D A N I E L K I M , M D S U N Y D O W N S T A T E M E D I C A L C E N T E R
A U G U S T 2 1 , 2 0 1 4
Squamous Cell Lung Cancer
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Case Presentation
73 year old male PMH: COPD, PVD, RA 2005 -BCC of nose 2012 -SCC of right neck enlarged LN
PSH: 2005 -Excision of BCC of nose 2012 –Right neck LN biopsy followed by chemo-radiation Jan 2014 –Bronchoscopy, thoracotomy, RLL lobectomy and biopsies
of hilar LN and diaphragm
Social: Quit tobacco 2012
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Case Presentation
Exam Well-developed and thin Skin exam was unremarkable Chest clear to auscultation; incisions well-healed Abdomen soft and non-tender No cervical, axillary or supraclavicular lymphadenopathy Extremities unremarkable
Laboratory 138
4.5
103 16
1.1 74
23
8.6 4.5
0.4
73
19
31
3.9
6.5 271
45
14
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SUV 6.8
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Pathology
January 2014 5cm SCC Moderately differentiated Extends to visceral pleural surface but margins are negative Focal vascular wall invasion Negative hilar LN (0/1) Stage (T2a, N0, M0) 1b
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Postoperative Course
Uneventful hospital course in January 2014
Discharged on POD #8
No complaints per patient
Surveillance PET-CT performed 6 months later…
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SUV 7.7
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Bronchoscopy with Mediastinoscopy
Bronchoscopy and Mediastinoscopy with lymph node biopsies lymphadenopathy at station 4 and station 7
Patient discharged without complication POD #0
Pathology Region 7 – metastatic SCC Region 4 - negative
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Mediastinoscopy
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Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non–small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial Gail E. Darling, MD,a Mark S. Allen, MD,b Paul A. Decker, MS,b Karla Ballman, PhD,b Richard A. Malthaner, MD,c Richard I. Inculet, MD,c David R. Jones, MD,d Robert J. McKenna, MD,e Rodney J. Landreneau, MD,f Valerie W. Rusch, MD,g and Joe B. Putnam, Jr, MDh
Does mediastinal lymph node dissection improve survival when compared to lymph node sampline for N0 or N1 NSCLC?
Prospective Randomized Controlled Clinical Trial June 1999 to February 2004; 1023 met criteria (63 institutes) Sampling performed in 498 vs dissection in 525 patients At median followup at 6.5 years, 43% of the eligible patients
have died and there is no difference in survival; although not statistically significant (8.1 years vs. 8.5 years; P=0.25)
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Squamous Cell Carcinoma of the Lungs
Epidemiology Clinical Presentation Diagnosis Treatment NCCN guidelines Questions
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Epidemiology
Lung cancer is the leading cancer killer in the United States
30% of all cancer deaths in the United States Diagnosed at an advanced stage of disease Lack of adequate adjuvant therapy
The overall 5-year survival for all patients with lung cancer is 15%
SCC accounts for 30 to 40% of lung cancers
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Figure 19-18? A graphical chart?
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Stage TNM Description Five-Year Survival
I 70–76%
a T1, N0 80–83%
b T2, N0 60–65%
II 30–40%
a T1, N1 32–40%
b T2, N1 28–35%
T3, N0
IIIA 10–30%
T3, N1 30–45%
T1–2, N2 7–30%
T3, N2 0–5%
IIIB <10%
T4, any N <10%
Any T, N3 <10%
IV M1 <5%
Overall 14.5%
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Epidemiology
Survival of patients with lung cancer varies according to several demographic and social factors
Positive survival factors (5-year survival) Female sex (18.3% vs. 13.8%; F:M) Younger age (22.8% vs. 13.7%; <45 years vs. >65 years) White race (16.1% vs. 12.2%; Whites vs. African Americans) When access to advanced medical care is unrestricted ,the
racial difference in survival disappears
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Epidemiology
Cigarette smoking is the primary cause of lung cancer 75% of all lung cancers worldwide in 2007 SCC is rare in non-smokers
Smoking Status Relative Risk for SCC
Current 16
Quit 1-9 years 6
Quit > 10 years 2
Non-smoker 1
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Epidemiology
Other factors to consider: Biology
Chromosome deletions, Tumor suppressor gene mutations, overexpression, protooncogenes
Chemicals
Asbestos and flammable compounds: Air polution, construction, shipyard, truckers, cooks, cosmetologists, miners, etc.
