Contouring in breast cancer current practice and future directions

It explains RTOG and EORTC breast contouring in detail and what revisions should me made to present guidelines

1. Contouring in Breast Cancer Current Practice and Future Directions Dr Anil Gupta AIIMS, New Delhi

2. INDEX Need of RT Post BCS and Post Mastectomy Need of Contouring guidelines Various Contouring guidelines RTOG Contouring EORTC Contouring Controversies

3. Impact of RT after BCS EBCTCG meta analysis 2011 Breast Conservative Treatment = BCS + LR RT

4. Impact of Post Mastectomy RT + RNI EBCTCG meta analysis 2005 Radiotherapy produces its greatest absolute effects on local recurrence in women who are at greatest risk of local recurrence. For, whether the underlying risk is low or high, about 70% of it can be avoided by radiotherapy No OS benefit

5. Impact of Post Mastectomy RT + RNI EBCTCG meta analysis 2014 Addressed treatment of node 1-3 issue

6. Indications of PMRT Tumor > 5 cm (>T3) Node Positive Positive margins

7. Need of Contouring guidelines RT has undergone transition from 2 D to 3 D Planning Newer techniques- Better Conformality/ Lower toxicity However, accurate identification of Clinical Target Volume becomes necessary

8. RTOG- expert consensus guidelines ESTRO- expert consensus guidelines RADCOMP- RTOG 3509/3510 studies- randomized trial of proton therapy versus photon therapy for breast cancer TROG 12.02 PET LABRADOR

9. CLINICAL ANATOMY

10. Deep relations of the breast Lies on deep fascia/pectoral fascia covering the pectoralis major. Is separated from pectoral fascia by loose areolar tissue- retromammary space. Clinical importance ;- if retromammary space infiltrated. Fixity of breast

11. CT Anatomy Pectoralis Major Pectoralis Minor Subscapularis Axillary Vein

12. Glandular tissue of breast Lattismus Dorsi m Sternum Scapula Serratus anterior Intercostal m

13. RTOG- Overlying Principles Before Planning CT- Clinical breast/ Clinical Chest wall should be marked by radiopaque markers Includes the apparent CT glandular breast Incorporates consensus definitions of anatomical borders Includes lumpectomy CTV Includes the mastectomy scar (may not be feasible for occasional cases where scar extends beyond the typical borders of chest wall)

14. Cranial Clinical Reference + Second rib insertion Caudal Clinical reference + loss of CT apparent breast 12/15/2019

15. Posterior : Breast - Excludes pectoralis muscles, chestwall muscles, ribs Breast + Chestwall ( Stg >IIIA )- Includes pectoralis muscles, chestwall muscles, ribs Chestwall - Rib-pleural interface. (Includes pectoralis muscles, chestwall muscles, ribs) Anterior: Skin

16. Medial Sternal rib junction Lateral Clinical Reference + mid axillary line typically, excludes latissimus (Lat.) dorsi m . 12/15/2019

17. Cranial Residual breast-Upper border of palpable/ visible breast tissue; maximally up to the inferior edge of the sternoclavicular joint Thoracic wall-Guided by palpable/visible signs; if appropriate guided by the contralateral breast; maximally up to the inferior edge of the sterno -clavicular joint Caudal Residual breast-Most caudal CT slice with visible breast Thoracic wall-Guided by palpable/visible signs; if appropriate guided by the contralateral breast ESTRO- Vessel based Contouring

18. Posterior : the skin and subcutaneous tissue to the anterior surface of pectoralis major, and only recommends inclusion of the pectoralis muscles and ribs in the setting of documented invasion for T4a and T4c tumors (In contrast to RTOG which covers pectoralis major and rib in all cases) Anterior: 5 mm under skin surface

19. Medial Lateral to the medial perforating mammarian vessels; maximally to the edge of the sternal bone Guided by palpable/visible signs; if appropriate guided by the contralateral breast Lateral Lateral breast fold; anterior to the lateral thoracic artery Guided by palpable/visible signs; if appropriate guided by the contralateral breast. Usually anterior to the mid-axillary line

20. Challengers

21. 5 surgical case series with 278 patients with chest wall recurrence Deep Chest wall recurrences = 0

22. Multi Institutional study of mapping local and regional recurrences in patients treated between 2006 and 2014 Only included patients with recurrences, No information on total number and proportion of recurrences Patients treated with conventional field borders, with tangents, SCF and ICF Level III and IMC Mapped these recurrences on contoured volumes of ESTRO and RTOG The incidence and location of LRRs ‘‘outside ESTRO-, inside RTOG-CTVs”, and ‘‘outside RTOG-CTV noted

23. Inside ESTRO CTV Inside RTOG outside ESTRO CTV Outside RTOG CTV Local recurrences Regional recurrence in the axillary & IMN Regional recurrence in the supraclavicular/infraclavicular nodal area

