BREAST CANCER CONCERNS AND TREATMENTS. A/Prof Martin Borg Adelaide Radiotherapy Centre

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1 BREAST CANCER CONCERNS AND TREATMENTS A/Prof Martin Borg Adelaide Radiotherapy Centre

2 Breast Conserving Cancer Treatment Breast Cancer A Multidisciplinary Approach Surgery Radiotherapy (RT) Chemotherapy (CT) Hormone Therapy(HT) Patients, Carers, Doctors, Nurses, RT s, Physicists. BCCT

3 BCCT Introduction Most common cancer in women in SA (1,121 or 27.6%/yr) Continual in last yrs 3 rd leading cause of cancer death in SA (234 or 14.7%/yr) 1989: screening mammography (50-69 yrs) 57% increase incidence of BC 82% increase in year-olds T<15 mm: 36% (2003) vs 13% (1989) 44% in yr-olds 11% reduction in MR by % in yr-olds

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5 BCCT 2011, SA Cancer Registry

6 BCCT Most common cancers in South Australia 2011 Females Incidence Mortality Site name New cases Rate Lifetime risk % all Ca Deaths Rate Lifetime Risk % all Ca Breast in in Colorectal in in Lung in in Melanoma in in NHL in in Uterus in in Leukaemia in in Pancreas in in Unknown in in Ovary in in All Cancers in in

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8 BCCT Cancer incidence + mortality rates (2011) + projections ( ), SA Females Incidence (new cases) Mortality (deaths) Site/Yr Breast (1103) (1282) (1317) (1377) (244) (301) (306) (320) CRC (589) (626) (638) (670) (190) (256) (259) (274) Mel (296) (327) (331) (344) (28) (33) (34) (36) Lung (302) (325) (334) (352) (256) (251) (257) (271) NHL (217) (191) (196) (206) (63) (85) (87) (93) All CA (4123) (4221) (4291) (4477) (1529) (1698) (1725) (1815)

9 BCCT Breast Screen 1. Younger age 2. Early stage breast cancer or DCIS 3. Improved survival 4. Increased feasibility of BCS 5. Women prefer BCS 6. QOL (cosmesis/morbidity) as IMP as cure

10 Trial No of patients F/U (mths) OS Mx (%) CS + RT (%) Milan WHO NSABP NCI-USA Denmark EORTC N/A Equivalent

11 BCCT Breast Conservation 1. Surgery Lumpectomy (60%) Wide local excision (uncommon) Segmental mastectomy (40%) Quadrantectomy (rare) 2. Radiotherapy

12 BCCT Breast Conservation Contraindications 1. Pregnancy 2. Prior radiotherapy to breast 3. Incompletely excised carcinoma 4. Extensive LVI 5. Multifocal carcinoma 6. Large tumour and relatively (predicted poor cosmesis) small breast 7. Patient declines RT 8. Pre-existing medical condition that predisposes patient to higher risk of RT side-effects (e.g. AT)

13 BCCT Aim To deliver a precisely measured RT dose to a well defined T or TV with minimal damage to NT Outcomes 1. Eradication of T 2. High QOL 3. Improved OS at a reasonable cost 4. Effective palliation if cure not possible

14 BCCT Definitions Target Volume (TV) Irradiated TV encompasses 1. Tumour or tumour bed (GTV) 2. Potential areas of local + regional microscopic ds around T (CTV) 3. A margin of surrounding normal tissue that allows for movement of the patient + target area, i.e. the breast (PTV)

15 BCCT Radiation Dose Whole Breast 50 Gy in 25# at 2 Gy/# to isocentre Gy in # at 1.8 Gy/# if large, pendulous breast Corrected for lung transmission All fields treated 5 days/week 6 MV (10 MV if large breast) photons on LA 3-D CRT or IMRT

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17 Side-effects

18 BCCT Side-effects Acute or late Local or systemic Systemic 1. Lethargy 2. Psychoemotional 3. Social

19 BCCT Side-effects Acute 1. Cutaneous (erythema, desquamation) 2. Subcutaneous 3. Oedema (a) Breast (b) Upper limb 4. Pain 5. Hair loss (axilla)

20 BCCT Cutaneous/Subcutaneous Reactions Occurs in all patients Entry and exit site Factors 1. Treatment 2. Patient 3. Tumour

21 BCCT Treatment Factors RT 1. technique 2. boost Surgery 1. extensive surgery 2. surgical complications 3. re-excision Chemotherapy 1. concomitant (uncommon)

