Percorso di cura e trattamento riabilitativo della paziente operata di tumore alla mammella

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1 Percorso di cura e trattamento riabilitativo della paziente operata di tumore alla mammella La chirurgia oncoplastica della mammella Il moderno approccio alla chirurgia ascellare Venere e Cupido, Moreelse Paulus, 1617, Hermitage - St.Petersburg Dott. PC Rassu, 2013

2 1 Oncoplastic Breast Surgery Così come si provocano o si esagerano i dolori dando loro importanza, nello stesso modo questi scompaiono quando se ne distoglie l'attenzione. Sigmund Freud Dott. PC Rassu, 2013

3 1894 massimo trattamento tollerabile

4 TRIAL MILANO I (1981) (T1 N0 : QUART VS HALSTED) 1981 minimo trattamento efficace

5 In pratica Dott. PC Rassu, 2013

6 = 87 anni Mastectomia radicale di Halsted, mastectomie modificate sec. Patey e Madden con linfadenectomia ascellare = 24 anni Quadrantectomia + radioterapia + linfadenectomia Quadrantectomia + radioterapia + biopsia linf sentinella 1998 oggi Chirurgia Oncoplastica + radioterapia + biopsia linfonodo sentinella Dott. PC Rassu, 2013

7 Definizione di Chirurgia Oncoplastica Consensus Conference Firenze 1998 Il termine di chirurgia oncoplastica comprende in sé il doppio significato di resezione oncologica, finalizzata al controllo locale della malattia, e di ricostruzione plastica per ottenere il migliore risultato cosmetico possibile. Dott. PC Rassu, 2013

8 Il chirurgo senologo oncoplastico Punti chiave Criticità Volume tumore/volume mammella Curva di apprendimento (tecnica e culturale) Forma della mammella Localizzazione del tumore Caratteristiche del tumore Terapie adiuvanti (RT, CT, HORMT) Complicanze postoperatorie (liponecrosi 5%) Tempo di sala operatoria (maggiori risorse) Corretta informazione alla paziente Desideri della paziente Gruppo di Specialisti Dott. PC Rassu, 2013

9 Interventi chirurgici personalizzati Casi clinici personali Dott. PC Rassu, 2013

10 Chirurgia oncoplastica della mammella Removing a portion higher than 20% of the whole breast volume is a predictive factor of poor aesthetic outcome European Breast Cancer Conference (Vienna 2012): Oncoplastic Techniques VOLUME DISPLACEMENT 1st level: reshaping with glandular flaps with/without contralateral carried out by oncoplastic breast surgeon 2nd level: glandular reshaping by means of upper, mid, lower and lateral peduncle flaps, performed by the oncoplastic breast surgeon and without the support of the plastic surgeon 3rd level: conservative mastectomies (nipple sparing, skin sparing, skin reducing) and reconstruction with expandable implants, performed jointly by the breast and plastic surgeons VOLUME REPLACEMENT 4th level: complex mammary reconstruction with muscle and skin flaps that require the exclusive presence of the plastic surgeon

11 Margini > 3 cm 16% 2 cm 40% 1 cm 57%

12 For successful results surgeons and patients should discuss their options before surgery and the surgeon should ideally be proficient in various oncoplastic techniques The surgical margin status has been accepted to be the most important risk factor, because it is the only risk factor which is controllable by surgeon. surgeon There is no clear consensus as to the definition of a positive surgical margin. margin It might be reasonable for positive surgical margins to include atypical cells, in situ or invasive cancer cells within 5 mm from cut surface Oncoplastic surgery, such as the use of a partial flap and the insertion of a prosthesis, could be an option for obtaining both a clear resection margin and a better cosmetic result

13 What is a negative margin? for Radiation Oncologists in North America No malignant cells seen on the inked surface No malignant cells seen at: 1 mm 2 mm 3 mm 5 mm 10 mm for Radiation Oncologists in Europe 15% 21% 50% 12% 10% 3% No malignant cells seen at > 5 mm Meta-analysis by Wang et al. > 10 mm Meta-analysis by Houssami et al. No statistical difference in local recurrence associated with margin widths of more than 1 mm, more than 2 mm, or more than 5mm after adjustment for a radiation boost and endocrine therapy

14 Recidiva locale dopo chirurgia oncoplastica

15 Fattori di rischio della recidiva locale Grado 3 RR 2,5 Ca lobulare invasivo RR 2,5 Margini positivi RR 2,4 Invasione linfovascolare RR 1,8 pt > 2cm RR 1,5 Linfonodi positivi RR 1,4 Età < 40 anni RR 1,4 Canada, NSABP B-06, Milano 2 e 3 Trials