Vitamin A deficiency
Certain diseases [scleroderma] have a defined predisposition for the
development of lung cancer
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Clinical Presentation is Diverse
Central >> Peripheral location Regional spread and Metastatic Disease Paraneoplastic Syndromes
Locations: Right > Left; and Upper > Lower/Middle 7% with Synchronous primary lung cancers 10% develop a metachronous tumor (2%/year risk)
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Central vs. Peripheral Lung Tumors
Central Tumors – 80% Cough Wheezing Stridor Dyspnea Hemoptysis Pain Pneumonia
Peripheral Tumors – 20% Cough Chest wall pain Effusion Abscess Horner Syndrome -ipsilateral miosis, ptosis, anhidrosis Pancoast syndrome -ipsilateral shoulder and arm pain in the C8-T1 nerve root distribution
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Regional and Metastatic Disease
Regional Disease Hoarseness -Recurrent nerve paralysis Dysphagia -Compression of esophagus SVC syndrome -Invasion/compression of SVC Pericardial Tamponade -Invasion of pericardium
Metastatic Disease Constitutional: -Anorexia -Weight loss -Weakness /Malaise Pulmonary and hilar lymph nodes Mediastinal lymph nodes Lung Liver (Jaundice) Bone (25%) Brain (10-25%) Adrenal glands Pancreas Kidney Soft tissues (8%) Myocardium
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Paraneoplastic Syndromes
Hypercalcemia 10% of patients with lung cancer and is most often due to
metastatic disease 15% of cases are caused by secretion of ectopic
parathyroid hormone–related peptide, most often with squamous cell carcinoma
A diagnosis by measurement of elevated serum levels of parathyroid hormone
Symptoms of hypercalcemia include lethargy, depressed level of consciousness, nausea, vomiting, and dehydration
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Paraneoplastic Syndromes
Peripheral and central neuropathies 16% of all Lung cancer patients
SCC causes 25% of these cases
Immune mediated; Cancer cells express antigens of the nervous system
and are targeted by immune cells
CNS metastases must be ruled out with CT or magnetic resonance imaging (MRI) of the head for patients with neurologic or muscular symptoms
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Diagnosis and Treatment
A new solitary pulmonary nodule on CXR 20 - 40% chance of being malignant > 50% chance of malignancy in smokers. A new primary lung cancer is most common in patients with a
history of uterine carcinoma (74%), bladder carcinoma (89%), lung carcinoma (92%), and head and neck carcinoma (94%)
Radiologic factors suggestive of cancer Growth over time Size >3cm Non-calcified Irregular, lobulated, or spiculated edges Solid > partial-solid > non-solid nodules
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Diagnosis and Treatment
Lung cancers have volume-doubling times of 20 to 400 days
Lesions with shorter doubling times are likely due to infection
Longer doubling times suggest benign tumors but can indicate slower-growing lung cancer
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Diagnosis and Treatment
Picture of scc lung ct scan
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Algorithm for Diagnosis and Treatment
History and Physical Smoking history Pulmonary history Cancer history Environmental or occupational exposure Infectious exposure Examination of head/neck/oropharynx
CXR CT Chest Laboratory
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Algorithm for Diagnosis and Treatment
Incidental Solitary Pulmonary Nodule
<8mm – observe with 6-month CT chest
>8mm solid and non-calcified – obtain PET-CT Low suspicion: 3-month CT Higher suspicion: Biopsy / Excision
>10mm part solid and non solid – observe with 3-6 month CT
If stable; consider repeat CT or biopsy/excision If growing; proceed with bronchoscopy and excision
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Algorithm for Diagnosis and Treatment