24. In BCC 96% LRR was inside ESTRO The rate of LR located outside the ESTRO-CTV but inside the RTOG-CTV was 28.9% for mastectomy patients Sizable risks of geographic target misses were found in mastectomy patients with a thin chest wall and in patients with certain indicators of aggressive tumor behaviour, including young age and triple negative tumors , as well as advanced stage Recurrence rate outside the ESTRO and RTOG-CTVs of the LN supraclavicular was high (30%) and concentrated in the posterior lateral side of the SCL fossa, more so in young age and TNBC

25. OAR toxicities

26. Isolated recurrences deep to the pectoralis are uncommon,and routine inclusion of the ribs and intercostal muscles in the chest wall CTV might not be necessary for routine applications of postmastectomy radiation therapy Inclusion of the ribs and intercostal muscles in the chest wall CTV as recommended by the RTOG contouring guidelines significantly increase the doses to the heart and lungs

27. Lumpectomy GTV Include seroma cavity Include all surgical clips when present Use pre-operative imaging Pre-operative and per-operative clinical findings Architectural changes in planning CT 12/15/2019

28. Identifying seroma cavity in open cavity surgery Landis et al 2007

29. Identifying seroma cavity in closed cavity surgery

30. Identifying seroma cavity in closed cavity surgery 12/15/2019 33 AIIMS ACADEMICS 2018

31. 12/15/2019 34 AIIMS ACADEMICS 2018

32. Define delineation guidelines for the clinical target volume (CTV) for PMRT in the immediate breast reconstruction (IBR) implant/prosthesis based (IBR- i )and autologous IBR (IBR-a)

33. (A) retropectoral with full coverage by the pectoral muscle; (B) retro-pectoral with partial coverage by the pectoral muscle and supportive material in the lower part; (C) pre-pectoral with full coverage by supportive material Implant positioning

34. Retropectoral - If the dorsal fascia of the breast is not involved by cancer- CTV ventral Pectoralis Major Implant only subcutaneous lymphatic plexus to be covered

35. Retropectoral with partial coverage or rectropectoral with dorsal fascia involvement by cancer CTV ventral CTV dorsal Pectoralis Major Implant lymphatic plexus should be irradiated as well as the part of the chest wall that was initially not covered by the pectoral muscles

36. Pre-pectoral implant CTV ventral CTV dorsal Pectoralis Major Implant

37. Regional Nodes AXILLA SCF IMN

38. RT to Supraclavicular Region alone 1-2 Node +ve in SLNB with no dissection Post BCS or MRM with 1-3 nodes positive Clinical N2 OR N3 disease

39. Indications of RT to Axilla + SCF Axilla N+ with extensive ECE SN+ with no dissection (1-2 SLNB positive may be avoided) Inadequate axillary dissection High risk with no dissection Post BCS or MRM with ≥4 nodes positive

40. Internal Mammary Node Irradiation Individualized Consider for Central and medial lesions with high risk +SLN IN IMN chain +SLN in axilla with drainage to IMN on scintigraphy Stage III breast cancer Positive Axillary nodes

41. Level I- lymph nodes lateral to lateral border of pectoralis minor Level II- lymph nodes between medial and lateral borders of pectoralis minor and interpectoral lymph nodes. Lymph III- nodes medial to medial margin of pectoralis minor Axillary Lymph Nodes (Surgical Anatomy)

42. Other groups of lymph nodes Internal mammary lymph nodes- in the intercostal spaces along the edge of the sternum. Supraclavicular lymph nodes- in the supraclavicular fossa Intramammary lymph nodes- within the breast are considered as axillary LNs for staging.

43. 12/15/2019 Axillary Vessels

44. 12/15/2019 47 AIIMS ACADEMICS 2018 Deltoid M

45. RTOG- Nodal Contouring Supraclavicular Cranial - Caudal to the cricoid cartilage Caudal - Junction of brachioceph .- axillary vns ./ caudal edge clavicle head Anterior - Sternocleido mastoid (SCM) muscle Posterior- Anterior aspect of the scalene m. Lateral - Cranial: lateral edge of SCM m. Caudal: junction 1st rib-clavicle Medial - Excludes thyroid and trachea

46. Axilla Level I Cranial- Axillary vessels cross lateral edge of Pec . Minor m. Caudal- Pectoralis ( Pec .) major muscle insert into ribs Anterior- Plane defined by: anterior surface of Pec. Maj. m. and Lat. Dorsi m Posterior- Anterior surface of sub scapularis m . Lateral- Medial border of lat. dorsi m. Medial- Lateral border of Pec . minor m

47. Axilla level II Cranial- Axillary vessels cross medial edge of Pec . Minor m. Caudal- Axillary vessels cross lateral edge of Pec . Minor m Anterior- Anterior surface Pec . Minor m. Posterior- Ribs and intercostal muscles Lateral- Lateral border of Pec . Minor m. Medial- Medial border of Pec . Minor m.