16 Preoperative breast MRI imaging Preoperative breast MRI changed the surgical plan to more extensive surgery in 34% of cases. tumor positive resection margins control group 15.8% 29.3% (p < 0.01) Impact on surgical management attributed to MRI findings conversion to mastectomy conversion to wider excision conversion from wide local excision to mastectomy 8.3% 4.5% 8.1%

17 Lancet 2005 La recidiva locale assume un significato prognostico Confermato anche nella revisione del 2011

18 Neoplasia del quadrante supero esterno Reshaping ghiandolare di 1 livello con centralizzazione del NAC Dott. PC Rassu, 2013

19 Neoplasia del quadrante supero esterno Reshaping ghiandolare di 1 livello Dott. PC Rassu, 2013

20 Neoplasia della confluenza dei quadranti inferiori Reshaping ghiandolare di 2 livello: lembo a peduncolo superiore Dott. PC Rassu, 2013

21 Neoplasia della confluenza dei quadranti superiori Reshaping ghiandolare di 2 livello: lembo a peduncolo inferiore Dott. PC Rassu, 2013

22 Le mastectomie conservative sec. Nava Chirurgia Oncoplastica di 3 livello SKIN REDUCING MASTECTOMY SEC.NAVA Dott. PC Rassu, 2013

23 Le mastectomie conservative sec. Nava Chirurgia Oncoplastica di 3 livello SKIN SPARING MASTECTOMY Dott. PC Rassu, 2013

24 Le mastectomie conservative sec. Nava Chirurgia Oncoplastica di 3 livello NIPPLE SPARING MASTECTOMY Dott. PC Rassu, 2013

25 Oncoplastica Impiego della cellulosa ossidata rigenerata Indicazioni - Filler in qualunque settore ghiandolare - Parenchima mammario con scarso contenuto adiposo - Mammella piccola Dott. PC Rassu, 2013

26 Dott. PC Rassu, 2013

27 Il confort della paziente: la gestione della ferita chirurgica e il miglior risultato cosmetico possibile Dal 13 al 35% dei pazienti medicati con cerotti convenzionali sviluppano delle vescicole dolorose capaci di ritardare la guarigione della ferita e aumentare il rischio di infezioni del sito chirurgico Ousey K. et al. Understanding and preventing wound blistering. Wound UK, Dott. PC Rassu, 2013

28 Mepilex Border Post-Op

29 Dott. PC Rassu, 2013

30 2 Il Development of axillary surgery in breast cancer tocco supremo dell'artista: sapere quando fermarsi ARTHUR CONAN DOYLE "L'avventura del costruttore di Norwood Dott. PC Rassu, 2013

31 Razionale storico della dissezione ascellare 1. Migliore controllo locale della malattia 2. Prevenzione delle recidive ascellari 3. Miglioramento della sopravvivenza nei casi di macrometastasi 4. Completamento della stadiazione con indicazione alla chemio/radioterapia *

32 Timeline of the axillary surgery Axillary Dissection 18th century Heister: axillary dissection as part of the treatment of invasive breast cancer 1875 Volkman observed the communicati on of the mammary lymphatic vessels with the axillary nodes 1867 Moore proposed the complete removal of the breast and the diseased glands 1882 Banks and Moore: the axillary nodes should be removed even when they were not clinically involved 1891 William Halsted described the theory of centrifugal spread of breast cancer SNB 1948 Patey and Dyson less radical approach: the pectoralis major was preserved Veronesi National Krag, QUA-Rt Cancer SNB for achieved the Institute breast same results Bethesda cancer of radical mastectomy + ALND as integral Morton DL, Wen DR, Wong JH et al part of the (1992) Technical details of procedure intraoperative lymphatic mapping for early stage melanoma. Arch Surg 127:

33 Linfonodo sentinella Accuratezza diagnostica 96.5% - Valore predittivo negativo 94-96% - Falsi negativi ~ 5% La probabilità di trovare un sentinella positivo nelle pazienti clinicamente negative è del 20-30% LINFONODO SENTINELLA POSITIVO PER CELLULE TUMORALI ISOLATE (cluster di cellule con Ø massimo < 0,2 mm) mm LINFONODO SENTINELLA POSITIVO PER MICROMETASTASI (0,2 mm < Ø < 2 mm) mm screening LINFONODO SENTINELLA POSITIVO PER MACROMETASTASI (Ø > 2 mm) mm