Objectives Evaluate tissue Evaluate for metastatic disease Assess suitability of patient for resection and lung volume
reduction surgery
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Algorithm for Diagnosis and Treatment
NSCLC (Non-Small Cell Lung Cancer) or highly suspicious nodule Bronchoscopy for proximal lesions VATs preferred over FNA for peripheral lesions
Fewer complications and lower false negative rate
Preoperative assessment for lung reduction surgery PFTs Cardiac workup if necessary
Clinical Staging CT chest/abdomen/pelvis MRI brain PET-CT Mediastinal lymph node evaluation
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Contraindications to Pulmonary Resection
Absolute Relative
Myocardial infarction within previous 3 months
Myocardial infarction within previous 6 months
SVC syndrome (due to metastatic tumor) SVC syndrome (due to primary tumor) Bilateral endobronchial tumor Recurrent laryngeal nerve paralysis (due to
primary tumor in aorticopulmonary window)
Contralateral lymph node metastases (N3) Horner syndrome Malignant pleural effusion Small cell histology Distant metastases (except solitary brain and adrenal metastases)
Metastases higher than the midtracheal lymph nodes
Pericardial involvement FEV1 < 0.8 L (< 50%) FEV1 0.9–2.4 and insufficient pulmonary reserve for planned resection
Main pulmonary artery involvement
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Algorithm for Diagnosis and Treatment
Stage Ia, Ib, Exploration, resection with bronchoscopy, mediastinoscopy
and lymph node biopsies Adjuvant chemotherapy for high-risk biology (poorly
differentiated) or incomplete sampling of nodes R0 resections are considered for chemotherapy R1-2 resections receive re-resection and RT +/- chemo
Stage IIa, IIb Same as Stage Ia-b R0 resections receive chemotherapy R1-2 resections receive re-resection and chemo-RT
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Algorithm for Diagnosis and Treatment
Lobectomy (mortality 2.9%) is the standard of care for resection. Include a 1-cm margin of normal proximal bronchus
Frozen section: Interlobar (hilar) lymph nodes Pneumonectomy (mortality 6.2%) is required for
proximal lesions involving the main stem bronchus or the interlobar (hilar) lymph nodes
Complications: cardiac arrhythmias, hemorrhage, infection (empyema), bronchopleural fistula, respiratory insufficiency, and pulmonary embolism
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Algorithm for Diagnosis and Treatment
Stage IIIa and IIIb Preoperative workup should include MRI spine and thoracic
inlet for lesions Resectable tumors with bronchoscopy receive Chemo+/-RT
postoperatively Consideration for induction Chemotherapy Unresectable tumors receive Chemo-RT R1-2 resections receive Chemo-RT
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Stage IV Disease The treatment of patients with stage IV disease is
chemotherapy and radiation Very limited resections may be performed for metastatic
disease (solitary nodules to the brain, adrenals, etc.) Growing use of radiation therapy and chemotherapy
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Chemotherapy
Study CT Regimen Radiation Therapy 5-year Survival CT vs. Control
Italian Stage IB Study Cis/Etoposide × 6 No 63% vs. 45%
IALT LeChevalier Various platinum Yes ± 44.5% vs. 40.4%
CALGB 9633 Strauss Carbo/Taxol × 4 No 69% vs. 54%
JBR.10 Alam Vin/P × 4 No 71% vs. 59%2
Table 18–11. Adjuvant Trials Favoring Use of Chemotherapy in Completely Resected Non–Small Cell Lung Cancer.1 1CT, Carbo/Taxol, carboplatin paclitaxel; Vin/P, vinorelbine cisplatin; Cis, cisplatin. 24-year survival statistics.
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Test Questions
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Question 1/4
A 59-year-old man who underwent removal of a malignant tumor 2 years earlier has a solitary lung nodule 1.5 cm in diameter. For this patient to be considered an operative candidate, which of the following criteria must be met?
