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Small Cell Lung Cancer Treatment & Management

  • Author: Winston W Tan, MD, FACP; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
 
Updated: Oct 06, 2015
 

Approach Considerations

Small cell lung cancer (SCLC) is characterized by rapid growth and early dissemination. For the approximately 30% of patients with SCLC who have limited-stage disease at the time of diagnosis (ie, tumors confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes), management typically involves combination platinum-based chemotherapy and thoracic radiation therapy given with curative intent. Patients who achieve a complete or partial response should be offered prophylactic cranial irradiation (PCI).[13]

Extensive-stage SCLC (ie, SCLC that has spread beyond the supraclavicular areas, or with distant metastases) remains incurable with current management options, and patients are treated with combination chemotherapy. Several chemotherapy combinations are active in SCLC, but usually a platinum-containing regimen is chosen. However, despite strides in the management of SCLC, there has been little change in survival over the past 2 decades for limited- or extensive-stage disease.[34, 35] Indeed, very few new agents with activity in SCLC have been identified, even as identification of molecular targets and targeted therapies has proceeded at a brisk pace in non-SCLC.

The American College of Chest Physicians (ACCP) and the National Comprehensive Cancer Network (NCCN) guidelines recommend following treatment recommendations for SCLC in patients who have mixed histologic features of SCLC and non–SCLC.[25, 29]

Elderly patients with SCLC who have a good performance status (PS) (ie, Eastern Cooperative Oncology Group [ECOG] PS 0 or 1) and intact organ function should receive standard carboplatin-based chemotherapy. However, even those who have poor prognostic factors (eg, poor PS, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in PS.[29]

Unlike non-SCLC, SCLC has not been shown to respond well to targeted therapies.[29] Studies of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors have yielded disappointing results: bevacizumab, aflibercept, and vandetanib have failed to demonstrate significant improvements in survival.[36] However, a recent phase II trial of sunitinib maintenance therapy in patients with untreated extensive-stage SCLC reported a modest but significant improvement in median progression-free survival, from 2.1 months with placebo to 3.7 months with sunitinib.[37]

See Small Cell Lung Cancer Treatment Protocols for summarized information.

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Combination Chemotherapy

A number of randomized trials have tried to answer questions concerning the superiority of combination over single-agent chemotherapy, the number of drugs to be used in combination, and dose intensity. Nonrandomized trials of combination chemotherapy have shown superior response rates and survival compared with single-agent chemotherapy. Common combinations include cisplatin/etoposide (PE), cisplatin/irinotecan (IP), carboplatin/etoposide, and carboplatin/irinotecan.

Several platinum-based and non–platinum-based chemotherapy regimens have been used in the treatment of small cell lung cancer (SCLC) with varying results.

In a systematic review that compared the effectiveness of these regimens, Amarasena et al concluded that platinum-based chemotherapy regimens did not provide a statistically significant benefit over non–platinum-based agents in survival or overall tumor response. However, platinum-based agents did result in higher complete response rates, albeit with an associated higher incidence of nausea, vomiting, anemia, and thrombocytopenia. The investigators suggested that non–platinum-based chemotherapy regimens may have a better risk-benefit profile.[38]

Cisplatin and etoposide

PE is currently the most widely used regimen in both limited- and extensive-stage SCLC. The combination of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV) has been compared with PE in at least 2 randomized trials of previously untreated extensive-stage SCLC and showed similar survival outcomes. The PE combination is associated with less myelosuppression, whereas CAV has the convenience of administration in a single day (PE requires a 3-day program).[39]

Cisplatin and irinotecan

The PE combination has also been compared with other platinum-based regimens (eg, IP) and has been found to be effective for metastatic SCLC. A large Japanese study that compared PE with IP in patients with extensive-stage disease showed a 3-month-longer survival period with the IP combination (12.8 mo) relative to the PE combination (9.4 mo).[40]

Nonetheless, a more recent meta-analysis of 12 randomized, controlled trials found that, although the IP regimen significantly reduced mortality risk compared with the PE regimen, it also produced more hematologic toxicities in patients with extensive-stage SCLC.[41] In addition, the overall response rate between PE and IP treatment groups did not differ.[41] One of the trials in this meta-analysis suggested overall survival may be prolonged with a PCDE (etoposide, cisplatin, epirubicin, cyclophosphamide) regimen.

