Lung Cancer A Surgeon's Perspective

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					        Lung Cancer:
   A Surgeon’s Perspective

           Shanda H. Blackmon, M.D., M.P.H.
                  Assistant Professor
                Department of Surgery

                        April 2009
                 The University of Houston
                  Computational Surgery

        The Methodist Hospital

 No significant affiliations or financial interests were disclosed by speaker
Presentation will not include discussion of investigational or off-label uses
                                     of product.
            Outline
• What is it?           • Invasive Staging
• What causes it?       • Survival
• Smoking               • Recurrence
• Prevalence            • Why chemo/rad/surgery?
• History               • Mortality
• Symptoms              • Types of Surgery
• Complications         • What if it is advanced?
• Role of the surgeon   • Lung Cancer Care at
• Staging                  The Methodist Hospital
• Diagnosis             • Future of Lung Cancer
• Imaging
      Lung Cancer: What is it?

• Uncontrolled growth of malignant cells in one
  or both lungs and tracheo-bronchial tree
• Arises from protective or ciliated cells in the
  bronchial epithelium
• Begins as a result of repeated carcinogenic
  irritation causing increased rates of cell
  replication
• Proliferation of abnormal cells leads to
  hyperplasia, dysplasia or carcinoma in situ
Lung Cancer: Cell Types

Non Small Cell Lung Cancer
 (NSCLC)

Small Cell Lung Cancer
 (SCLC)
 Lung Cancer: What Causes It?

• Smoking
• Radiation Exposure
• Environmental/ Occupational
  Exposure
  – Asbestos
  – Radon
  – Passive smoke
Lung Cancer: Smoking Facts

• Tobacco use is the leading cause of
  lung cancer
• 87% of lung cancers are related to
  smoking
Lung Cancer: Smoking Facts

• Risk related to:
  – amount smoked (pack years- # cigs/day
    x # yrs)
  – age of smoking onset
  – product smoked (tar/nicotine content,
    filters)
  – depth of inhalation
  – gender
 LUNG
CANCER

  18
DEATHS/HR
             Alton Ochsner
                  1919
Recalled that upon the death of a lung cancer
patient at Barnes Hospital, the chief of Internal
Medicine did the following:

                       “...insisted upon having the two
                       senior classes witness the autopsy
                       because he said the condition was
                       so rare he thought we might never
                       see another case as long as we
                       lived.”
       Lung Cancer Screening

       Cancer Death Rates 1930 – 1995
Male                              Female
     Lung Cancer 101
        USA 2002

• 169,400 new cases
     80% NSCLC
     20% SCLC
• Majority inoperable at presentation
• Overall 5 year survival 15%
• 154,900 deaths
     > Breast + Prostate + Colon
Cancer Statistics: Texas 2001

         11,000 New Cases




         10,200 Deaths
              Symptoms
•   Coughing
•   Shortness of breath (dyspnea)
•   Fatigue
•   Chest, shoulder, upper back, or arm pain
•   Repeated pneumonia or bronchitis
•   Blood coughed up in sputum (hemoptysis)
•   Loss of appetite and weight loss
•   General pain
•   Hoarseness
•   Wheezing
•   Swelling in the face or neck
          Complications

•   Fistulas
•   Bleeding
•   Bronchial Obstruction
•   Erosion into adjacent structures
Complications
   Role of the Surgeon

• Staging
• Coordination of multimodality
  treatment
• Surgical resection
• Symptom palliation
  Role of the Surgeon

• Staging
  – Staging provides a relative scale of
    disease
  – Staging will group patients with
    similar survival to identify optimum
    therapy
  Preoperative Assessment & Staging

• History and Physical
• Radiographic Evaluation
  – Minimal requirements
    • CXR, CT chest with liver and adrenal gland
  – Further evaluation
    • MRI or CT Brain, Bone scan
    • PET scan
    • Invasive Evaluation
       – Bronchoscopy, Mediastinoscopy, EUS, EBUS,
       – Biopsy (TTNA, TBNA, or Surgery)
          Lung Cancer:
        Prognostic Factors