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35 Dutch MIRROR retrospective study (chemo, hormonal,both) Disease Free Survival A pn0-85.7% B pn0[i+] / pn1mi % < C pn0[i+] / pn1mi % < year Adiuvant therapy p Isolated tumor cells or micrometastases in regional lymph nodes were associated with a reduced 5-year rate of disease-free survival among women with favorable early-stage breast cancer who did not receive adjuvant therapy. In patients with isolated tumor cells or micrometastases who received adjuvant therapy, disease-free survival was improved

36 the incidence of nonsentinel node metastases increased as the primary tumor increased in size and more important the size of sentinel node metastases. T1 lesions (< 2 cm) nonsn MTS SN micromts 6% (0,2 2 mm) SN macromts 47,5% ( > 2 mm)

37 Axillary Dissection is still usefull? Yes.. Axillary lymph node dissection (ALND) has remained standard treatment for women with node-positive disease detected clinically and/or confirmed pathologically, irrespective of the primary tumour characteristics. Removal of axillary nodes containing tumour foci provides regional control and may remove a potential source of distant metastases but Even after ALND of level I and II, up to 30% of positive lymph nodes remain in the axilla but Extended surgery is considered to be less influential on overall survival in patients with breast cancer than systemic therapy and radiotherapy

38 in fact with adjuvant therapy and radiotherapy

39 How to study axillary lymph nodes? actual indications Guidelines and Clinical Recommendations Dott. PC Rassu, 2013

40 Axillary staging Surgical Staging Sentinel Lymph Node Biopsy Axillary Lymph Node Dissection Instrumental + Surgical Staging Instrumental Staging Clinical examination US + FNAC/CB Digital Mammography Computed Tomographyc Scan Positron Emission Tomography Magnetic Resonance Imaging

41 Physical examination Clinical examination is the oldest and most rudimentary method used to evaluate lymph node status and manifestly inaccurate for axillary staging: the physician cannot differentiate between an enlarged lymph node that is cancerous versus one that is inflamed or reactive. Among patients with non-palpable nodes in the axilla, the histopathological presence of metastasis was found in 35 40% Lanng showed in a study involving 301 patients that even if the examination was performed by a specialist breast surgeon, the examination had little value. When the surgeons considered the axilla to be normal, they were wrong in 44% of cases. cases sensitivity: 25 32%

42 US examination Metastases develop preferentially in the LN cortex sensitivity: 45 86% Rounded shape, a long-to-short axis ratio of 2, hypoechoic, compression or disappearance of the fatty hilum, cortical thickening or asymmetry If a suspicious lymph node is found on imaging, patients may undergo US-guided fineneedle aspiration or core needle biopsy to obtain a cytologic or histologic diagnosis

43 MR examination sensitivity: 37% lesions 2 mm may not be visualized directly

44 FDG-PET examination FDG-PET is not yet sufficiently sensitive in the detection of lymph node metastases; the modest results of PET in the detection of micrometastases are likely due to the limited spatial resolution of the current PET scanners Spatial resolution of PET scanner: -adequate (sensitivity 100%) for metastases 10 mm in diameter -acceptable (sensitivity 83%) for metastases between 6 and 9 mm -inadequate (sensitivity 23%) for metastases <5 mm sensitivity: %

45 La biopsia del linfonodo sentinella è da considerare lo standard per le pazienti con linfonodi ascellari clinicamente negativi o con linfonodi clinicamente sospetti ma con successivo agoaspirato negativo. (raccomandazione tipo A, livello di evidenza I)

46 SNB vs AD SNB neg The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial revealed no significant differences in overall survival, disease-free survival or regional control

47 SNB pos In presenza di micrometastasi nel linfonodo sentinella, la successiva effettuazione della dissezione ascellare oppure la non effettuazione della dissezione ascellare danno gli stessi risultati in termini di sopravvivenza libera da malattia a 5 anni e di sopravvivenza globale

48 Isolated tumor cells and micrometastases in a single sentinel node, were not considered to constitute an indication for axillary dissection regardless of the type of breast surgery carried out. The Panel accepted the option of omitting axillary dissection for macrometastases in the context of lumpectomy and radiation therapy for patients with clinically nodenegative disease and 1 2 positive sentinel lymph nodes as reported from ACOSOG trial Z0011 with a median follow-up of 6.3 years. The Panel, however, was very clear that this practice, based on a specific clinical trial setting, should not be extended more generally, generally such as to patients undergoing mastectomy, those who will not receive whole-breast tangential field radiation therapy, those with involvement of more than two sentinel nodes, and patients receiving neoadjuvant therapy

