Management of lung cancer

By: Dr: Abdul-Aziz Assen (GSRIV)

Moderator: Dr Samuel
• Content
• Introduction
• Staging

• Treatment option of:

• Early stage (I and II) NSCLC

• Locally advanced (III) NSCLC

• Metastasis stage (IV ) NSCLC

• Lung carcinoid

• Reference
• EPIDEMIOLOGY OF LUNG CANCER
RISK FACTORS
• Tobacco smoking
• accounts for 80%-90% of all lung cancer incidence
• 20- to 30-fold increased risk in smokers compared to non-smokers.
• a lag period of approximately 20 years between the exposure and disease
occurrence.
 RX non-small cell lung cancer (NSCLC)
• The optimal management of patients is dictated by :
• tumor
• characteristics,
• clinical stage, and
• the patient’s underlying physiologic status.
Clinical
• early stage IA–IIB NSCLC
• anatomic lung resection with mediastinal lymph node sampling or dissection.
• adjuvant chemotherapy (high risk stage I ,stage II) following complete
resection.
• advanced NSCLC
• Surgery plus aduvant chemotherapy for selected pnt
• loco regionally advanced (stage IIIB)
• are best managed by chemoradiation
• systemic metastases (stage IV)
• chemotherapy only
• There is no proven benefit for the routine use of surgery in patients with advanced NSCLC.
NON–SMALL CELL LUNG CANCER
TREATMENT: EARLY STAGE
• surgery
• R0 surgical resection is the procedure of choice
• definitive RT
• Adjuvant radiotherapy :
• For patients who undergo resection
• are unable to obtain a negative margin, R1 resection, there is a role for postoperative
chemotherapy with radiation
• utilizing a multidisciplinary tumor board to provide optimal,
multimodality treatment options for patients.
• often involving thoracic surgeons, pulmonologists, medical
oncologists, radiation oncologists, and interventional radiologists.
• the role of surgery and the judgment of thoracic surgeons :
• remains critical as surgical resection remains the mainstay therapy for stages
I–IIIA
• one important goal of multimodality therapies at early stage:
• is the prevention of locoregional recurrence.
• potential adjuncts to surgical resection:
• intraoperative fluoroscopic tumor localization,
• brachytherapy,
• local radiation, and
• adjuvant chemotherapy.
• Multimodality Therapy for Stage I NSCLC
• Surgical resection ± brachytherapy ( margin)
• Brachytherapy
• is a method by which radioactive iodine-125 (I125) seeds are incorporated into the lung staple line after surgical resection, with either
suture or a manufactured Vicryl mesh impregnated with I125 seeds
• Intraoperative fluoroscopic localization with preoperative transthoracic or transbronchial gold fiducial
marking
• simple multidisciplinary technique can be used to identify:
• small, semisolid, and difficult-to-identify lesions
• the pulmonary nodule was successfully resected in 98% of cases (57 of 58 patients),
• 20% of whom were identified as having primary lung cancer.
• gProcedure-related complications occurred in three patients, and
• included fiducial embolization, fiducial migration, and intraparenchymal hematoma
• Potentially adjuvant platinum-based chemotherapy for tumors >4 cm
• Alternatives to resection for high-risk candidates
• Stereotactic body radiotherapy
• Radiofrequency ablation
• Results from LCSG showed :
• local recurrence rates of 7% after lobectomy and 18% after sublobar resection
for stage I lung cancer.
• OS rates with conventional radiotherapy :
• have historically been quite poor (5% to 30%) when compared with surgical resection
• SBRT
• image-guided, focused delivery of high dose radiotherapy while compensating for respiratory tumor motion.
• local control rates in non operative patients reported as high as 90%.
• distant recurrence occurred in 22% patients
• The Radiation Therapy Oncology Group (RTOG) 0236 trial :SBRT at a dose of 54 Gy
• enrolled 59 patients with peripherally located NSCLC <5 cm treated
• Results of this study showed:
• excellent rates of local control with only one failure,