Several subsequent trials comparing the same combinations did not show a survival advantage with the IP combination, including a US trial that demonstrated an overall median survival time of 9.3 months for those in the IP group versus 10.2 months for those in the PE group.[42] Therefore, the PE combination remains the first-line combination chemotherapy choice for most physicians.

Carboplatin and etoposide versus carboplatin and irinotecan

The combination of carboplatin and etoposide has been used in patients with compromised renal function. A study by Schmittel et al found that the combination of carboplatin/irinotecan was not superior to that of carboplatin/etoposide.[43]

Cisplatin-based versus carboplatin-based chemotherapy

A systematic review of randomized trials comparing cisplatin- to carboplatin-based chemotherapy as the first-line treatment for SCLC found no significant difference in efficacy between the 2 treatments.[44] This meta-analysis included 4 trials with a total of 663 patients (328 treated with cisplatin; 335 treated with carboplatin).

In the study, median overall survival was 9.6 months among cisplatin-treated patients and 9.4 months among carboplatin-treated patients. Median progression-free survival was 5.5 months among cisplatin-treated patients and 5.3 months among carboplatin-treated patients. The objective response rate was 67.1% and 66.0%, respectively.[44] However, hematologic toxicity was higher with carboplatin, whereas nonhematologic toxicity was higher with cisplatin.[44]

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Chemotherapy Dose Intensity and Density

Patients with extensive-stage small cell lung cancer (SCLC) should receive 4-6 cycles (but not >6 cycles) of cisplatin- or carboplatin-based combination chemotherapy (eg, cisplatin plus etoposide or irinotecan).[25, 29, 15] Several trials have tested the use of higher doses of standard chemotherapeutic regimens in previously untreated SCLC. Despite early enthusiasm brought on by higher initial response rates, most of these trials have failed to demonstrate improved survival.[45]

A trial by Arriagada et al comparing standard and higher doses of cyclophosphamide and cisplatin in the first cycle of chemotherapy yielded a superior survival rate only in patients receiving higher-dose chemotherapy.[46] Higher-dose regimens, however, may cause life-threatening myelosuppression and, in the absence of survival advantage, should not be used outside of a clinical trial.

Another approach to increase the intensity of chemotherapy is to shorten the interval between cycles (increased dose density). Again, although phase II trials suggested the superiority of such an approach, randomized trials failed to show an advantage to the use of intensive weekly chemotherapy over standard regimens. One of the problems has been myelosuppression with weekly programs, such that the planned dose intensity has not been reached. Growth factor support may overcome this, but until randomized trials are reported to show clear superiority of such an approach, it remains investigational.

High-dose chemotherapy with bone marrow or stem cell transplantation

The available data do not support the use of high-dose chemotherapy with bone marrow or stem cell transplantation, because no randomized trials have evaluated this approach to assess whether it will produce better survival rates than standard management and whether it is associated with greater immediate and delayed toxicity.

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Limited-Stage SCLC - Standard Management

Standard management of patients with limited-stage small cell lung cancer (SCLC) involves combination chemotherapy and concurrent thoracic radiotherapy.Therefore, it is necessary to refer patients to a radiation oncologist, as well as a medical oncologist. For combination chemotherapy, the American College of Chest Physicians (ACCP) recommends four cycles of a platinum agent and etoposide.[29]

For patients receiving chemotherapy and radiotherapy, National Comprehensive Cancer Network guidelines recommend a maximum of four to six cycles of cisplatin and etoposide.[25] Continuing chemotherapy beyond four to six cycles has not been shown to significantly improve overall survival in most randomized controlled trials, and has been associated with considerable risk of increased toxicity; indeed, many oncologists now stop after four cycles of therapy.[25, 29, 15]

Patients who experience a complete or partial response to initial therapy and those who have undergone resection followed by adjuvant chemotherapy should be offered prophylactic cranial irradiation (PCI).