A. The tumor doubling time must be longer than 40 days. B. Even if effective systemic therapy is available, resection of metastatic lesions is preferred.
C. Recurrence at the primary site must be managed before therapy for metastatic disease is begun.
D. If pulmonary reserve is marginal, resection of the maximal number of metastatic foci should be performed.
E. It must be possible to control extrathoracic metastasis with another modality, such as radiation therapy or reexcision.
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Question 1/4
A 59-year-old man who underwent removal of a malignant tumor 2 years earlier has a solitary lung nodule 1.5 cm in diameter. For this patient to be considered an operative candidate, which of the following criteria must be met?
A. The tumor doubling time must be longer than 40 days. B. Even if effective systemic therapy is available, resection of metastatic lesions is preferred.
C. Recurrence at the primary site must be managed before therapy for metastatic disease is begun…Correct!
D. If pulmonary reserve is marginal, resection of the maximal number of metastatic foci should be performed.
E. It must be possible to control extrathoracic metastasis with another modality, such as radiation therapy or reexcision.
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Question 2/4
A 4-cm peripheral squamous cell carcinoma of the lung of a 60-year-old man with a pleural effusion positive for malignant cells would be classified by the tumor, node, metastasis (TNM) system as: A) T3N0M1b B) T1aN0M1a C) T2aN0M1a D) T3N0M0 E) T4N0M1a.
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Question 2/4
A 4-cm peripheral squamous cell carcinoma of the lung of a 60-year-old man with a pleural effusion positive for malignant cells would be classified by the tumor, node, metastasis (TNM) system as: A) T3N0M1b B) T1aN0M1a C) T2aN0M1a…..Correct! D) T3N0M0 E) T4N0M1a.
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Question 3/4
A 42-year-old man has a solitary "coin lesion" 2 cm in diameter in the area of the right upper lobe on a routine chest radiograph. Which of the following statements is true?
A. Calcification in a concentric or "popcorn" configuration denotes a malignant lesion B. A radiograph from 5 years earlier shows the lesion to be 1.2 cm in diameter and suggests malignant growth C. In the absence of previous radiographs, the lesion should be followed by serial radiographs every 6 months D. Needle aspiration that yields "chronic inflammatory cells" denotes a benign lesion E. If computed tomography shows mediastinal adenopathy, mediastinoscopy is preferable to thoracotomy.
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Question 3/4
A 42-year-old man has a solitary "coin lesion" 2 cm in diameter in the area of the right upper lobe on a routine chest radiograph. Which of the following statements is true?
A. Calcification in a concentric or "popcorn" configuration denotes a malignant lesion B. A radiograph from 5 years earlier shows the lesion to be 1.2 cm in diameter and suggests malignant growth C. In the absence of previous radiographs, the lesion should be followed by serial radiographs every 6 months D. Needle aspiration that yields "chronic inflammatory cells" denotes a benign lesion E. If computed tomography shows mediastinal adenopathy, mediastinoscopy is preferable to thoracotomy…Correct
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Question 4/4
A 55-year-old man who is a long-term smoker has a 2-cm, irregular, noncalcific lesion in the right upper peripheral lung on a routine chest x-ray. The only abnormality seen on computed tomographic (CT) scan is the peripheral nodule. He is asymptomatic except for nightly low-grade fevers. Bronchoscopy is negative. Management should include:
A. skin tests for tuberculosis and fungi B. excision of the lesion C. Mediastinoscopy D. trial of antibiotic therapy E. careful observation with serial chest x-rays
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Question 4/4
A 55-year-old man who is a long-term smoker has a 2-cm, irregular, noncalcific lesion in the right upper peripheral lung on a routine chest x-ray. The only abnormality seen on computed tomographic (CT) scan is the peripheral nodule. He is asymptomatic except for nightly low-grade fevers. Bronchoscopy is negative. Management should include:
A. skin tests for tuberculosis and fungi B. excision of the lesion…Correct! C. Mediastinoscopy D. trial of antibiotic therapy E. careful observation with serial chest x-rays
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