SMALL CELL LUNG CANCER

Dr.RAHUL P WAGH2nd year Surgical Oncology Resident

Gujrat Cancer And Research Institute

Types of Lung CancerNon-small cell carcinoma (NSCC)

(87%)◦Adenocarcinoma (38%)◦Squamous cell (20%)◦Large cell (5%)

Small cell carcinoma (13%)

Incidence and Etiology• Although the incidence of small cell lung cancer (SCLC) is

declining, it remains a worldwide public health problem.• Only 2% to 3% of patients are never smokers, its incidence

rates mirror smoking patterns.• The gender gap has narrowed such that currently about half

of the patients diagnosed with SCLC are women

0%

5%

10%

15%

20%

25%

30%

35%

40 50 60 70 80

11%

31%33%

19%

5%

Age Distribution: NCDB 2000-2010 for Small Cell Lung Cancer

Anatomy and Pathology

Lymph Nodes in the Lung

Nodes on cross section

Reading a CT Scan

• Neuroendocrine tumors of the lung encompass: low-grade typical carcinoid, intermediate-grade atypical carcinoid, high-grade large cell neuroendocrine carcinoma(LCNEC), and SCLC.

• When a component of NSCLC, including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, spindle cell carcinoma, and giant cell carcinoma, is present, the term combined SCLC is used with mention of the specific histology of the non–small-cell component. In resected specimens, combined SCLC may occur in up to 28% of cases.10

• To diagnose combined SCLC and large cell carcinoma, the large cell carcinoma component must comprise at least 10% of the overall tumor.

Pathology

• Cancer cells should stain positive for keratin, epithelial membrane antigen and TTF-1

• Since they are neuroendocrine they should also stain for: chromogranin A, neuron specific enolase, NCAM and synaptophysin

• 10% of SCLCs -negative for all neuroendocrine markers.

“special stains”

Genetics &Screening• SCLC has been characterized by frequent

inactivating mutations in the critical tumor suppressor genes TP53 (75% to 90%)18 and RB1 (60% to 90%).

• Screening for SCLC by any method is not recommended.

• As SCLCs were not detected at early stages by either LDCT or CXR in the NLST

Diagnosis

• Symptoms- fatigue was the most common, symptom with decreased physical activity, cough, dyspnea, decreased appetite, weight loss, and pain.

• Hemoptysis was noted in 14% • Superior vena cava obstruction is present at

diagnosis in 10% of patients with SCLC.• Rarely, SCLC presents as a solitary pulmonary

nodule. No more than 2% of SCLC present as a superior sulcus tumor

• All patients should undergo a contrast enhanced CT scan of the chest,a gadolinium-enhanced MRI of the head, and whole-body PET or a bone scan.

CT Small Cell

Usually large mass in the mediastinal lymph nodes and may compress the superior vena cava

Biopsy - confirm the cancer and determine the type

Bronchoscopy CT directed biopsy

PET scan showing a typical small cell cancer with a large mediastinal mass making it hard to even see the heart on the left side

Small Cell Lung Cancer

• Most patients with SCLC have metastases at diagnosis.

• Bone involvement is usually characterized by osteolytic lesions.

• Hepatic and adrenal lesions are typically asymptomatic.

• Brain metastases can be detected in at least 18% of patients at diagnosis which are often asymptomatic.

Paraneoplastic syndromes• Are common in SCLC and differ from those observed

with NSCLC.• SCLC accounts for approximately 75% of the tumors

associated with the SIADH. • Ectopic production of atrial natriuretic factor

contributes to the disorder in sodium homeostasis. The primary treatment for hyponatremia in SCLC patients is chemotherapy aimed at treating the disease.

• Cushing syndrome develops in only 5% of patients with SCLC,patients with Cushing syndrome have a very limited survival

• Hypercalcemia is rare in SCLC.

• Subacute peripheral sensory neuropathy is the most frequent paraneoplastic neurologic disorder seen in those with SCLC.

• Less common is the Lambert-Eaton syndrome, characterized by proximal muscle weakness that improves with continued use hyporeflexia, and dysautonomia

• In contrast to the endocrine syndromes, for which successful treatment of the tumor effectively controls the symptoms, the occurrence and severity of the neurologic symptoms is unrelated to tumor bulk and usually does not resolve with antineoplastic therapy.

Staging

Veterans’ AdministrationLung Study Group (VALSG system)

LIMITED STAGE DISEASE • Disease confined to

ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field.

• Contralateral mediastinal involvement

• Treated with combined modality of treatment

EXTENSIVE STAGE DISEASE• Disease beyond ipsilateral

hemithorax which may include malignant pleural or pericardial effusion or hematogenous metastasis

• The presence of supraclavicular lymphadenopathy commonly is associated with extensive disease

• In clinical practice, it is assumed that an effusion is malignant unless three criteria are met: the fluid is transudative, nonhemorrhagic, and cytologically negative on repeated examinations.

Stages of Lung Cancer

• Stage I – small spot no nodes• Stage II – larger or nodes on the side of

the lung (hilar or N1 nodes)• Stage III – very large tumor or lymph

nodes in the middles of the chest (mediastinum or N2 nodes)• Stage IV – metastases to other organs

• Unilateral iliac crest bone marrow aspiration and biopsy should be performed in limited-stage patients with elevations of serum lactate dehydrogenase (LDH) and evidence of myelophthisis(nucleated red blood cells, leukopenia, or thrombocytopenia) on the peripheral blood smear.

