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MCo 2011 - Slide 25 - W. Weder - Surgery

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  • 31. Non-Small Cell Lung Cancer: Stages at Presentation NSCLC patients typically present with advanced disease. Approximately one third of NSCLC patients present with early localized disease amenable to surgical treatment.
  • Mit Hilfe der Ihnen nun bekannten Stadieneinteilung werden verschiedene sich ständig ändernde Behandlungskonzepte verfolgt. Im frühen Stadium ist die kurative, d.h. heilende Chirurgie die Behandlung der Wahl, immer häufiger ergänzt durch adjuvante Substanzen im Sinne einer Chemotherapie. In den weiter fortgeschrittenen Stadien werden verschiedene Kombinationen von Chirurgie, Chemotherapie und Bestrahlung angewandt. In den späten Stadien, v.a. mit entfernten Lymphknoten und Organmetastasen gilt es in erster Linie die Lebensqualität des Patienten zu optimieren, auch hier kommt teilweise die Chirurgie zum Einsatz.
  • Die Resektion des Tumors wird in der Regel als Standardresektion im Sinne einer Entfernung der kompletten anatomischen Einheit, z.B. eines Lungenlappens, durchgeführt. Zusätzlich werden auch die mediastinalen Lymphknoten mit entfernt. Je nach Lage und Ausdehnung des Tumors sowie Allgemeinzustand des Patienten wird die Resektion limitiert (sehr frühes Stadium, schlechte Lungenfunktion) oder erweitert mit Entfernung angrenzender Strukturen (Brustwand, grosse Gefässe) erfolgen. Auf die zwei letzten Techniken gehe ich noch genauer ein.
  • Transcript