• Stage at diagnosis

• Performance status
Chest X-Ray
CXR: Lung Cancer Screening

• Not adequate for screening for early
  disease
• Indicated to evaluate symptomatic
  patients
• CT is probably better
CT Scan
       Lung Cancer Screening
• Emphasize prevention and early screening
• I-ELCAP Trial ongoing
• The Methodist Hospital will be participating soon…
PET Scanning
PET Scanning
                PET:
change after chemotherapy & radiation
              12-2006
 PET and N2 Disease
• Unresolved issues remain
  – Utility in areas with endemic
    chronic pulmonary infections
  – Utility after induction chemotherapy
    and/or radiotherapy
  – Sole means of staging for
    protocol enrollment
               NSCLC Staging
N1   N2   N3
Mediastinoscopy
Surgical Staging
EBUS
EUS
                       NSCLC: Survival by Stage
Proportion Surviving   100

                        80

                        60

                        40

                        20

                        0
                             Stage 1 Stage II Stage III Stage IV
        NSCLC: Presentation

Distant 35%                          Local 15%
                          "Surgery"      Stage
Stage    "No surgery"
                                          I, II
  IV

               “Multimodality therapy”


                  Stage IIIa, IIIb


                Regional 50%
Five Year Survival by Stage
Clinical        Pathologic
       NSCLC: Stage, Treatment and
                Survival
I         T1-2N0            Surgery           60-70%


II        T1-2N1            Surgery           40-55%
          T3N0

IIIA      T3N1              Surgery           25%
          T1-3N2            Surgery
                            Chemo/Surgery     10-25%
                            Chemo/RT

IIIB      T1-4N3            Chemo/RT          10-20%
          T4 effusion       Chemo             <10%

          occasional T4N0M0 Surgery/Chemo
IV        M1                Chemo
                            Supportive Care   <5%
        Recurrence Patterns

                All Recurrences (%)
Stage            Local       Distant
  I               30            70
  II              21            79
IIIA              10            90


                         Socinski, Seminars in Oncology, 1999
              Life History of Lung Cancer

        yrs                 n th
                                 s
                                                  n th s              n th
    -1
      3                mo                  2 mo                     mo
2                2   0                                            1
          CXR
          CXR                        Sxs
                                     Sxs                   M.D.
                                                           M.D.              Dx
                                                                             Dx
Treatment of Lung Cancer


Surgery        Local/Regional
Radiotherapy   Control


Chemotherapy   Systemic
               Control
 Current Accepted Treatment Standards

• Stage I and II
     • Surgical resection & possible chemotherapy

• Stage III
     • Chemotherapy with radiotherapy and/or
       surgery

• Stage IV
     • Chemotherapy and/or palliative
       radiotherapy
   Lung Cancer Mortality

Time Period        5 Year Survival


1960-1963               8%

1986-1993               14%
      Type of Surgery
• Complete resection of the lobe is
  best
• Lymph node dissection should
  always be done
• Minimally invasive surgery may be
  better
• Extended resections are possible
Postoperative mortality by resection type


                               Mortality
                    Patients
                               (30 day)

   All resections    2220       3.7%

   Pneumonectomy      569       6.2%

   Lobectomy         1508       2.9%
   Segmentectomy
                      143       1.4%
   or wedge
         The North American Lung Cancer
         Study Group (LCSG) Trial
RECURRENCE - 3X increase   SURVIVAL - 30% decrease




                                  Ginsberg, Ann Thor Surg 1995
   Current recommendations for
         Stage I Disease

• Lobectomy remains the procedure of
  choice
• Lesser resections are reserved for
  patients with poor physiologic
  reserve
   Role of the Surgeon

• Coordination of multimodality
  treatment
  – Primary treatment remains surgical for
    early stage lung cancer in good
    candidates
  – Multiple phase II and some phase III
    trials suggesting the advantage of
    multimodality therapy
 Surgery for more advanced Tumors


• Many require pre-operative treatment
• All must have complete staging
  performed
• Many options are available
Before Chemo/XRT &   After
Before Chemo/XRT &   After
Before Chemo/XRT &   After
          T4 Tumors

• Potentially resectable tumors have
  include…
  – SVC involvement
  – Left atrial involvement
  – Great vessel involvement
  – Vertebral body involvement
  – Carinal involvement
               Stage IIIB Disease




