema prone to cellulitis? Lymph nodes / lymph vessels are part of the immune system – fighting infection In lymphoedema the local immune system is less effective

Why are people with lymphedema prone to cellulitis? Lymph nodes / lymph vessels are part of the immune system – fighting infection In lymphoedema the local immune system is less effective

Is it definitely cellulitis? features as above no specific tests some tests may be helpful:- white blood cell count CRP (C-reactive protein) swabs for culture

What else can it be? raised venous pressure deep vein thrombosis eczema / dermatitis contact sensitivity etc

Which bacteria cause it? Not entirely clear Beta haemolytic Streptococci Staphylococcus aureus ? others (e.g. in genital cellulitis)

How is it treated? Antibiotics – oral / intravenous Remove compression – temporarily Pain relief - Paracetamol - avoid non-steroidal anti-inflammatories (e.g. ibuprofen) Rest

Which antibiotics? BLS / LSN Consensus guidelines www.thebls.com www.lymphoedema.org evidence of best treatment is lacking

Antibiotics at home: (oral): Amoxicillin 500 mg three times a day for at least 2 weeks Flucloxacillin is an alternative

Antibiotics in hospital: (intravenous): if v. unwell, low blood pressure etc or getting worse on oral antibiotics Flucloxacillin 1 g every 6 hrs until temperature normal etc. then oral

What may cause an episode of cellulitis? Broken skin - cuts - insect bites - Athlete’s foot / fungal infection - eczema / dermatitis - ulcers - ingrowing toenail Others - ? sore throat - ? stress

Recurrent cellulitis UK survey - 396 patients with lymphoedema and cellulitis - 76% had previous episodes of cellulitis - average 1.8 episodes in previous year

Why is this a problem? acute cellulitis – unpleasant, may need hospital admission; loss of time at work etc. cellulitis damages lymph vessels making lymphoedema worse

How can I reduce the chance of getting cellulitis? Skin care Control of swelling

Precautions - insect repellent - antiseptic creams for cuts - treat dermatitis, ingrowing toenail, Athlete’s foot etc - avoid cuts e.g. gloves when gardening, avoid bare feet in garden

Prophylactic antibiotics? - if 2 or more episodes of cellulitis in 1 yr. - address risk factors - control swelling - Phenoxymethylpenicillin (1 year to begin with)

Frequently asked questions Q: How soon after infection should I wear my compression garment again? A: As soon as is comfortable. If broken skin, may need bandage / dressings

Q: Should I keep a course of antibiotics at home, in case I get cellulitis? A: This may be advisable if you have repeated episodes and a familiar pattern, especially if foreign travel.

Thank you!