22 BCCT Patient Factors 1. excessive skin folds (increasing patient weight: inhomogeneity) 2. large breast/obesity 3. smoking 4. pre-existing vascular disease 5. poor nutrition 6. diabetes mellitus 7. autoimmune conditions, connective tissue disease 8. genetics 9. personal hygiene, support, etc 10. (weather)

23 BCCT Tumour Factors 1. stage of cancer ( stage II tumour > x 2 the risk) 2. skin invasion 3. site (lower quadrants/boost area) 4. recurrent disease (direct effect, retreatment)

24 BCCT Pathophysiology 1. direct RT injury 2. subsequent inflammatory response Damage to 1. epithelial basal cells 2. vascular endothelial cells 3. Langerhans cells 4. sweat glands 5. hair follicles

25 BCCT Pathophysiology 1. direct RT injury 2. subsequent inflammatory response Damage to 1. epithelial basal cells 2. vascular endothelial cells 3. Langerhans cells 4. sweat glands 5. hair follicles

26 BCCT Chronic Changes Months or years 1. Hypo/hyperpigmentation 2. Hyperkeratosis, xerosis 3. Loss of hair follicles 4. Loss of sebaceous glands 5. Atrophy 6. Telangiectasia 7. Subcutaneous fibrosis 8. Ulcers 9. RT recall dermatitis

27 BCCT Management Reactions will heal Prophylactic Modern RT planning (3-D CRT, etc) + fractionation Mild (L0/I) 1. Wash with water or mild agent (moisturiser: Calendula) 2. Loose nonbinding clothing 3. Avoid talcum powder and hot/cold packs 4. Avoid irritants (perfumes, aftershave), shaving blades 5. Avoid UV light

28 BCCT Level I/IIA Bright erythema, dry desquamation 1. Cream or ointments (petrolatum-based, castor oil, balsam, trypsin, trolamine). 2. Aloe vera, d-panthenol, chamomile, slippery elm bark, sucralfate, hyaluronic acid, Vit E (not C) 3. Topical steroids esp. if pruritis (care re infection and skin atrophy;? do not prevent dermatitis)

29 BCCT Skin Care* Little evidence-based information 85% Rad Onc follow skin-care protocol 1. Evidence-based 6.5% 2. Departmental 79% 3. Anecdotal 8% Calendula, Aqueous, aloe vera, sorbolene, vitamin E Timing 1. 60% at start 2. 25% when symptomatic * M. Borg et al, NBOCC 2003

30 BCCT Skin Care Practice Question Do you allow washing with soap during radiotherapy? Do you recommend the routine application of cream or ointment? Do you provide any written instructions about skin care to your patients? Would you ever consider interrupting radiation therapy based on the severity of a skin reaction? % yes 67% 80% 88% 85%

31 BCCT Level IIB/III (moist desquamation) Avoid steroids Minimise dressing which skin dose x % When severe 1. Hydrocolloid or hydrogel (Solugel) dressings 2. Duoderm, tegaderm 3. Gentian violet 4. Pain management 5. Avoid contamination 6. Antibiotics (+/- topical) after C/S. If neutropenic? prophylactic AB to treat skin contaminants 7. Debridement in extreme cases only

32 BCCT Chronic Changes Multidisciplinary approach If skin breakdown and infection 1. Pentoxifylline (?prophylactic use also) 2. Subcutaneous interferon gamma 3. IM liposomal superoxide dismutase 4. HBO therapy

33 BCCT SUCCESSFUL TREATMENT OF RADIATION INDUCED BREAST ULCER WITH HYPERBARIC OXYGEN M Borg, D Wilkinson, V Humeniuk, J Norman. Breast, 10(4): , 2001 The radiation induced 8x4 cm ulcer persisted in spite of rigorous treatment. The ulcer completely healed following 30 hyperbaric treatments. The patient has been symptom free since completion of treatment. This report highlights the efficacy of hyperbaric oxygen therapy in the management of persisting radiation-induced ulcers.