R PV involvement
CPB/resection
Ro resection
         SVC Involvement
• Often require
  extensive resection
  of surrounding
  structures
  – Carinal sleeve
    resection
  – Extended
    pneumonectomy
Carinal Resection
      Advanced Lung Cancer:
          Supportive Care

• Treatment Modalities for Palliation
  – Chemotherapy
  – Radiation
• Symptom Management
  – Dyspnea
  – Fatigue
  – Pain
Superdimension Bronchus System

1.   High resolution CT scan
2.   Mapping
3.   Patient consent
4.   Placement on mat
5.   Flash drive into computer
6.   Bronch
7.   Catheter guidance
8.   Biopsy/brush/fiducial
Superdimension Bronchus System
Superdimension Bronchus System
Superdimension Bronchus System
Superdimension Bronchus System
Superdimension Bronchus System
Superdimension Bronchus System
      Superdimension Bronchus System

Case: 58 yo woman on
 the liver transplant
 service with a
 suspicious LUL
 lesion
   Superdimension Bronchus System


58 yo woman on the liver transplant
service with a suspicious LUL lesion
            Superdimension Bronchus System




Bronchoscope is inserted
           Superdimension Bronchus System




The catheter is guided through the bronchopulmonary segments based on the
Synchronized 3-d re-formatted image of the patient airway and the guided catheter
(SD Bronchus System)
       Superdimension Bronchus System




The guidant system is removed under fluroscopy and held into position
as a needle is then guided into the lesion for biopsy…
          Superdimension Bronchus System

a brush is guided for
cytology, and then…
          Superdimension Bronchus System

A fiducial marker can be placed…
Superdimension Bronchus System
 Dyspnea Management
• Assessment
• Activity planning
• Medications
  – Corticosteroids
  – Opioids
  – Oxygen therapy
• Non-traditional/investigational therapies
  – Acupuncture
  – Massage
  – Exercise
    Fatigue Management
•   Assessment
•   Activity Planning
•   Exercise
•   Sleep aids
•   Stimulants
•   Anemia management
    – Iron supplements
    – Epoetin alfa
 Pain Management
• Assessment
• Medications:
  – Opioids
  – NSAIDS
  – Corticosteroids
• Nonpharmacologic Interventions:
  –   Heat/cold
  –   Topical agents
  –   Massage
  –   Behavioral Therapy
    Management of End of Life Issues

•   Living Will
•   Medical and Legal Power of Attorney
•   Hospice
•   Code status
Lung Cancer Care at Methodist


           • Patient education
           • Mission statement
           • Palliative procedures
           • Chemotherapy ports
           • Minimally invasive surgery
           • Clinical Trials
           • Patient-centered care-
               • efficient
               • evidence-based
               • multidisciplinary
Lobectomy vs wedge: (Ginsberg)
 -3x increase in loc recurrence
 -30%decrease in survival
                                          Everything you wanted to know about                                                                  By: Dr. Shanda Blackmon

Lesser re sections reverved for poor reserve
                                                      Lung Cancer
                  N0                   N1   N2 N3 I T1-2N0 Surgery 60-70%                                                                      N2           N3
 T1               IA                  II A                                  II     T1-2N1
                                                                                   T3N0
                                                                                                    Surgery            40-55%             N1
                                                                            IIIA   T3N1         Surgery                25%
                                                                                   T1-3N2       Surgery
 T2               IB                  II B                                                      Chemo/Surg
                                                                                                Chemo/RT
                                                                                                                       10-25%

                                                                            IIIB     T1-4N3     Chemo/RT               10-20%
                                                                                     T4effusion Chemo                  <10%
  T3 II B                                            III A                  IV       M1         Chemo