48. Axilla level III Cranial- Pec . Minor m. insert on cricoid Caudal- Axillary vessels cross medial edge of Pec . Minor m Anterior- Posterior surface Pec . Major m Posterior- Ribs and intercostal muscles Lateral- Medial border of Pec . Minor m. Medial- Thoracic inlet

49. Internal mammary nodes Encompass the internal mammary/ thoracic vessels Cranial- Superior aspect of the medial 1st rib Caudal- Cranial aspect of the 4th rib

50. EORTC- Vessel Based Contouring Lymph node level 4 (same as Supraclavicular) Cranial - Includes the cranial extent of the subclavian artery (i.e. 5 mm cranial of subclavian vein) Caudal- Includes the subclavian vein with 5 mm margin, thus connecting to the cranial border of CTVn_IMN Anterior- Sternocleidomastoid muscle, dorsal edge of the clavicle pleura Posterior- Including the jugular vein without margin; excluding the thyroid gland and the common carotid artery Lateral- Cranial: lateral edge of SCM m. Caudal: junction 1st rib-clavicle Medial- Includes the anterior scalene muscles and connects to the medial border of CTVn_L3

51. Axilla Level I Cranial- Medial: 5 mm cranial to the axillary vein Lateral: max up to 1 cm below the edge of the humeral head, 5 mm around the axillary vein Caudal- To the level of rib 4 – 5, taking also into account the visible effects of the sentinel lymph node biopsy Anterior- Pectoralis major & minor muscles Posterior- Cranially up to the thoraco -dorsal vessels, and more caudally up to an imaginary line between the anterior edge of the latissimus dorsi muscle and the intercostal muscle. Lateral- Cranially up to an imaginary line between the major pectoral and deltoid muscles Medial-

52. Axilla level II Cranial- Includes the cranial extent of the axillary artery (i.e. 5 mm cranial of axillary vein). Caudal- The caudal border of the minor pectoral muscle Anterior- Anterior surface Pec . Minor m. Posterior- Ribs and intercostal muscles Lateral- Lateral edge of minor pectoral muscle Medial- Medial edge of minor pectoral muscle

53. Axilla level III Cranial- Includes the cranial extent of the subclavian artery (i.e. 5 mm cranial of subclavian vein ) Caudal- 5 mm caudal to the subclavian vein. If appropriate: top of surgical ALND Anterior- Major pectoral muscle Posterior- Up to 5 mm dorsal of subclavian vein or to costae and intercostal muscles Lateral- Medial side of the minor pectoral muscle Medial- Junction of subclavian and internal jugular veins – >level 4

54. Internal mammary node Caudal limit of CTVn_L4 Cranial side of the 4th rib

55. Nodal Recurrence Mapping

56. The primary goal was to map the anatomic pattern of isolated nodal recurrences (NR) in the supraclavicular (SCV), axillary, and internal mammary nodes (IMNs) in patients with breast cancer treated with curative-intent surgery with or without radiation therapy (RT)

57. Patients with NR after treatment at a single cancer center during 1998 to 2013 were identified All NRs were overlaid onto representative axial computed tomographic images The locations of 243 NRs among 153 eligible patients were mapped

58. Results NRs were confirmed by pathology in 73% The majority of NR occurred in the axilla (42%; 102/243) IMN (32.5%; 79/ 243) SCV (25.5%; 62/243) Radiation Therapy Oncology Group (RTOG) or European Society for Radiation therapy and Oncology (ESTRO) clinical target volume encompassed 82% (198/243) of NRs The majority of out-of-field NRs were located in the lateral and posterior SCV region for both RTOG (67%; 30/45) and ESTRO (89%; 49/55) guidelines.

59. Specifically, the RTOG-CTV group included 82% (198/234) and the ESTRO-CTV group included 77% (188/234) of the NRs The SCV group harbored the bulk of out-of-field recurrences from both RTOG (missing 48% or 30/62 of SCV recurrences) and ESTRO (missing 79% or 49/ 62 of SCV recurrences) guidelines, followed by the IMN (2.5%; 2/79 for both) and axilla (13% or 13/102 for RTOG, and 1% for ESTRO)

60. To investigate incidence and location of locoregional recurrence (LRR) in patients who have received postoperative locoregional radiotherapy (LRRT) for primary breast cancer Medical records were reviewed for all patients who received postoperative LRRT for primary BC in southwestern Sweden from 2004-2008 (N=923) Patients with LRR as a first event were identified (N=57)

61. Conclusions Deep Chest wall recurrences are uncommon and routine inclusion of it in target volume leads to higher lung and cardiac toxicities There is geographical miss in posterior and lateral supraclavicular region These evidences should be addressed in expert based consensus guidelines