    • 1. 10th ESO-ESMO Masterclass in Clinical Oncology 02-07 April 2011, Ermatingen Walter Weder MD Professor of Surgery University Hospital Zurich NSCLC: Surgery
    • 2. 59 y, female, 40 py, incidental finding on chest X-ray Case 1
    • 3. Questions
      • What is your diagnosis?
      • Further staging?
      • Lobectomy or sublobar resection?
      • Radiotherapy
      • Adjuvant therapy indicated?
    • 4. NSCLC - stages at presentation Fry, Cancer 1996 31% Stage III 38% Stage IV 24% Stage I 7% Stage II
    • 5. Stage-dependent survival for NSCLC
      • Stage I 54-80%
      • Stage II 38-60%
      • Stage IIIA 10-30%
      • Stage IIIB <10%
      • Stage IV <5%
      Tsuboi, World Conference IASLC 2009 5-y survival after state-of-the-art treatment
    • 6. Personalized therapy Paradigm shift from empiric to integrated therapy TNM Surgery Radiotherapy • Local extension • Timing • Undetermined adapted from D. Gandara, World Conference IASLC 2009
    • 7. T 1- 3 N 0 Curative surgery ± adjuvant therapy T 1 -3 N 1 T 1 -3 N 2 Chemo-/(radio-)therapy and surgery T 4 N 0 - 1 T 1 -2 N 3 T 4 N 3 M 1 Palliative therapy Lung cancer - treatment concepts
    • 8.
      • Standard lobectomy (pneumonectomy) + mediastinal lymphadenectomy
      • Modifications:
      • Minimally invasive lobectomy (VATS)
      • Sublobar resections
      • Sleeve resections
      Surgical procedures
    • 9. 2-4 incisions 30 – 70% of all lobectomies in experienced centers may preserve immunologic response and better compliance for adjuvant therapy Minimally invasive (VATS) resections
    • 10. Limited resection vs lobectomy Lung Cancer Study Group: Ann. Thorac. Surg., 60, 615, 1995
    • 11. Limited resection vs lobectomy Nakamura H. et al. Brit. J. Cancer 2005; 92, 1033
    • 12. The role of Tumor size Okada et al. J. Thorac. Cardiovasc. Surg. 2005; 129, 87 5-Year-survival according to tumor diameter < 20mm 21-30 mm > 30 mm Lobectomy 92% 87% 81% Segmentectomy 96% 85% 63% Wedge resection 86% 39% 0%
    • 13. Tumor histology and Grading Nakamura H. et. al., Lung Cancer, 2004; 44, 61 5-Y- survival after sublobar resection p-value Adenocarcinoma (n=76) 66 % Squamous cell carcinoma (n=21) 59 % 0.75 G1 (=52) 84 % G2-3 (n=45) 46 % 0.001
    • 14. Consequences of limited resection
      • Small functional advantage after limited resection (<10 %)
      • More local recurrences after sublobar resections
      • Small survival disadvantage (3.6%)
    • 15. Lung saving (sleeve-) resections
    • 16. T-stage
    • 17.  68000 NSCLC,  1000 SCLC World Conference IASLC 2009 New staging system
    • 18. Chest wall infiltration ?
    • 19. Chest wall infiltration
      • important only for planning of the surgical procedure
      • 5-year survival up to 40% in T3N1with adjuvant chemotherapy Burkhardt, JTCVS 2002
      • similar success rates in pancoast tumors following induction radio-chemotherapy and complete resection Rusch, JCO 2007
    • 20. Pancoast tumors (superior sulcus tumors) PET/CT for staging (mediastinum, distant metastases) Determination of the radiation field Tumor of the apex of the lung with possible infiltration of the chest wall brachial plexus, stellate ganglion, ribs, vertebae < 5% of all bronchogenic carcinoma
    • 21. S.P.1940 cT3N2 N-stage Microscopic infiltration or bulky multilevel disease?
    • 22. Lymph node status predicts outcome Naruke, Ann Thorac Surg 2001
    • 23. Survival of patients with resected N2 Andre, JCO 2000 Subgroups Patients 5-yr Survival Minimal N2 - One Level - Multiple Levels Clinical N2 - One Level - Multiple N2 354 244 78 332 118 122 29,5% 34% 11% 7% 8% 3%
    • 24. Incidental (occult) N 2 disease adjuvant treatment
      • adjuvant cisplantin – based chemotherapy is recommended
      • adjuvant postoperative radiotherapy should be considered to reduce local recurrence
      ACCP Guidelines, Chest 2007
    • 25. N-stage Multilevel N 2 disease – primary surgery not indicated
    • 26. The stage III disease Pts with NSCLC, IIIA, pN2 resectable CT* + RT (61 Gy) CT* + RT (45 Gy) Surgery * Cisplatin 50 mg/m 2 d1/8/29/36 Etopophos 50 mg/m 2 d1-5, d29-33 CT* N=202 N=194 Albain, Lancet 2009
    • 27. RTOG 9309: Efficacy Albain, Lancet, 2009 0 12 24 36 48 60 0 25 50 75 100 CT/RT/C CT/RT Survival probability (%) Death /total 145/202 155/194 p=0 . 24 RR=0 . 87 (0 . 70; 1 . 10) Months 0 12 24 36 48 60 0 25 50 75 100 CT/RT/S CT/RT Survival probability (%) Death /total Months 57/90 74/90 18% 36% 5- year S 22 months 34 months MS CT/RT CT/RT/S p=0 . 002
    • 28. RTOG 9309: operative mortality
      • Lobectomy versus pneumonectomy
      • Mortality (n=15):
        • Lobectom y 1% versus pneumonectom y 26%
        • Right pneumonectom y (n=11 ; 79%)
        • Etiology: ARDS (n=11)
      Albain, Lancet, 2009
    • 29. Pneumonectomy after neoadjuvant chemo- and radiotherapy
      • 176 patients, 122 males (69%) 56 years (33-74)
      • 3 cycles of cisplatin-doublets (n=35, 20%)
      • 3 cycles of cisplatin-doublets (n=141, 80%)
      • +45 Gy (1.5 Gy, bi-daily) to primary tumor and mediastinum
      • (fourth cycle cisplatin-doublets in Essen)
      • pneumonectomy (n=176), 86 (49%) right
      • 138 (78%) extended
      Weder JTCS 2010
    • 30. Morbidity and Mortality
      • 6 patients died (3%) (30 d mortality)
      • (3 pulmonary embolism, 2 ARDS, 2 cardiac failure)
      • 23 major complications (13%) in 22 patients
      • 6 pneumonia / ARDS
      • 5 broncho-pleural fistula (4R, 1L)
      • 5 empyema
      • 3 pulmonary embolism
      • 2 hemothorax
      • 1 heart failure
      • 1 gastric hernia
      Weder, JTCS 2010
    • 31. Survival according to clinical stage Weder, JTCS 2010
    • 32. Patient received 2 cycles of induction with CDDP/GEM. Tolerated chemotherapy very poorly Restaging with PET/CT SD ( ± PD) MRI of brain without metastasis 65 year old obese (BMI 25) female of RLL with metastases to lymph nodes # 10, 7, 4 R (tracheal infiltration)
    • 33. Patient is alive after 5 years with NED, assessed clinically and by CT
    • 34. ‘ Resectable N 2 ‘ – which questions have to be answered?
      • Is ‘N 2 ‘ technically resectable?
      • Is surgery complete?
      • Is surgery indicated from an oncological point of view?
      • What is the risk for the patient?
      • Does the patient tolerate pulmonary resection?
      •  risk-benefit ratio
    • 35. Role of highest level N 2 node Sakao, Ann Thorac Surg 2006
    • 36. Single vs multilevel N 2 Decaluwé, EJCTS 2009
    • 37. Role of mediastinal downstaging Betticher et al. , JCO 2003
    • 38. Take home message I
      • NSCLC remains to be the cancer with the highest cancer related mortality
      • Appropriate clinical and pathological staging (including tissue diagnosis) is key to an “individualized“ treatment
      • Lobectomy with systematic mediastinal lymph node dissection is the standard surgical procedure for most T 1 – T 3 , N 0 – N 1 tumors
      • Minimal invasive lobectomy by VATS is performed more and more frequent in specialized centers since morbidity and mortality is reduced and adjuvant therapy better tolerated
    • 39.
      • Adjuvant chemotherapy is indicated for “fit patients“ with stages ≥ T 2 , N 1
      • Patients with ipsilateral mediastinal lymph node metastasis (N 2 disease) are best treated with neaoadjuvant chemo(-radio)therapy followed by surgery preferentially as part of “clinical trial“
      • surgical resection after induction chemoradiotherapy should be limited to a lobectomy - whenever possible
      • surgical resection for NSCLC should be complete and the treatment related mortality within an acceptable range.
      Take home message II

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