                                                                          Regional lymph node inv olvement
                                                                          N0 - No l ymph nodes involved
 T4                                                          III B        N1 - Ipsilateral bronc hopul monar y or hilar nodes involved
                                                                          N2 - Ipsilateral mediastinal nodes or ligament invol ved
                                                                                                Upper paratracheal lower paratrac heal nodes
Primary tumor                                                                                   Pretracheal and retrotrac heal nodes
                                                                                          Aortic and aortic window nodes
Tis                     Carcinoma in situ
TX                      Positi ve malignant c ytol ogic                                         Para-aortic nodes, Para-es ophageal nodes
findings, no lesion obser ved                                                                   Pulmonary ligament, Subc arinal nodes
                                                                          N3 - contralateral mediastinal/hilar nodes i nvol ved or any
T1                      <3 cm and s urrounded by lung
or visc eral pl eura or endobronchi al tumor distal to                         sc alene or supr aclavicular nodes i nvol ved
the lobar bronchus
T2                      >3 cm, extensi on to the visceral            PORT:             (NEJM 1986)(Lancet 1998)
pleura, atelec tasis, or obstructi ve pneumopathy                     -Improved local control
invol ving less than 1 lung; lobar endobronchi al                     -No benefit overall survival
tumor; or tumor of a main bronchus more than 2 c m                    -Meta-analysis: -9 trials, 1966-94, 2128 pts             Improvement in the outcomes of
from the carina
T3                      Tumor at the apex, total                                        -Increased risk of death in stage I/II locally advanced NSCLC has been
atel ectasis of 1 lung; endobronchi al tumor of main                                    -but outdated techniques               demonstrated with combined
bronc hus within 2 c m of the c arina but not i nvading                                                                        modality approaches:
it; or tumor of any size with direc t extension to the               Pre-op XRT: (lancet 1995) (JCTVS 1970)                      -The “correct” strategy has not yet
adjac ent structures s uch as the chest wall                          -Some pathologic complete response                       been worked out, but several
mediastinal pl eura, di aphragm, pericardi um parietal
layer, or mediasti nal fat of the phrenic nerve                        -No benefit: resection or survival rates                options are available:
T4                      Invasi on of the medi astinal                  -Role in superior sulcus tumors ?                         -For incidentally discovered LA-
organs, incl uding the es ophagus trachea, carina,                   Pre-op Chemo:                                             NSCLC: adjuvant chemo alone
great vess els and/or heart; obstructi on of the                      -Some pathologic complete response (~10%)                  -For microscopic, “operable” N2
superior vena c ava; invol vement of a vertebral body;
                                                                      -May neutralize micrometastases                          disease,
recurrent ner ve involvement; malignant pleural or
pericardial effusion; or satellite pulmonary nodules                   -Better tolerated than adjuvant treatment                -For “inoperable” LA disease,
withi n the s ame lobe as the primar y tumor                           -May downstage, facilitating resection                  primary chemoradiation is a
                                                                     POCT: prob benefit for N2 disease                         standard of care
                        Everything you wanted to know about Esophageal cancer
                                                                                     Staging accuracy:
Staging           *initial surgery *neoadjuvant therapy *palliation
                                                                                       CT-59%                                  EUS
Stage 0         Tx (primary cannot be asse ssed)                N0, M0
                T0 (no evidence of primary tumor) or HGD                               EUS-89%
                Tis (carcinoma in situ)                                                Pet-90%
Stage I         T1 (invades lamina propria or submucosa)        N0, M0
Stage IIA       T2 (invades muscularis propria)                 N0, M0
                T3 (invades adventitia)
Stage IIB       T1/T2                                           N1 (regional nodes +) M0
Stage III       T3/T4                                           T3N1M0/ T4 any N M0
Stage IV        T4 (into adjacent structures) or any T          Any T or N/M1
  Stage IVA     M1a (cervical for upper and celiac for lower)   Any T or N
  Stage IVB     M1b (distant lymph nodes)                       Any T or N


