Radiotherapy and breast carcinoma

Transcription

1 Radiotherapy and breast carcinoma Krystyna Kiel, MD Radiation Oncology Rush huniversity i Mdi Medical lsh School Chicago, IL, USA

2 Role of radiation therapy in breast cancer Curative Post Post Post Mastectomy Lumpectomy Chemotherapy

3 Role of radiation therapy in breast cancer Curative Post Post Post Mastectomy Lumpectomy Chemotherapy ADVANCED BREAST CANCERS

4 Radiotherapy concepts Local treatment (like surgery) Probability of control by radiotherapy is related to Volume of cancer Radiotherapy dose The target has to be well defined

5 Radiotherapy concepts Local treatment Probability of control by radiotherapy is related to Volume of cancer Radiotherapy dose The target has to be well defined

6 Nodal coverage with standard breast radiation fields (Loyola)

7 Nodal radiation Usually requires an additional matched field

8 Radiotherapy concepts Local treatment (like surgery) Probability of control by radiotherapy is related to Volume of cancer Radiotherapy dose The target has to be well defined

9 Radiotherapy concepts Local treatment (like surgery) Probability of complications by radiotherapy is related to Normal tissue in fields Radiotherapy dose The target has to be well defined

10 CONTROL BY RADIATION THERAPY

11

12

13 BENEFITS VS RISKS

14 Complicationsof of breast radiotherapy Complication Incidence Treatment Factor Lymphedema 14-54% Axillary dose Surgery Brachial plexopathy 0.4-5% Axillary dose Pneumonitis 1-9% Lung volume Chemotherapy Rib fractures 1-5% RT dose Chemotherapy Cardiac % Cardiac volume Chemotherapy Carcinogenesis i 0102% % Vl Volume Dose

15 Radiotherapy concepts Local treatment (like surgery) Probability of control by radiotherapy is related to Volume of cancer Radiotherapy dose The target has to be well defined

16 Breast or chest wall volumes Breast irradiation at Partial breast radiation studies suggest that the entire breast need not be treated Avoiding lung and heart probably more important that treating the extreme edges of the breast (unless the tumor is located there) Marked the surgical cavity is very helpful The entire mastectomy site should be treated. The scar should be included Drain sites are generally included.

17 Defining breast volume Very difficult to define the breast clinically or on a CT scan Palpable breast tissue does not always correlate with visualized tissue Experience has shown us tumors can occur out of the usual boundaries I Nth l d t d th iti i l t 4 In a Netherlands study, the variation in volume amongst 4 radiation oncologists was 17.5%, ranging from 11 to 27%.

18 1. Breast conservation therapy 2. Postmastectomy radiation therapy Other issues: How should radiotherapy be integrated with neoadjuvant therapy? What is the best radiotherapy schedule? Does one need advanced technology?

19 Radiation therapy after breast conserving surgery Early Breast Cancer Trialists Collaborative Group (Lancet 2005;366: ) (ASCO 2007Educational Book, p3 6)

20 Why is local control important? Early Breast Cancer Trialists Collaborative Group Radiation reduces the risk of recurrence by ~75% Impact of mortality seen late (~15 years) Local recurrence leads to a 15 year breast cancer mortality ratio by 41 4:1 <10% reduction in LF translates into 1% survival benefit 10 20% reduction in LF translates into 4.5% survival benefit >20% reduction in LF translates into 6% survival benefit

21 Oxford overview of postmastectomy radiation therapy 72 % reduction of local recurrence 5% improvement tin breast cancer free survival Lancet 366:2087, 2005

22 POSTMASTECTOMY RADIATION THERAPY 1. Rationale 2. Target 3. Technique

23 Rationale 1. Some breast cancers ce will recur on the chest wall or in regional nodes after mastectomy. 2. Not all recurrences are salvageable. 3. Preventing these recurrences will improve quality of life and survival.