49 5-year SLND ALND overall survival 92.5% (95% CI, 90.0%-95.1%) 91.8% (95% CI, 89.1%-94.5%) disease-free survival 83.9% (95% CI, 80.2%-87.9%) 82.2% (95% CI, 78.3%-86.3%) local recurrence 1.6% (95% CI, 0.7%-3.3%)* 3.1% (95% CI, 1.7%-5.2%) * pz sottoposte a radioterapia e tp adiuvante Criticità dello studio Reclutamento stimato 1900 pz, reale < 891 (47% del totale, con riduzione della potenza statistica) Interruzione precoce dello studio per mancanza di effetti avversi, ovvero per avere il tasso di morti stimato (Hazard Ratio 1,3) ci sarebbero voluti fino a 20 anni di follow up Perdita delle pazienti al follow up > 17%, per mantenere una sufficiente potenza statistica le perdite al follow up devono essere < 10 % Quasi tutte le pazienti dello studio hanno eseguito terapia adiuvante (chemio 58%, ormono 46%) e radiotp whole breast (89%) Non sono stati chiariti i criteri di selezione per pazienti HER2+ e triple negative

50 IBCSG Trial di NON inferiorità 6681 casi eleggibili di cui solo 931 randomizzati Per avere una potenza statistica sufficiente l accrual doveva comprendere almeno 1960 pazienti (aprile 2001, febbraio 2010). Per aumentare l accrual nel 2006 sono stati arruolati anche i casi multicentrici e multifocali (sebbene formalmente dovevano essere sono unicentrici) e neoplasie con diametro a 5 cm (sebbene formalmente dovevano essere a 3 cm) I 931 casi randomizzati (464/467) avevano neoplasie ER/PgR +, G1-G3, con istotipo duttale e lobulare, SN+ (micromts e ITC, ma non con macromts). macromts Le ITC sono state paragonate alle micromts (!). Endopoint: Disease Free Survival, Overall Survival, Axillary recurrences Follow up 60 mesi Esclusioni: neoplasie HER2 + e triplo negative; DCIS puro, chemiotp neo-adiuvante, malattia metastatica, ascella clinicamente impegnata, malattia di Paget senza neoplasia invasiva, donne in gravidanza o in allattamento.

51 DFS a 5 anni: DLA/non DLA 88% OS a 5 anni: DLA/non DLA 98%

52 Discussione multidisciplinare

53 Tumor biology in axillary management Gene expression patterns classifies breast cancer into major subtypes: Luminal like A ER/PgR (+), HER2 (-), Ki67 < 14% B1 ER/PgR (+), HER2 (-), Ki67 > 14% B2 ER/PgR (+), HER2 (+) HER2-enriched ER/PgR (-), HER2 (+) Basal like, triple negative ER/PgR (-), HER2 (-) Breast cancer is not a single disease with variable morphological features, but rather a group of molecularly distinct neoplastic disorders, the intrinsic biological behavior of which may influence natural history and, consequently, clinical management

54 OncotypeDX measures the expression of 21 genes. genes By combining the expression levels of these genes, a quantitative recurrence score (RS) is calculated. OncotypeDX was able to stratify patients into low-, intermediate- and high-risk categories Mammaprint measures the expression of 70 genes. It calculates a prognostic score that categorizes patients under good and poor risk groups

55 QUANDO È INDICATA LA DISSEZIONE ASCELLARE ALLA LUCE DEI DATI E DELLE LINEE GUIDA ATTUALMENTE PUBBLICATE (FIM 23 gennaio 2013) La dissezione ascellare in caso di linfonodo sentinella positivo per micrometastasi può essere omessa quando la paziente soddisfa i seguenti criteri: Ecografia ascellare preoperatoria: negativa FNAC/CB di linfonodi sospetti ascellari: negative Chirurgia mammaria conservativa con successiva - radioterapia whole breast - chemioterapia adiuvante - ormonoterapia adiuvante La discussione multidisciplinare così come un adeguato consenso informato della paziente sono fondamentali in tutti i casi, ma soprattutto in quelli con neoplasie biologicamente più aggressive.

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57 Presidio ospedialiero di NOVI LIGURE Ospedale SAN GIACOMO Ambulatorio di SENOLOGIA CHIRURGICA Dott. PC Rassu, 2013