              T2 T3 T4                            Overall 5 yr Survival = 20 %                            T1-intramucosal
                                                   T1- 48%
                                                    T2- 29%
                                                    T3- 22%
                                                    T4- 7%
                                                  Prognostic Factors:                                            balloon
                                                    grade, LN involvement
                                                    depth, mets, response to               Types of Therapy:
                                                    chemotherapy                           Trimodality therapy (Chemo + XRT + Surg)
                                                  Leak should be <6%, Mort<5%              Agents: Cisplatin, 5FU, Taxanes, oxaliplatin
Types of resections:                                                                                      etoposide, usually 2-3 cycles pre-op
 Ivor Lewis/Tanner-Lewis (transthoracic)                                                   XRT: 2-d, 3-d, and now IMRT (usually 50.4Gy)
 Orringer (transhiatal)                                                                    Wait @5 weeks to operate after neoadjuvant Tx
 3-field (abdominal + thoracic + neck)                                                     Neoadjuvent delivers prior to disrupting blood supply
 Minimally Invasive, salvage, others…                                                         -can have complete pathologic response
Plus: feeding Jej, pyloroplasty/myotomy                  R Gastroepiploic***
                                                                                           XRT to reduce tumor bulk and sterilize lymphatics
Surg contraindicated when:                                                                 Chemo to reduce circulating tumor cells
   >4LN+                                                                                   Risk F for Squamous: low SES, race, tob, ETOH
   T4 (adjacent tissue involved)                                                           High risk conditions : tylosis, achalasia, caustic strict
Types of Anastomoses:                                                                         celiac dz, plummer-vinson
Hand sewn (single versus double-layer)                                                     Risk F for Adeno: GE Reflux, Barretts
Stapled (circular versus linear stapled)                                                   Novel Therapy:
                                                                                           EMR, PDT, Stereotactic radiotherapy
           Mission Statement

Goals:
 1) New advances in treatment for patients with thoracic
 malignancies = RESEARCH

 2) Safe and evidence-based surgical interventions = MD
 conferencing, STAGING

 3) Support the patients and families with cancer =
 PALLIATIVE CARE SERVICES, HOSPICE, SPENDING
 TIME WITH PATIENTS
           What is the customary pathway for a
                         patient?


                                          Specialist
           Primary             Further
             Doc               work-up
                                                       Oncologist

Patient
referral             CXR/EGD

                                                       Rad Onc

                       Patient           Surgeon
                         Is
  @2-5 weeks         exhausted…
           Novel Approach to Patient Care…
The Thoracic Center at TMH:




                                                     Coordinates schedule for the following:
                                                                                               Pathologist

                                                                                               Radiologist
                                Record assembly/
                                Pathology review
                                                                                                Surgeon
             Screening center



                                                                                               Oncologist
Patient
referral                        Physician Visits                                                Rad Onc

                                                                                               Endoscopist

                                                                                                  Clinical trials
                                Intervention/Trial                                                coordinator

                                       Database
Denver Catheter Service
                    Port Service




*new power port for infusion
in CT and Pet (rated for higher psi)
Development of MIS Room
 VATS Lobectomy

• Taking the lung out
  without spreading the ribs
• Smaller incisions
• Less pain
• Potentially better delivery
  of chemotherapy after
  surgery
       Minimally Invasive
   Treatment of Lung Cancer



VATS exploration and wedge resections
VATS Lobectomy
Endobronchial procedures
VATS: pleural evaluation
47 yo man with R renal mass and L pleural effusion
            w congenital emphysema
VATS: pleural evaluation

Metastatic rcc:
VATS: pleural evaluation

Metastatic rcc
VATS: pleural evaluation

Metastatic rcc
VATS: pleural evaluation
47 yo man with R renal mass and L pleural effusion
            w congenital emphysema
VATS: pleural evaluation
47 yo man with R renal mass and L pleural effusion
            w congenital emphysema
VATS: pleural evaluation
             VATS: pleural evaluation
Malignant pleural mesothelioma
Management of Pulmonary Nodule

• Marginal candidates for lobectomy
  should undergo wedge resection or
  segmentectomy with node sampling
  or dissection (1B)




  Chest, ACCP 2007 Guidelines, 132(3), Sept, 2007
VATS: Wedge Resection and MLND

78 yo man from China with COPD & new LUL SPN
            s/p previous R lobectomy
VATS: Wedge Resection and MLND
VATS: Wedge Resection and MLND
VATS: Wedge Resection and MLND
VATS: Wedge Resection and MLND
Right Upper Lobe Sleeve Resection
Endobronchial Lesions
    Lung Cancer Clinical Trials
• MAGRIT - MAGE-A3: A Double-blind, randomized, placebo-controlled
Phase III study to assess the efficacy of recMAGE-A3 + AS-15 Antigen-
Specific Cancer Immunotherapeutic as adjuvant therapy in patients with
resectable MAGE-A3-positive Non-Small Cell Lung Cancer