24 Why worry about recurrences? Vancouver Trial 90% of pts with local recurrences died by 10 years

25 Risk factors for local recurrence after mastectomy Positive nodes Large tumors Skin involvement Lymphovascular invasion Poor response to neoadjuvant chemotherapy

26 Locoregional recurrence after mastectomy & adriamycin based chemotherapy (MDAH) 10 yr actuarial rate of isolated LRF by tumor size and nodal status T stage No LNs 1-3 LNs 4-9 LNs 10+ LNs T1 6% 7% 9% 17% T2 T3 11% 29% 12% 29% 23% 31% 17% 29%

27

28

29 LOCALLY ADVANCEDORNEGLECTED LOCALLY ADVANCED OR NEGLECTED BREAST CANCER

30 MDAH study of postmastectomy RT in patients treated with neoadjuvant adriamycin based chemotherapy 10 year locoregional failure rates 713 pts treated by mastectomy 136 pts No XRT 579 pts XRT 22% 12% (Huang JCO 2005)

31 10 yr Locoregional Recurrence Rate pcr in breast LN or LN+ Residual disease LN Residual disease LN+ 0% 10.5% 20.3%

32 Cause specific survival in subset analysis

33 Do patients with a path CR need postmastectomy RT? Recurrences in clinical Stage II disease Recurrence free survival in clinical Stage III disease No RT 0/20 RT 0/10 MDAH McGuire, IJROBP

34 Preoperative chemotherapy and radiation therapy for locally advanced breast cancer Could one substitute radiation therapy for surgery? Dusseldorf study 315 pts, 192 sequential, 113 concomitant 50 Gy in 25 fractions and10 Gy interstitial or electron boost Roth, 2008

35 Locally advanced breast cancer Is Breast conserving treatment possible after preoperative chemotherapy? Bonadonna et al 62% PR in tumors >5 cm, & 93% with tumors 3 5 cm 73% with tumors >5 cm candidates for BCT Mauriac et al 63% of preop pts had BCT, with better survival NSABP 37% CR and 80% response to AC x 4 65% of preop chemo underwent BCT

36 Does more chemotherapy improve outcome?

37 Is 6 weeks of radiation therapy necessary? ALTERED FRACTIONATION SCHEMES

38 START TRIAL results 40% Local failure 30% Change in breast appearance 20% 10% 0% 40/3wk qd 50/5wk qd 39/5 wk qod 41.6/5 wk qod Dose (Gy)/# wks Local failures <5%

39 Ontario Clinical Oncology Group Study: 10 year followup (Whelan, NEJM 2010) 1234 patients randomized to 50 Gy in 5 wks versus 42.5 Gy in 3 wks

40 Hypofractionation studies in breast cancer Author Year Stage Follow up RT schedule # pts Local failures START A 2008 T1 3a British iih N0 1 START B British 2008 T1 31 N0 1 Grade 3 Toxicity 6 yr 40 Gy/15 fx/3 wks % 5 yr % 6 YR 41.6 Gy/13 fx/5 wks % 5 yr % START B 2008 T YR 39 Gy/13 fx/5 wks % % British N0 1 Kirova Paris 2009 T 2 N mos 32.5 Gy/5 fx/1x per wk 50 9% 7 yr 2% Wu 2003 Postop 45 Gy/15 fx/5 wks % Beijing Wu Beijing 2003 Postop 23 Gy/4 fx/17 days % Koukourakis 2001 T Gy/12 fx/3 wks 15 CR 73% 7% Greece Pinnaro, Rome Whelan, Canada 2010 Tis T2 N Tis T2 N0 43 mos median 34 Gy/10 fractions/2 wks + boost 8 Gy/1 12 yr 42.5 Gy/16 fractions/3 wks 39 0% 0% % 10 yr 4%

41 TECHNOLOGY

42

43 6 MV Cobalt 60 Right Breast (separation <17 cm) PTV Min dose 97% 95% Max dose 105% 106% Median dose 100% 100% Lung Volume >20 Gy 2.2% 3.4% Cost Equal Initial Costs Source Technical Higher Lower support Comparison of cobalt vs 6 MV beams Adams, Royal Marsden, 2008

44

45 Beam energy Beam energy 4 6 MV photons preferred > cm separation, 8 10 MV photons suggested But JCRT found no difference in local control But, JCRT found no difference in local control or complications by treatment energy!