34 BCCT Issues 1. Definition, grading (EORTC, RTOG) E.g. dry desquamation in level I 2. Very few randomised studies 3. Few studies on patients 4. Most studies published in nursing journals 5. Departmental protocols (?evidence based) 6. Under investigation GMCSF, PDGF

35 Mak et al, 2000 The effects of hydrocolloid dressing and gentian violet on radiationinduced moist desquamation wound healing. PRCT 1 trial Gentian violet significantly reduced wound size and pain (severity and frequency), and was associated with a more rapid decrease in wound size and less wound exudation. Gentian violet was associated with significantly more discomfort in dressing and aesthetic acceptance. The overall treatment time for wound healing was not statistically different between the two arms, but the time to care for the wound was significantly longer in the hydrocolloid dressing room. The study did not support the theory of moist wound healing. Gentian violet was cheaper and was associated with less frequent nursing visits and attendances to hospital. Patients could apply gentian violet on their own on a daily basis. Level II Borg et al, 2001 Successful treatment of radiation induced breast ulcer with hyperbaric oxygen Case report Reported on efficacy of hyperbaric oxygen in the management of persisting radiation induced ulcers. Level IV Graham P, Graham J, Browne L, et al, No-Sting versus Sorbolene skin care during postmastectomy irradiation PRCT Study compared the drugs in the management of confluent moist desquamation (EORTC/RTOG 3). Recommended the daily application of 3M CAVILON No Sting, which was superior to Sorbelene in the reduction of moist desquamation rates, the overall duration and degree of skin reaction as well as pruritis. There was no significant difference in pain. Level II

36 Porock et al, 1999 Management of radiation skin reactions: literature review and clinical application Review General recommendations such as the use of soft loose cotton clothing, protecting the area from the elements and the extremes of temperature, electric shaver, non-stick dressings and limiting topical agents with metal elements. The addition of salt water does not worsen the skin reaction. Preventative: Sucraflate cream was shown to reduce the severity and frequency of skin reactions. Chamomile cream also delayed the onset of the skin reaction, was preferable to patients, and reduced the incidence of moist desquamation. Mild to moderate skin reactions: No benefit to aloe vera cream. Both Aqueous cream, sorbolene and Bepanthen were superior to no cream application in the management of established skin reactions, but not for more severe reactions (moist desquamation). Moist desquamation: Application of warm saline to clean the wound followed by 1% gentian violet. One ½ strength hydrant peroxide more of an irritant. Gentian violet was not recommended because of animal data suggestive of an associated increased risk of carcinogenesis. Level III Level II Level III Level III, III and II, respecti vely Level III

37 Glean et al, 2001 Intervention for acute radiotherapy induced skin reactions in cancer patients: the development of a clinical guideline recommende d for use by the college of radiographers Overview of publications on the management of radiation induced skin reactions taken from papers published in the USA, UK and Scotland and protocols available in a number of centres in the United Kingdom, between RTOG/EORTC level 0 (no change in baseline): Regular washing and preventative use of Aqueous cream to delay onset of skin reaction. RTOG/EORTC level 1 (faint or dull erythema, dry desquamation, epilation and decreased sweating): Avoid cream build up on the skin by washing regularly. Avoid certain creams such as petroleum jelly which is poorly soluble and resides on the skin, and Lanolin base creams because of increased sensitivity. Moisturising creams significantly reduce the onset of skin breakdown (the benefit may be related to the moisturising properties of the base agent) and prevent itching thus reducing the subsequent use of steroidal cream. There is no advantage to Bepanthen or Camilasan cream. RTOG/EORTC 2A (tender or bright erythema): Use of topical steroidal cream for pruritis. Avoid prolonged use of steroidal cream as this may lead to thinning of skin and delayed healing of skin lesions, and has no beneficial effects in the presence of skin breakdown. RTOG/ERTC 2B (patchy moist desquamation, moderate oedema). The aim is to provide comfort, control pain and prevent infection. There was no advantage for antiseptics over normal saline. Dressings such as Paraffin gauze or Melonind stick to wounds increasing pain and trauma when removed. Moist wound dressings including hydrocolloid are suitable for light to medium exudating wounds, providing a moist healing environment. RTOG/EORTC 3 (confluent, moist desquamation other than skin fold; pitting oedema). Alginate sheets after saline wash convert to hydrophilic gel on contact with exudate or saline. They are also haemostatic. There is little data on the management of moist desquamation in skin folds; flexible dressing or hydrocolloid gels as used in Burns Units may be useful. Note: One study showed reported an increase in the skin dose in areas covered by dressings may increase by %, without affecting subsequent reactions. RTOG/EORTC 4 (ulceration, haemorrhage and necrosis): No data Levels II, III and IV Level III

38 CONSUMER ADVICE Radiotherapy can cause your skin to become red and inflamed during treatment. The following information aims to help you understand what skin reactions you can expect during radiotherapy and how you can limit these reactions. The nursing and radiotherapy staff at the treatment centre will talk to you about ways you can look after your skin to reduce the damage from radiation and to make yourself more comfortable. Let the radiotherapy or nursing staff know if you develop a skin reaction or if your skin reaction worsens. What could happen to my skin during radiotherapy for breast cancer? Your skin on and around the treated area could become red and dry. These skin changes look and feel like sunburn. This can begin as early as the second week of treatment, and usually improves a few weeks after stopping treatment. Patients might develop severe reactions that involve itching, peeling or blistering of the skin. Things that can make skin reactions worse There are some things that can make the skin reactions more severe. These include: 1. having chemotherapy before or at the same time as radiotherapy 2. being overweight 3. having other health problems such as diabetes 4. having sun damaged skin 5. smoking. Talk to your radiation oncologist about your risk of developing a skin reaction.

