( Chest Surgery Associated Professor Kao Eing-Long )

Tel: 3121101 ext: 6306

E mail: kaeil@cc.kmu.edu.tw

( Respiratory Disease )( Non Small Cell Lung Cancer )

( Learning Object ) Classification of Lung Cancer : SCLC vs NSCLC. Diagnosis / Tumor Markers. Grading / Extent / Staging. TMN Classification / Performance Status Scales. Therapeutic Decisions. Pre-op Pulmonary / Cardiovascular Evaluation.Surgery Risks / Chemotherapy / Radiation Therapy. New Diagnostic Tolls & Treatment Strategies.

New Diagnostic Tools & Treatment StrategiesTOPICS - New Diagnostic ToolsMolecular Biology / Biomarkers Early detection. Prediction of sensitivity to CT/RT Detection of minimal residual disease / relapseResults of low dose spiral CT scan screening programsNew diagnostic toolsPET, LIFE Bronchoscopy, ( Lung Imaging Fluorescence Endoscope )Virtual CT bronchoscopy

Etiology: smoking, occupational exposure .. , , air pollution, genetic factor, scaing

TOPICS - Treatment Strategies

Role of Surgery

Minimally invasive thoracic approaches.

Surgical staging.

Nodal sampling / radical dissection.

Sentinel node.

Limited resection for very early disease.

Management of spiral CT scan lesions below 1 cm

Role of Radiotherapy

3D Conformal Radiotherapy,

Intensity Modulated Radiation Therapy ( IMRT ).

Images Guided Radiation Therapy ( IGRT ).

DIBH.

Stereotactic Precision Radiotherapy.

Proton Therapy

Chemopreventive agents

COX-2 inhibitors,

Glucorticoids.

Retinoid resistance and new retinoids,

Gene strategies,

Bioadjuvant therapies,

Systemic vs. Pulmonary delivery

New treatment approaches

Pharmacogenomic. New cytotoxic agents, ( Paclitaxel - Taxol )

Targeted ( EGFR ) biologic therapies.

Apoptotic agents, ( p53-cs17, Rb-cs13, )

Hybrid cytotoxic-cytostatic approach,

Modulators ( Interferon, Cytokin ) and

revertants of drug resistance,

Vaccines

Laboratory TestsSpecial biochemical studiesBlood surveyCalciumLDH

Hormone ACTH, AVP, ADH (SIADH), PTH

Tumor markerCEA TPA CYFRA21 SCC NSE p34 Biology, Genetic Changes p35 Oncogens, Tumor Suppressor Genes,

p36 Growth Factors.., p37 & p38 , , , Oncogenes & GH.

Pre-op Pulmonary / Cardiovascular EvaluationEvaluation Of The Respiratory System

Clinical Evaluation, Exercise Capacity, Spirometry, Arterial Blood Gas Analysis, Regional Pulmonary Studies ( Including LPT ), Pulmonary Circulation (TUPAO)..

Evaluation Of Cardiovascular SystemOther Perioperative Therapeutic ConsiderationsPrevention Of CV ComplicationsPrevention Of Respiratory Complications

Risk FactorsAge, Respiratory Diseases, Abnormal Pulmonary Function, CV Disease ( Cardiac Function Test ) Extent of Resection, General Risk Factors ( Nutrition, Alcohol & Smoking, Obesity )

Common Physiologic DisturbanceIncreased Pulmonary Arterial Venous ShuntingAtelectasisUneven Disturbance of Ventilation & PerfusionIncreased Lung WaterDiffusion BlockIncreased Pulmonary Dead SpaceIncreased Work of BreathingDecrased oxygen Transport in The BloodDecreased Resistance to Infection

PREOPERATIVE ASSESSMENT OF PATIENTSUNDERGOING LUNG RESECTION FOR CANCERSURGERY FOR NSCLC

SURGICAL ADJUVANT THERAPY OF NSCLCNSCLC: DEFINITIVE RADIOTHRAPY & COMBINED MODALITY THERAPY

THE ROLE OF CHEMOTHERAPY IN THE MANAGEMENT OF DISSEMINATED NSCLC TREATMENT OF SCLC

SUPERIOR SULCUS TUMORSSVC SYNDROME: AN ONCOLOGIC EMERGENCY

The Surgery Procedure vs. Risk Factors

Dependent On The Nature, Conduct,And Extent Of Operation

Normal Lung Function After Operation

Lung Volumes And Ventilatory PatternsGas ExchangePulmonary Defense Mechanisms

Dependent On The Conduct Of The Procedure

Will Suffer Respiratory Complications.

Airway Defense Abolish / Reduce; Airway Monitor

ARDS ( Fluid Overload / Blood Massive Transfuse )

Dependent On The Extent Of The Operation

Lung Function After Pneumonectomy

Risk Of Concomitant Cardiac & Pulmonary Operations

CANCER PATIENT MANAGEMENTThe diagnosis of cancer requires a histological proof of malignancyThe treatment is mostly based on the extension of the disease and on the histology. Performance status, age and history are also critical factors for establishing the treatment strategy.

TUMOR EXTENT STAGINGThe extent of the disease is one of the key parameters for treatment orientation. In case of localized disease the resectability of the tumor and the operability of the patient are also pivotal.

