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24IN MOLECULAR PATHOLOGY AND BIOLOGY IN EARLY NSCLC
Emerging topics and ongoing research in early NSCLC (Stages I III)
S15
24IN MOLECULAR PATHOLOGY AND BIOLOGY IN EARLY NSCLC
25IN VIDEO-ASSISTED MINIMAL INVASIVE LOBECTOMY: REALITY OR THE FUTURE?
B. Besse Department of Medicine, Institut Gustave Roussy, Villejuif, France
H.J. Hansen Department of Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
During the last decade, treatment of non-small-cell lung cancer (NSCLC) has been steadily improved by optimizing cytotoxic chemotherapy and integrating targeted therapies. Further improvements could be expected by individualizing therapy based on predictive biomarkers. To date, the “quest” for the perfect predictive molecular marker has mainly been based on retrospective databases with 2 types of technology. (1) High throughput technology: Despite huge efforts and millions of Euros spent worldwide annually to identify predictive biological signatures, there has been limited progress and few ongoing prospective trials; (2) Single biomarker approach: such a biomarker can be distinguished in 3 categories of therapeutic agents: cytotoxics, tyrosine kinase inhibitors and antiangiogenics. In the ‘cytotoxic setting’, DNA repair pathways have provided the most promising biomarkers for cisplatin resistance: ERCC1 & MSH2 expression or the BRCA1 mRNA level. Other candidate biomarkers (the cell cycle regulator p27, class III b-tubulin or thymidylate synthase) had been linked to a benefit from chemotherapy. With regard to targeted therapies, specific activating mutations located in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are associated with improved response to EGFR-directed tyrosine kinase inhibitors (TKIs) in metastatic NSCLC patients. Mutations in KRAS or c-Met amplification are associated with resistance to EGFR-directed TKI therapy. In contrast, so far, treatment of early resected or irradiated NSCLC cannot be personalized based on EGFR mutations due to disappointing results. The EML4-ALK variant seems to be a good candidate for ALK inhibitors. Antiangiogenics are not indicated for the treatment of early-stage NSCLC, and no predictive biomarker has been identified so far for metastases. As many biomarkers have only been characterized in retrospective studies, prospective validation in well designed clinical trials is mandatory. Important issues are the availability of sufficient tumor material, validation of detection methods, and confirmation of a survival benefit in properly designed clinical trials. Individualized therapy based on tumor features is not a standard option for early NSCLC but may improve the outcome of patients with NSCLC in the future. Disclosure: The author has declared no conflicts of interest.
Video-Assisted Thoracic Surgery (VATS) lobectomy has become an accepted, safe and oncologically effective strategy in the surgical management of early stage lung cancer. In Copenhagen 71% of all cancer lobectomies were done by VATS in 2009. On the short term basis VATS lobectomy is associated with less postoperative pain, shorter chest tube duration, less intra-operative blood loss, less need for blood transfusion less complications, shorter length of hospital stay, shorter stay in intensive care unit (ICU) and therefore it is cost effective to the hospital. It does allow the general or pulmonary marginal patient to have a prober lobectomy with lymph node handling performed. On the long term basis VATS lobectomy is associated with less chronic pain, better preservation of lung function, earlier return to daily activities and better shoulder function. Furthermore VATS lobectomy is less immunosuppressive and seems to facilitate the deliverance of adjuvant chemotherapy. The 5 year survival rate is comparable to or maybe even better than lobectomy by thoracotomy. In selected centres VATS lobectomy now is the standard operation in early stage lung cancer and in near future it must be expected to be so throughout Europe. As the surgery is more demanding it is preferable, that it is done in high volume centres by dedicated general thoracic surgeons. Disclosure: H.J. Hansen: Teacher and advisory board member for Covidien (surgical staplers)
S15
24IN MOLECULAR PATHOLOGY AND BIOLOGY IN EARLY NSCLC
25IN VIDEO-ASSISTED MINIMAL INVASIVE LOBECTOMY: REALITY OR THE FUTURE?
B. Besse Department of Medicine, Institut Gustave Roussy, Villejuif, France
H.J. Hansen Department of Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
During the last decade, treatment of non-small-cell lung cancer (NSCLC) has been steadily improved by optimizing cytotoxic chemotherapy and integrating targeted therapies. Further improvements could be expected by individualizing therapy based on predictive biomarkers. To date, the “quest” for the perfect predictive molecular marker has mainly been based on retrospective databases with 2 types of technology. (1) High throughput technology: Despite huge efforts and millions of Euros spent worldwide annually to identify predictive biological signatures, there has been limited progress and few ongoing prospective trials; (2) Single biomarker approach: such a biomarker can be distinguished in 3 categories of therapeutic agents: cytotoxics, tyrosine kinase inhibitors and antiangiogenics. In the ‘cytotoxic setting’, DNA repair pathways have provided the most promising biomarkers for cisplatin resistance: ERCC1 & MSH2 expression or the BRCA1 mRNA level. Other candidate biomarkers (the cell cycle regulator p27, class III b-tubulin or thymidylate synthase) had been linked to a benefit from chemotherapy. With regard to targeted therapies, specific activating mutations located in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) are associated with improved response to EGFR-directed tyrosine kinase inhibitors (TKIs) in metastatic NSCLC patients. Mutations in KRAS or c-Met amplification are associated with resistance to EGFR-directed TKI therapy. In contrast, so far, treatment of early resected or irradiated NSCLC cannot be personalized based on EGFR mutations due to disappointing results. The EML4-ALK variant seems to be a good candidate for ALK inhibitors. Antiangiogenics are not indicated for the treatment of early-stage NSCLC, and no predictive biomarker has been identified so far for metastases. As many biomarkers have only been characterized in retrospective studies, prospective validation in well designed clinical trials is mandatory. Important issues are the availability of sufficient tumor material, validation of detection methods, and confirmation of a survival benefit in properly designed clinical trials. Individualized therapy based on tumor features is not a standard option for early NSCLC but may improve the outcome of patients with NSCLC in the future. Disclosure: The author has declared no conflicts of interest.
Video-Assisted Thoracic Surgery (VATS) lobectomy has become an accepted, safe and oncologically effective strategy in the surgical management of early stage lung cancer. In Copenhagen 71% of all cancer lobectomies were done by VATS in 2009. On the short term basis VATS lobectomy is associated with less postoperative pain, shorter chest tube duration, less intra-operative blood loss, less need for blood transfusion less complications, shorter length of hospital stay, shorter stay in intensive care unit (ICU) and therefore it is cost effective to the hospital. It does allow the general or pulmonary marginal patient to have a prober lobectomy with lymph node handling performed. On the long term basis VATS lobectomy is associated with less chronic pain, better preservation of lung function, earlier return to daily activities and better shoulder function. Furthermore VATS lobectomy is less immunosuppressive and seems to facilitate the deliverance of adjuvant chemotherapy. The 5 year survival rate is comparable to or maybe even better than lobectomy by thoracotomy. In selected centres VATS lobectomy now is the standard operation in early stage lung cancer and in near future it must be expected to be so throughout Europe. As the surgery is more demanding it is preferable, that it is done in high volume centres by dedicated general thoracic surgeons. Disclosure: H.J. Hansen: Teacher and advisory board member for Covidien (surgical staplers)