39 CONSUMER ADVICE How should I care for my skin during radiotherapy? There is evidence that the following activities can help to reduce the severity of skin reactions: wash with a mild soap or cleansing agent moisturise with a light moisturising cream ask your doctor or nursing staff about which moisturisers they recommend. You are also advised to: wear sun protective clothes or use sun screen over the treatment area when in the sun avoid irritants: it s important to protect the skin in the treatment area from damage from abrasion, chemicals (such as perfumes, deodorants, hair dyes, shaving blades) and extremes of temperature during your course of radiotherapy keep skin folds dry. What can I do to relieve symptoms? If your skin becomes red and dry, itchy or develops blisters, your treatment team can recommend creams and dressings to help reduce your symptoms and make you more comfortable.

40 CONSUMER ADVICE What should I do if my skin doesn t get better? Sometimes skin reactions get worse after the end of radiotherapy treatment. If your skin is not healed within about two weeks of completing radiotherapy treatment, contact your radiation oncologist. What can I expect after treatment? Your skin may appear darker than usual (like a suntan). This will usually fade with time. Your skin might stay dry for a few weeks after treatment finishes. The skin might also peel. To reduce dryness, continue to apply a recommended moisturising cream to the skin for a few weeks after treatment. You might have black spots. This will usually fade with time. When any symptoms have settled down you can go back to your normal skin care routine. However, it is suggested that you always protect the treated area from exposure to the sun.

41 BCCT Side-effects Late 1. Pain (breast, chest wall) 2. Fibrosis 3. Telangectasia 4. Pigmentation 5. Oedema (a) Breast (b) Upper limb (post-op): breast alone 0-4% breast + SCF 12% breast + axilla 33%

42 BCCT Side-effects Late 6. Pneumonitis and pulmonary fibrosis 7. Cardiac (a) IHD 15 yrs) (b) pericarditis (c) not ventricular dysfunction(ct) 6. Brachial plexopathy 7. Osteoradionecrosis 8. Sarcoma, other second tumours

43 CLD: central lung distance (at isocentre); MLD: maximum lung distance; L: field length Predicting pneumonitis based on CLD: 1.5 cm 6% 2.5 cm 16% 3.5 cm 26%

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46 BCCT Side-effects 1. Innovation 2. Accuracy 3. QA 4. QOL 5. Maintaining dignity

47 BCCT Solutions 1. Better patients selection 2. Alternatives to standard care 3. Improved RT techniques (IMRT) 4. Better patient care (education, nutrition, general health) 5. Better tools 6. Better anti-emetics 7. MDT

48 BCCT Tools 1. Modern digital diagnostic imaging 2. Computerised planning systems 3. Sophisticated + precise dose-delivery systems (software + hardware) 4. Daily online + virtual imaging (cone beam CT)

49 Whole Breast Phase

50 Whole Breast Phase

51 Boost Phase

52 Boost Phase

53 NEW APPROACHES

54 BCCT New Approaches Increasing Therapeutic Dose (TCP vs NTCP) SE + T coverage + Geographical misses: go hand in hand 1. 3-D CRT + IMRT 2. Deep Inspiration Breath Hold (DIBH) & Voluntary Breath Technique 3. APBI (Accelerated Partial Breast Irradiation)

55 BCCT 3-D CRT + IMRT 1. Creation of conformal dose distribution that tightly matches the TV shape in 3-D (3-D CRT) 2. Adaptation of radiation dose to TV + NT (IMRT) 3. Reduction in PTV through precise virtual knowledge of T + NT (IGRT)

56 REMOVAL OF HOT SPOTS

57 IMRT + 3-DCRT HOT SPOTS + THE HEART

58 DIBH Advantage

59 BCCT DIBH BREATHING TECHNIQUE

60 DIBH Advantage

61 APBI (Accelerated Partial Breast RT Timing Radiotherapy) Lack of consensus Increased toxicity from CT + RT LC with RT delays of >12-16/52 OS if CT is delivered after RT NBOCC recommendations: 1. Within 6/52 of surgery if no CT 2. Concomitant CT + RT (TROG trial) 3. 4/52 after taxane or anthracycline 4. Innovative approaches: APBI