• ENDOCYTE: A phase II study of EC145 in patients with progressive
adenocarcinoma of the lung

• Thoracic Resection- RCC: Thoracic resection of residual renal cell
cancer after molecular-targeted therapy

• ACOSOG Z4032: A randomized phase III study of sublobar resection
plus brachytherapy in high risk patients with non-small cell lung cancer
(NSCLC) <3cm

• I-ELCAP: International Early Lung Cancer Action Program: enrollment
and screening protocol.
         Mission Statement

Goals:
 1) New advances in treatment for patients
 with thoracic malignancies = RESEARCH

 2) Safe and evidence-based surgical
 interventions = MD conferencing, STAGING

 3) Support the patients and families with
 cancer
    The True Multidisciplinary Team


–   Thoracic Surgery
–   Pulmonary Medicine
–   Critical Care
–   Radiation Oncology
–   Radiology
–   Oncology
–   Palliative Care
–   Pathology
–   Research
–   Cancer Registry **
–   PA’s, Research Nurses, Research Coordinators
  Where are we Going????


• Multidisciplinary Database
• Multidisciplinary Multi-institutional trials
• Advancements in Current Care
   –   Parenchymal-sparing procedures
   –   VATS lobectomy
   –   Targeted radiation therapy vs minimal resection
   –   Mediastinal staging without incisions (EBUS + EUS)
   –   Robotic surgery???
   –   Aggressive surgical/multidisciplinary care
          Robotic Surgery
(not proven benefit and costly so far)
Where are we Going????
Lung Cancer: Conclusions

• Smoking cessation is essential for prevention of
  lung cancer.
• New screening tools offer promise for detection
  of early lung tumors.
• Clinical trials are testing promising new
  treatments.
• New treatments offer improved efficacy and
  fewer side effects.
• Treatment can palliate symptoms and improve
  quality of life.
Thank you to all of our patients…
             Outline

• What is it?           •Invasive Staging
• What causes it?       • Survival
• Smoking               • Recurrence
• Prevalence            • Why chemo/rad/surgery?
• History               • Mortality
• Symptoms              • Types of Surgery
• Role of the surgeon   • What if it is advanced?
• Staging               • Lung Cancer Care at
• Diagnosis               The Methodist Hospital
• Imaging               • Future of Lung Cancer
Questions????
         Understand the Situation:
           Research Initiatives

"What we hope to do is assemble a world
  class medical and research team that can
  provide our patients with first rate medical
  care and bring them the most advanced
  treatments."
                NSCLC Staging
Primary tumor
• Tis Carcinoma in situ
• TX Positive malignant cytologic findings, no lesion observed
• T1 <3 cm and surrounded by lung or visceral pleura or endobronchial
   tumor distal to the lobar bronchus
• T2 >3 cm, extension to the visceral pleura, atelectasis, or obstructive
   pneumopathy involving less than 1 lung; lobar endobronchial tumor; or
   tumor of a main bronchus more than 2 cm from the carina
• T3 Tumor at the apex, total atelectasis of 1 lung; endobronchial
   tumor of main bronchus within 2 cm of the carina but not invading it; or
   tumor of any size with direct extension to the adjacent structures such
   as the chest wall mediastinal pleura, diaphragm, pericardium parietal
   layer, or mediastinal fat of the phrenic nerve
• T4 Invasion of the mediastinal organs, including the esophagus
   trachea, carina, great vessels and/or heart; obstruction of the superior
   vena cava; involvement of a vertebral body; recurrent nerve
   involvement; malignant pleural or pericardial effusion; or satellite
   pulmonary nodules within the same lobe as the primary tumor
                NSCLC Staging

Regional lymph node involvement
• N0 - No lymph nodes involved
• N1 - Ipsilateral bronchopulmonary or hilar nodes involved
• N2 - Ipsilateral mediastinal nodes or ligament involved
      Upper paratracheal lower paratracheal nodes
      Pretracheal and retrotracheal nodes
      Aortic and aortic window nodes
      Para-aortic nodes
      Para-esophageal nodes
      Pulmonary ligament
      Subcarinal nodes
• N3 - contralateral mediastinal or hilar nodes involved or any scalene or
  supraclavicular nodes involved

				
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