• an OS rate of 56%, and
• a 3-year disease free survival rate of 48%.
• SBRT is considered the standard primary therapy for early stage NSCLC in non operative patients.
• Adjuvant radiation therapy for stages I and II is generally not
recommended as there has been non identified benefit.
• the majority of studies agree that there is no role for adjuvant
chemotherapy for T1 (<3 cm) N0 NSCLC
• Multimodality Therapy for Stage 2 NSCLC
• Mediastinoscopy, thoracoscopy, and endobronchial ultrasound for
mediastinal staging
• Surgical resection
• Adjuvant platinum-based chemotherapy
• Neoadjuvant platinum-based chemotherapy in selected cases
• Mutation targeted therapy in clinical trials
• adjuvant chemotherapy therapy
• optimal chemotherapy regimen for NSCLC remains to be determined
• 5.4% OS benefit
• 24% of patients in the LACE meta-analysis:
• were able to complete only two or fewer cycles of chemotherapy out of the prescribed
three to four cycles
• most commonly due to patient refusal or toxicity.
STAGE IIIA NON-SMALL CELL LUNG CANCER T1
and T2 with N2 and T 3 with N1 and T4 with 0 and 1
• Clinical stage :
• Concurrent neo adjuvant chemo radiotherapy plus surgery
• 5-year survival low (5% to 15%) in such patients
• pathologic :surgery plus adjuvant chemo radiotherapy
• occult N2 metastases incidentally noted on pathologic examination after
surgical resection
• 5-yeasurvival (25% to 35%)
STAGE IIIB (T1 and T2 with N3 and T 3
and T 4 with N2)
• The overall median survival of patients with metastatic disease is less than
10 months.
• There is little role for resection for patients with advanced stage lung
cancer.
• in patients with N3 disease:
• there is no role for surgical resection
• should be evaluated for definitive chemotherapy.
• Patients with acute, life-threatening hemoptysis or recurrent,
postobstructive pulmonary infections can be:
• considered for radiation therapy if quality of life can be preserved postoperatively.
Stage I and II
• Option of managements
• Surgery: treatment of choice
• Adjuvant therapy
• Adjuvant chemotherapy for patients with large stage IB, II and III A tumor
• ADURA (NCT02511106)phase III trial: Adjuvant target therapy
• for patients with stage IB,II and III A tumors with EGFR mutations
• Have improved DFS with osimerrtinib 80 mg po daily for 3 year.
• Os: data are immature and follow up if going. Radiation therapy for patients who cannot
have surgery or choose not to have surgery
• Multimodality Therapy for Stage IIIB and Stage 4 NSCLC
• Palliative chemotherapy
• Tube thoracostomy or talc pleurodesis for malignant effusion
• Targeted therapies
• Palliative and hospice care
• Surgical resection for select oligometastatic disease synchronous or
metachronous isolated :
• brain metastasis,
• adrenal lesion, or
• satellite pulmonary nodule in contralateral lung
• followed by adjuvant chemotherapy,
• Resection of the primary NSCLC and brain metastasis, followed by adjuvant chemotherapy,:
• median survival in retrospective case series has been reported as high as 24 months
• with a 5-year survival of 20%.
• Surgery option:
• Pneumonectomy ,Lobectomy,segmental or wedge or sleeve resection
• Pneumonectomy V lobectomy
• Mortality rate is 5%to 8% and 3% to 5% respectively in addition to immediate and age
related postoperative mortality
• lung cancer resection combined with complete ipsilateral mediastinal lymph
node dissection (CMLND) verses resection and lymph node systematic
sampling
• No difference in over all sevival,disease specific sevival and local and reginal
recurrence. For pnt with stage I,II and IIIA NSCLC
• Air leak lasting more than 5 days significantly more common in CMLND
NON–SMALL CELL LUNG CANCER
TREATMENT: EARLY STAGE
• are managed with surgical resection or
• definitive radiation therapy (RT)
RIGHT PNEUMONECTOMY
• RIGHT HILAR DISSECTION
• First
• the lung is then rotated posteriorly, and