TNM CLASSIFICATIONThe U.I.C.C (Union Internationale Contre le Cancer) has set up on international classification based on tumor size (T), lymph node involvement (N) and the presence (or not) of distant metastasis (M). The prognosis is better if the tumor id small and if there is no lymph node involvement and no distant metastasis.

TUMOR MARKERS/EXAMPLESIn some tumors, the evolution of tumor markers over time should allow the assessment of treatment efficacy and the early detection of relapse.

PERFORMANCE STATUS SCALESThere are several performance status scales. The Karnofsky goes from 100 (normal) to 0 (dead). The E.C.O.G. from 0 (normal) to 5 (dead). These scales evaluate the degree of autonomy for current activities.

RADIATION THERAPY / DEFINITION OF VOLUMEThe target volume encompasses the tumor volume plus a margin to take into account the possibility of microscopic extension.The treatment volume encompasses the target volume plus a security margin.

TYPES OF IONIZING RADIATIONSGamma Rays (=photons, =X rays) are the most penetrating rays. The maximum dose of these rays is delivered 0.5 cm beneath the skin surface. B particules are electrons. The dose of radiation delivered by electrons diminishes rapidly with tissue depth. A particules are helium nuclei. They deliver their radiation dose at a defined tissue depth.

CANCER RADIATION SENSITIVITYThe tumors are classified in different categories based on their sensitivity to radiation. The goal of radiotherapy is to deliver enough radiation to sterilize every tumor type whatever the radiation sensitivity is . The dose depends also on the tumor extent and the histological nature of the cancer.

Guidelines on Treatment of Stage IIIB Non-small Cell Lung Cancer2003;123;211S-225S ChestIntroduction

Stage IIIB T4 tumors, any N, M0 N3 tumors, any T, M010-15% of the patient at the time of diagnosis5 year survival 3~7% for patients with Stage IIIB

Guidelines on Treatment of Stage IIIB Non-small Cell Lung CancerTreatment options depend on the extent of diseaseSurgery alone in selected patientsSurgery after induction therapy in selected patientsCombination of chemotherapy and radiotherapyEvidence based guidelines is based on an extensive review of medical literatures8 guidelines, 1 randomized phase III trail in England and abstracts

Limited role of Surgery Surgery alone may be indicated for carefully selected situationsT4N0-1 satellite tumor nodule within a primary tumor lobe 20% 5 year survivalT4N0-1 main carinal involvement, carinal resection with or without pulmonary resection incrased risk of local recurrence but 20% 5 year survival

Surgical Recommendation1. Patients with clinical T4N0 NSCLC due to either satellite tumor nodule(s) in the same lobe or carinal involvement should be evaluated by a thoracic surgeon for possible resection. (Fair/B)2. For patients with stage IIIB NSCLC due to T4 (excluding Pancoast tumors) or N3 disease, treatment with neoadjuvant chemotherapy or chemoradiotherapy followed by surgery has been explored in limited phase II trials.

Combination Chemoradiotherapy Recommendation At this time, there are no phase III trial data available to document that surgery adds to survival; therefore, this approach should not be considered as standard therapy. (Poor/I)

3. For patients with stage IIIB disease without malignant effusions, PS 0 or 1, and minimal weight loss ( 5%), combined chemoradiotherapy should be the standard of care. (Good/A)4. In patients with stage IIIB NSCLC and PS 2 or those with substantial weight loss ( 10%), combined modality treatment could be used after careful consideration. (Poor/C)

Altered Fractions Of Radiotherapy5. For epithelial tumors. The clinical effectiveness of radiation: total dose /unit time. Multiple daily fractionsreduction in late tissue damage. 6. Hyperfractionation= the use of 2 or more fractions daily of smaller-than-conventional fraction size. 7. Accelerated RT: the use of 2 or more fractions of standard fraction size daily to the same conventional total dose, increasing the numbers of fractions per week, shortening the overal treatment time. 8. Hyperfractionated accelerated RT: 2 or 3 fractions of smaller fraction size daily, delivered over a shorter period of time than conventional therapy. To reduce long-term normal tissue damage.

Altered Fractions Of RadiotherapyA randomized phase III trail in England:Continuous hyperfractionated accelerated RT (CHART) VS standard RT(60 Gy/ 30 Fx)1-year survival: 63% : 55%; 2-year survival: 29%: 20%Overall: 22% reduction in the relative risk of death. Acute esphagitis. No difference at late morbidity. Phase III trial of HART: stopped. No data are available concerning the combination of CHART and chemotherapy.

( Summary ) Non Small Cell Lung Cancer (NSCLC ) Diagnosis / Tumor Markers / TMN Classification. Pre-op Pulmonary / Cardiovascular Evaluation. Role of Surgery vs Risks / Pulmonary Defense Mechanisms Role of Radiotherapy / Combination Chemoradiotherapy . SUPERIOR SULCUS TUMORS.New Diagnostic Tolls & Treatment Strategies Chemopreventive agents / Bioadjuvant therapies / Pharmacogenomic. http://www.kmuh.org.tw/www/thorax/index.htm