• Effusions too small to permit image-guided sampling should not be considered in staging.

• Osseous abnormalities seen on positron-emission tomography (PET) or bone scan require confirmation with magnetic resonance imaging (MRI), CT scan, or biopsy if they represent the only disease site that makes a patient extensive stage.

Management by StageGeneral Recommendations for Initial Management-• If the patient is a never smoker, the pathologic diagnosis of

SCLC should be reviewed as only 2% to 3% of never smokers develop SCLC.

• All patients should undergo a contrast enhanced CT scan of the chest, a gadolinium-enhanced MRI of the head, and whole-body PET or a bone scan.

• All fit patients (Karnofsky performance status greater than 60% or Eastern Cooperative Oncology Group [ECOG] performance status 0, 1, or 2) should initially receive combination chemotherapy with etoposide plus either cisplatin or carboplatin for four to six cycles.

• Patients with limited-stage disease should receive the chemotherapy concurrently with twice-daily thoracic irradiation beginning with the first, second, or third cycle.

• Patients who achieve a response to chemotherapy should receive prophylactic whole-brain radiotherapy at the conclusion of chemotherapy or chemoradiotherapy.

• Patients who have a Karnofsky performance status of 50% or less or ECOG performance status 3 or 4- no routine recommendation status group, supportive care only and referral to hospice are the best options.

Chemotherapy

• EP (Etoposide and Cisplatin) is now the standard first-line chemotherapy regimen for SCLC.

• Etoposide and carboplatin can be considered an appropriate first-line regimen, particularly in patients who cannot tolerate cisplatin

• four to six cycles of chemotherapy appear to be optimal in the management of limited and extensive SCLC. After the completion of this initial treatment, patients should be monitored closely and then offered further chemotherapy at the time of progression.

• Although hematologic toxicities were higher in those patients that receive carboplatin, nonhematologic toxicities were increased in those that receive cisplatin

Chemotherapy for Small Cell

Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data

JCO May 10, 2012 vol. 30 no. 14 1692-1698

Treatment After Relapse• The strongest predictor of outcome for patients

with relapsed SCLC is the duration of remission.• The term sensitive implies an appropriate

response to initial therapy that is maintained for 3 months or more. have a higher likelihood of response to any additional chemotherapy

• Refractory disease either had no response to initial therapy or progressed within 3 months after completing treatment.

• The only approved agent in relapsed disease is topotecan.

Immunotherapy and Other Targeted Therapies

Radiation• Due to the radioresponsiveness of SCLC, modest

doses of radiation from 45 to 50 Gy have been used.

• The maximum tolerated dose of concurrent thoracic chemoradiation seems to be 45 to 51 Gy with a twice-daily approach and 70 Gy daily.

• The target volume included the primary tumor, bilateral mediastinal nodes, and the ipsilateral hilum, excluding uninvolved supraclavicular nodes.

• Early radiation therapy was defined as beginning before 9 weeks after the initiation of chemotherapy and before the third cycle of chemotherapy.

• Late radiation therapy began 9 weeks or more after the initiation of chemotherapy or after the beginning of the third cycle.

• They reported a small but statistically significant improvement in 2-year survival for patients receiving early radiation therapy.

• Low dose prophylactic cranial irradiation (PCI) reduced the risk of brain mets from 58% to 33% and increased 2y survival from 15% to 21% and another study showed a decreased risk of brain mets from 49% down to 14% and improved 1 year survival from 13% up to 27%

• Brain dose of 24 to 30Gy

Benefits of PCI (prophylactic cranial irradiation) of extensive stage small cell in

lowering the risk of developing brain metastases

Surgery• Surgery is not advisable as a sole treatment modality

in this disease.• In some cases, patients who undergo thoracotomy

for an abnormal pulmonary nodule are unexpectedly diagnosed with SCLC In these cases, a complete surgical resection should be performed and the patient should be referred for adjuvant therapy.

• Based on current recommendations, patients with N0 disease should receive adjuvant chemotherapy, whereas patients with nodal involvement should receive chemotherapy and mediastinal radiation.

• The largest experience examining the role of surgery followed by adjuvant therapy in SCLC was a cooperative group trial conducted by the International Society of Chemotherapy Lung Cancer Study Group.

• Four-year survival rates for completely resected, pathologically staged SCLC patients with N0, N1 (n = 58), and N2 who received postoperative therapy were 60%,36%, and 33%, respectively. Based on these studies, most authorities believe that surgery may have a role as part of a multimodality approach, but only for patients with stage I disease.

• A mediastinoscopy should be performed in all patients who are being considered for resection of known SCLCs.

Survivorship Issues• Since the introduction of EP chemotherapy in

the late 1970s, with median survival improving only by 2 months from 7 to 9 months between 1972 and 1990.

• Patients are at greatest risk of dying from SCLC during the first 24 months after diagnosis. This risk declines between years 2 and 3 and is further reduced beyond year 3.

THANK YOU