• the pleura is incised posterior to the course of the phrenic nerve, which usually passes close to the base of the superior pulmonary vein.

• The phrenic nerve is carefully and gently mobilized anteriorly to expose the superior pulmonary vein and inferior
pulmonary vein.

• Next
• the right upper lobe is then rotated more inferiorly

• to provide a better view of the superior aspect of the hilum and allow complete exposure of the truncus anterior branch.

• Finally
• the lung is rotated anteriorly, and the right main bronchus, right upper-lobe bronchus, and right bronchus intermedius are exposed.
• After hilar dissection,
• the lung is rotated inferiorly and posteriorly, and
• the main trunk of the right pulmonary artery is exposed as it exits the
pericardium posterior to the vena cava.
• The ligation and division of the right pulmonary artery can be
accomplished using
• a vascular stapler or
• dividing the vessel between clamps and oversewing with 3-0 non absorbable
sutures
• Next, the lung is rotated posteriorly
• the superior pulmonary vein is mobilized on its superior and inferior aspects
with blunt and sharp dissection then:
• encircled, ligated, and divided using a vascular stapler.
• Division between clamps and over sewing with 3-0 non absorbable sutures is also
acceptable.
• The lung is then retracted superiorly
• the inferior pulmonary vein is dissected, ligated, and divided in the same
manner as the superior pulmonary vein .
• After dividing the major vessels
• the lung is retracted anteriorly and the subcarinal lymph nodes are mobilized.
• The bronchial artery originates at the apex of the carina anteriorly and should
be clipped.
• The remaining peribronchial tissues
• are then mobilized distally with blunt and sharp dissection so that the bronchus is
exposed within 1 cm the carina.
• A tick tissue stapler
• is oriented so as to approximate the anterior cartilaginous and posterior
membranous walls and the bronchus is divided distal to the staple line.
• On the right side, the coverage of the pneumonectomy stump:
• with viable tissue is preferred, especially if the patient has received or will
receive chemotherapy and/or radiotherapy.
• The ideal tissue for coverage
• is either a rotated intercostal muscle flap harvested during entry into the
chest or
• a pericardia! fat pad rotational flap.
• The flap is secured with carefully placed 4-0 polypropylene sutures.
RIGHT UPPER LOBECTOMY
• Two branches of the pulmonary artery- enter the right upper lobe
• the truncus anterior
• and posterior ascending arteries
• The truncus anterior
• is the first branch of the right main pulmonary artery and
• is typically a large branch that immediately bifurcates into two or three
branches.
• Once the truncus anterior is exposed, it is either suture-ligated and divided
or transected with a vascular stapler.
• The posterior ascending artery
• typically originates from the interlobar pulmonary artery opposite the
right middle lobe branch.
• To expose the posterior ascending pulmonary artery,
• the interlobar fissure is dissected, and the pulmonary artery is exposed at the
junction of the major and minor fissures.
• All the branches are dissected including t he middle lobe, posterior ascending,
superior segmental, and basilar segmental arteries
• The posterior ascending artery is often partially obscured by :
• a level 11 interlobar lymph node and
• the posterior segmental branch of the superior pulmonary vein, which
traverses the fissure towards the superior pulmonary vein.
• If the exposure is adequate
• the posterior ascending branch can be ligated and divided or stapled.
• If the exposure proves difficult
• completion of the fissure between the upper lobe and lower lobe can sometimes
facilitate this exposure.
• This is facilitated by dividing the pleura in the posterior hilum along the lateral edge of the
bronchus intermedius.
• A level 1 1 lymph node located between the right upper-lobe bronchus and the
bronchus intermedius:
• is then removed to allow exposure of the posterior ascending branch of the pulmonary artery.
• A right-angle clamp can be passed from the interlobar fissure:
• between the superior segmental branch of the pulmonary artery and the posterior ascending
pulmonary artery to the posterior hilar dissection.
• The fissure can then be completed with either a medium or thick tissue staple
Mx of stage I and II con…

• Surgical option are:

• Sub lobar resection:

• wedge resection and segmentalectomy

• LOBECTOMY,

• BILOBECTOMY,

• SLEEVE RESECTIONS

• PNEUMONECTOMY

• Plus
• mediastinal complete lymph node dissection or systematic lymph node sampling
Lobectomy
• Lobectomy is also the choice for peripheral tumor resection, while
• pneumonectomy is generally reserved for centrally located tumors..
• Prior to resection
• an endobronchial double-lumen tube is placed into the bronchus opposite to
the side of lobectomy to initiate one-lung ventilation
• The anesthesiologist isolates the lung, and
• the pleural space:
• is entered cautiously to avoid any air leaks from inadvertent parenchymal
injury.
Anterior view of right hilum Posterior view of the right upper lobe with the airway
with the lung retracted divided. (REPRINTED WITH THE PERMISSION OF THE CLEVELAND CLINIC
FOUNDATION.)
posteriorly and the vein to the
upper lobe divided. (REPRINTED WITH
THE PERMISSION OF THE CLEVELAND CLINIC
FOUNDATION.)
FIGURE 72-5 View of the
dissected right pulmonary artery
in the fissure. (REPRINTED WITH THE PERMISSION
OF THE CLEVELAND CLINIC
FOUNDATION.)
FIGURE 72-6 Posterior view of the left hilum, FIGURE 72-7 Anterior view of the left hilum, showing the divided
showing the left main superior pulmonary vein and apical pulmonary artery branches.
(REPRINTED WITH THE PERMISSION OF THE CLEVELAND CLINIC
pulmonary artery, arch of aorta, and left main FOUNDATION.)
bronchus. (REPRINTED
WITH THE PERMISSION OF THE CLEVELAND CLINIC FOUNDATION.)
Technical Aspects of Lobectomy
• The different lobes of the lung
• have defining characteristics that distinguish the operative technique required
for resection
• incision
• posterolateral thoracotomy because
• it allows greater exposure
• and maneuverability for the surgeon.
• Anterolateral thoracotomy, median sternotomy except for the left lower lobe,
and
• muscle-sparing lateral or axillary thoracotomy
MOBILIZATION OF THE LOBE
• The pleural cavity is entered through:
• the fifth intercostal space for upper lobectomy or any central lesion.
• the sixth space is acceptable for peripheral lower lobe tumors.
• If adhesive pleuritis is anticipated:
• entrance through the bed of the resected fifth rib:
• allows for more expeditious mobilization of the lung, either in the intrapleural or extrapleural plane.
• Web-like avascular adhesions:
• are managed by finger dissection and a sponge stick;
• For vascular adhesions: cautery is applied
• Inflammatory and cavitary lesions adherent to the parietal pleura
• are mobilized in the extrapleural plane.
• tumor is determined :
• tumors adherent to the parietal pleura:controversial
• en bloc resection of lung and chest wall in this situation
• to be fixed to the chest wall during this dissection:
• the extrapleural approach is abandoned and en bloc resection is performed.
• After mobilization of the lung:
• the mediastinal pleura is incised around the hilum, the pathology is
evaluated, and node sampling is performed as indicated.
• Exploration and Mobilization of the Lung
• MOBILIZATION OF THE LOBE
• FISSURE DISSECTION
• MANAGEMENT OF LOBAR VESSELS
Exploration and Mobilization of the Lung
• The chest
• is carefully explored to identify any unexpected pleural metastasis.
• All lobes of the lung
• are palpated to identify the location of the lesion, confirm its resectability, and rule out any
other lesions.
• The inferior pulmonary ligament
• is taken down using electrocautery, and
• the hilum of the lung
• is freed up circumferentially with division of the mediastinal pleura.
• Electrocautery
• can be used on the posterior aspect of the hilum,
• but care must be taken anteriorly to avoid thermal injury to the phrenic nerve.
Management of the Hilar Vessels
• Hilar dissection begins
• with identification and dissection of the three primary vascular structures:
• the pulmonary artery,the superior pulmonary vein, and the inferior pulmonary vein.
• Sequential transection of:
• artery, followed by vein, followed by airway is the safest method.
• This prevents :
• inadvertent injury to the pulmonary artery during encirclment of the airway
and
• traction injury to a small tethering vessel
• Management of the Bronchus
• First dissection of the bronchus,
• All peribronchial lymph nodes are swept up bluntly into the specimen
to avoid lymph node contamination of the bronchial margin.
• Minimizing cautery and skeletonization of the airway avoids
devascularization of the bronchial stump, which could lead to
breakdown and bronchopleural fistula.
• After the airway is completely exposed:
• a right-angled, heavy wire stapler is closed over it.
• The anesthesiologist
• inflates the operative lung to confirm no impingement on the remaining
airways.
• Only after adequate ventilation of the remaining lobes:
• has been confi rmed is the stapler fired and the specimen excised.
• the tumor is particularly close to the lobar orifice:
• the airway is sharply cut with a scalpel and
• a bronchoplasty is performed using interrupted 3-0 vicryl suture to ensure a
negative margin.
• Frozen section evaluation of :
• the bronchial margin or
• any close parenchymal margin must be performed routinely.
• Options to cover the bronchial stump : depending on availability and
quality
• a pleural flap,
• azygous vein,
• pedicled pericardial flap, or
• pericardial fat pad,.
• Intercostal muscle flaps
• are preferred if chemoradiation preceded surgery.
• The stump
• is tested by inflation to 30 cm of water pressure by the anesthesiologist.
• If an air leakis present, it is oversewn with interrupted Vicryl suture.
Management of the Fissure
• MOBILIZATION OF THE LOBE

• The pleural cavity is entered through

• the fifth intercostal space for upper lobectomy or any central lesion.

• the sixth space is acceptable for peripheral lower lobe tumors.

• If adhesive pleuritis is anticipated,

• entrance through the bed of the resected fifth rib :
• allows for more expeditious mobilization of the lung, either in the intrapleural or extrapleural plane.
• Sub lobar resection with sampling of N1 and N2 lymph node station.