62 APBI BCS (Breast Conserving Surgery) + EBRT(External Beam Radiotherapy) Advantages 1.Breast conservation 2.Cosmesis 3.Psychological

63 APBI BCS (Breast Conserving Surgery) + EBRT (External Beam Radiotherapy) Disadvantages 1.Overall treatment time (5-7/52) 2.Side-effects 3.Complexity (not square or flat) 4.Imprecise reproducibility (moves) 5.Social + economic costs

64 APBI Delivers high dose-rate RT in a short time 34 Gy in 10# in 5 days Early stage BC Low risk of disease beyond 1 site Tumour cavity cm > 90% of residual cancer 10 mm > 80% LR within same quadrant Reduced treatment time to 5 days More women will accept CS + RT

65 APBI Techniques 1. MammoSite 2. Interstitial brachytherapy (HDR) 3. Intrabeam 4. LA (IORT electrons) 5. 3-D CRT 6. IMRT Ongoing TROG study

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67 INTRABEAM TARGIT Study

68 Intrabeam Controversies 1. Histological assessment of margins not available 2. Superficial x-rays RT to seroma only 3. Unnecessary RT no MDM review 4. Small difference in LC will increase over time (LRR 1%/yr without RT) 5. Huge resource drain for little clinical gain.

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72 MammoSite Radiation source port pathway Inserted obturator to prevent bending or coiling of the catheter shaft Multilumen, silicone catheter Variable 4 to 5 cm balloon Needleless injection site

73 Ultrasound verification of catheter position Seroma fluid

74 CT planning

75 MammoSite Comparative Data Author (APBI alone) No Med F/U (m) LI (%) % ASE G3/4 % LSE G3/4 % PAIN G3/4 % Cosmesis (E-G) Explant (%) Gittleman Keisch Shah Polgar Harper Niehoff (1 RT or boost only) NR ASBS NR NR Borg (boost only)

76 APBI Key to Success 1. Proper patient selection (c. 20%) 2. Communication between BES + RO 3. Quality assurance 4. Endpoints (a) Local control (b) Cosmesis

77 APBI Side-effects 1. Pain 2. Transient erythema 3. Ecchymosis 4. Oedema 5. Local infection 6. Dry and moist desquamation 7. Mastitis 8. Symptomatic seroma

78 APBI Controversies 1. Different TV of various APBI techniques 2. Graduated inhomogeneity of single point BT sources (e.g. MSA)* 3. Optimal distance beyond PTV 4. Long-term NT SE of HDR BT 5. BED (NT + tumour) 6. Effect of CT on SE 7. LCR + OS 8. Cost of the MSA * As opposed to random hot and cold spots associated with EBRT to a mobile and irregular organ such as the breast

79 PALLIATIVE RT Introduction Essential role Maintain quality of life Relive symptoms Prevent complications Minimise side-effects Maintain dignity

80 PALLIATIVE RT Essentials Low TD 1. Lower no of higher doses/# 2. Shorter overall treatment time 3. Low risk of (tolerable) SE 4. Minimise no of attendances 5. Rapid and effective response 6. May be repeated 7. Any site and age

81 PALLIATIVE RT Local 1. Airways obstruction 2. SVCO 3. Haemoptysis Distant 1. Cerebral, PNS, choroidal 2. Bone 3. Liver 4. Cutaneous

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83 PALLIATIVE RT Spinal Cord Compression Medical Emergency 5% of patients with bone 2 Ambulation is the most important prognostic factor 1. Med S 8-9/12 if ambulatory 2. Med S 1/12 if not ambulatory T spine most common site MRI or CT-myelogram (CI to former)

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85 PALLIATIVE RT Bone Metastases RT Pain relief in 80-90% within 2/52 Frequently need re-treatment 65-85% healing/ossification of lytic lesions in unfractured bone EBRT or RN

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87 Conclusions

88 BCCT Conclusions Modern RT planning/delivery 1. Reduces geographical misses 2. Reduces local side-effects 2. Improves local control 3. Improves overall survival 4. Improves therapeutic gain

89 BCCT Conclusions Radiation therapy forms an essential part of the MD management of BC Communication between the medical team and patient + family is essential Education of the consumer + improved access to information minimise the adverse impact of BC on women and their partners