46 Other important issues in treating breast cancer Radiation therapy technique

47 IMPORTANCE OF TECHNIQUE 36 trials comparing Absolute improvement postmastectomy RT to none in survival Trials delivering Gy Trials il delivering dli i inadequate dose Trials with inappropriate target 2.9% 5-year 6.4% 10-year None None (Gebski et al, JNCI, Jan 2006)

48 Positioning Reproducible Generally supine Use of breast board Adjustable angle to reduce chest wall slope and increase patient comfort Molds or Vacu lok Support for abducted arm Immobilization of large breasts

49 Technique and complications Lung volume vs central lung distance Central lung distance % ipsilateral lung 1.5 cm 6% 2.5 cm 16% 35cm %

50 TREATMENT PLANNING

51 Simulation 1. Establish borders of breast and borders of tangential fields 2. Determine angle of tangential fields 3. Measure separation 4. Assess amount of lung and heart in radiation fields 5. Contour the breast or chest wall 6. Make sure that target volume is in the field with adequate margin for dose buildup (especially extreme medial and lateral tumors)

52 Advantages of CT planning Target definition and at risk volumes more easily done Accurate and multiple contours of the breast. 3 dimensional treatment plans Lung inhomogeneity However, One can manually contour the breast or chest wall outside the central cut No data that suggests that the results of treatment are improved with these techniques

53 Picking theprescription point 1 cm from isocenter 1.5 cm from isocenter 2.0 cm from isocenter 1/3 rd the distance to skin ½ the distance to the skin

54 Compensation & Physics Planning

55 Central cut vs entire breast 20-30% hot spots seen in other portions of the breast Compensation or Compensation or degree of wedging can change

56 Node coverage

57 Covering nodes with standard breast radiation fields To cover axilla in 90% of cases Extend field to humeral head Make sure 1 cm lung is seen in the area

58 Risk of regional failure with & without radiation in patients with ih4 or more positive ii nodes No regional RT Regional RT All patients 11% 2% Axillary node fil failure 5% 0% Supraclavicular 11% 2% node failure Grills, Beaumont Hosp, IRJOBP 2003

59

60 Radiotherapy for Breast Cancer in Countries with Limited Resources: Program Implementation and Evidence Based Recommendations Nuran Senel Bese, MD,* Krystyna y Kiel, MD, Brahim El Khalil El Gueddari, MD, Oladapo Babatunde Campbell, MD, Baffour Awuah, MD, and Bhadrasain Vikram,MD,#for the International Atomic Energy Agency Stage Ior II breast cancer Whole breast RT All 50 Gy/25/5 wks or 42.5 Gy/16/4 wks, 5X per wk Pts <age 50 or close margins additional 16 Gy boost Postmastectomy RT (+) axillary nodes 50 Gy/25/5 wks to chest wall & supraclavicular LNs; include axilla if inadequate dissection ( ) axillary nodes & multiple adverse features (T2, LVI, or positive margins) 50 Gy/25/5 wks to chest wall Locally advanced breast cancer After neoadjuvant therapy and lumpectomy: whole breast RT After neoadjuvant therapy and mastectomy: postmastectomy RT Persistent unresectability after chemotherapy, preoperative RT to breast and nodes Persistent unresectability after chemotherapy and RT, high dose RT Metastatic or recurrent breast cancer Single symptomatic bone mets 8 Gy/1 Multiple symptomatic bone mets: wide field or hemibody RT 12 Gy/4/2 days or if prepped 6 8 Gy/1 fraction Symptomatic brain mets 30 Gy/10 or 20 Gy/5; craniotomy or radiosurgery to selected patients Symptomatic soft tissue mets rapid fractionation Locally recurrent breast cancer: postmastectomy RT with high dose boost to gross disease