• Segmentectomy preferred over wedge resection

• Indication Patients with

• poor pulmonary reserve

• Other major comorbidity that contraindicates lobectomy

• ≤2 cm A peripheral tumors (without endobronchial extension and within anatomic segmental boundaries)

• pure adenocarcinoma in situ histology,

• ≥50% ground glass appearance on CT or

• doubling time ≥400 days confirmed on radiologic surveillance

• Surgical margins of at least 2 cm or ≥ the size of the nodule

Segmentectomy
• prior to segmentectomy
• Bronchoscopy evaluation
• is necessary to ensure that the segmental bronchi are disease-free.
• The presence of extrinsic compression,inflammatory changes, and tumors requires more
extensive procedures.
• intraoperative
• assessment of mediastinal and lobar lymph nodes is essential
• If nodes are positive, segmentectomy is unlikely to be curative.
• Tumor size and location are also important considerations
• The right middle lobe
• has minimal preserved lung and therefore does not undergo segmentectomy.
Segmentectomy con….
• Incision
• the approach of choice is a posterolateral thoracotomy via the fifth
intercostal space.
• a muscle incision via the fourth intercostal space is an alternative.
Segmentectomy con….
• Operative technique
• the segmental arterial branches
• are divided first to expose the segmental bronchus.
• The lobar and segmental bronchi are dissected and lobar node dissection is
completed to test for metastases.
• The segmental bronchus
• is then divided and closed with absorbable suture. The bronchus may also be stapled.
Segmentectomy con….
• The veins
• are typically the last vascular structures divided.
• The intersegmental veins delineate the intersegmental plane.
• The surgeon should
• identify, dissect, and divide the appropriate veins,
• taking care to spare the intersegmental vein to allow for venous drainage of other
segments and thus reduce postoperative complications.
Segmentectomy con….
• With the lung inflated

• the parenchyma of the lung is divided.

• The visceral pleura

• is then divided and the segment removed by stapling along the intersegmental plane, ensuring
appropriate margins of about 2 cm.

• Potential air leaks

• should be assessed and repaired and

• chest tubes placed (one in the apex to evacuate air and a basal tube placed posteriorly for drainage ).
Wedge resections
• Anatomic Segmentectomy
• is preferred over wedge resection because
• intrasegmental lymph node resection provides better margins and
• the removal of lymph nodes with segmental bronchi provides better staging.
• Incision
• The approach of choice is a posterolateral thoracotomy via the fifth
intercostal space
• a muscle incision via the fourth intercostal space is an alternative
• Operative technique
• Identified the nodule to be resected
• a wedge resection can be performed by clamping and cutting out the nodule
with margins and
• then sewing with running suture.
• Alternative methods of resection
• include stapling, electrocautery, and laser photoablation followed by excision,
using a 40- to 50-W free beam or a 10- to 15-W contact tip to excise the tumor.
• To minimize invasiveness, video-assisted thoracoscopy is yet another
method that can be used.
• early-stage NSCLC
• Lobectomy with systematic lymph node sampling or lymphadenectomy
constitutes the standard of care,
• and provides patients with the best chance of cure
• for stage IA NSCLC
• Recurrence rates range
• Local from 20% to 30%
• (locoregonal = 5% to 8%,
• distant = 15% to 20%).
• Overall survival ranges between 70% and 80% at 5 years in most published
series
• Overall survival at 5 years was 54% in the segmentectomy group
versus 60% for lobectomy.
• a high operative risk are not candidates for lobectomy, at which point
their options are less extensive surgery or non-operative management
• High operative risk and medically inoperable patients are candidates
for definitive RT after multidisciplinary discussion has concluded the
morbidity of surgical resection outweighs potential benefit.
• Determination of operability is guided by factors
• advanced age,
• cardiovascular or pulmonary impairment, and
• the burden of competing comorbidities.
• Objective quantification has mainly relied on PFT, specifically the FEV1
and the DLCO.
• PRIMARY RADIATION
• reserved for medically inoperable patients as the only available option for
definitive treatment.
• conventional RT
• increased survival compared to no treatment
• a survival benefit of 5-7 months and no change in 5-year OS. 7
• Stereotactic body radiation therapy (SBRT)
• Improved local control (LC) and OS
• a meta-analysis estimating an improvement in 5-year OS from 19% to 42% when
comparing conventional RT to SBRT.
• LC rates of more than 90% and 3-year OS rates of 55%-60% in stage I patients.
• OPERATIVE PREPARATION
• Cessation of Smoking
• Pharmacotherapy : varenicline
• and
• behavioral therapy
• Dobson Amato et al. found a median 9-month improvement in OS in patients
who quit tobacco after diagnosis
• do not advocate for the delay of surgical procedures in favor of a longer
period of abstinence
• The incorporation of the “five major steps to intervention” (ask, advise, assess,
assist, arrange)

• allows the surgeon to

• document the smoking history,
• introduce smoking cessation and its benefits,
• evaluate the patient’s readiness to quit,
• assist with pharmacotherapy initiation, and arrange follow-up to monitor progress toward
smoking cessation.