Radiotherapy

Patients with limited-stage SCLC typically receive concurrent chemotherapy and thoracic radiotherapy, which should begin as early as possible, preferably within 30 days of the start of chemotherapy.[29, 15] For patients who are eligible for early concurrent chemoradiotherapy, the American College of Chest Physicians (ACCP) recommends concurrent accelerated hyperfractionated radiotherapy (twice-daily treatment) with platinum-based chemotherapy.[29]

In a randomized trial by Takada and colleagues in which treatment using cisplatin plus etoposide (PE) with concurrent thoracic radiotherapy was compared with treatment using PE with sequential thoracic radiotherapy, the investigators reported superior 2- and 5-year survival rates (2-y survival, 35.1% vs 54.4%, respectively; 5-y survival, 18.3% vs 23.7%, respectively) with the concurrent approach.[47] However, hematologic toxicity was greater in the concurrent arm.

In another randomized trial, Turrisi and colleagues demonstrated superiority of concurrent hyperfractionated radiotherapy administered with 4 cycles of PE in limited-stage SCLC relative to once-daily radiotherapy and concurrent PE.[48] The 10% survival improvement reported in this trial is the largest survival improvement ever noted in SCLC. In addition, 5-year survival rates were 26% versus 16%, respectively, in favor of hyperfractionated radiotherapy.[48] However, a major flaw in this trial was that the biologic equivalent dose of radiotherapy was not equivalent between the 2 treatment arms.

The European Society for Medical Oncology (ESMO) notes that twice-daily radiotherapy is inconvenient and is associated with a significantly elevated rate of transient grade 3 esophagitis.Nevertheless,[15]

Prophylactic cranial irradiation

The ACCP and the 2013 National Comprehensive Cancer Network (NCCN) guidelines recommend PCI in patients with limited-stage disease who have achieved a complete remission or in those with stage I disease who have undergone resection.[25]

The use of PCI was initially considered controversial.[49] Several randomized trials showed a decrease in central nervous system (CNS) relapse rate with PCI but no survival advantage. Additionally, patients receiving PCI had a higher incidence of neuropsychiatric dysfunction than did those who did not receive PCI.[49]

Arriagada et al performed a meta-analysis of randomized trials of PCI in limited-stage SCLC and showed a 5% overall survival advantage in patients who received PCI.[46] Although such an analysis has inherent limitations, PCI is currently offered to patients with limited-stage SCLC who have achieved a complete or partial response after having completed initial chemoradiotherapy.

In a pooled analysis that evaluated outcomes of PCI in 739 SCLC patients with stable disease or better after treatment with chemotherapy with or without thoracic radiation therapy, Schild et al found that PCI resulted in a significant survival benefit in patients with either limited or extensive SCLC.[18] Dose fractionation appeared to be important, and PCI was associated with an increase in specific and overall grade 3+ adverse events.[50]

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Extensive-Stage SCLC - Standard Management

Patients with extensive-stage small cell lung cancer (SCLC) are treated with combination chemotherapy alone. The administration of carboplatin or cisplatin plus etoposide remains the standard of care in North America for extensive SCLC.

The American College of Chest Physicians (ACCP), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) guidelines recommend that patients with extensive-stage disease receive 4-6 cycles (but not >6 cycles) of cisplatin- or carboplatin-based combination chemotherapy (eg, cisplatin plus etoposide or irinotecan).[25, 29, 15]

Although cisplatin/etoposide (PE) remains the most widely used combination, a randomized trial that compared the combination of cisplatin with either etoposide or irinotecan in extensive-stage disease demonstrated that the combination of cisplatin and irinotecan (IP) was superior to that of PE. The median survival was 12.8 months with IP, versus 9.4 months with the PE combination. The 2-year survival rate was also superior at 19.5% for IP, versus 5.2% for PE.[40]

However, a confirmatory study in the United States failed to show the superiority of either regimen.[42]

Possible reasons for these contrasting results may have to do with differences in doses and schedules of the chemotherapeutic agents, as well as with genetic changes within different study populations. Although PE and IP had comparable overall response rates and survival outcomes, the IP combination had more gastrointestinal (GI) toxicity.[51]

A German clinical trial reported that topotecan/cisplatin had a similar overall response rate to PE in extensive SCLC but a better time to progression and objective response rate than did PE.[52]

Radiotherapy

In general, radiotherapy is used only to palliate symptoms, if required (eg, for painful bone metastases) in extensive-stage SCLC. Response rates are excellent, but patients invariably relapse. The ACCP indicates that consolidative thoracic radiotherapy to the chest is a treatment option for patients who achieve a complete response (CR) outside the chest and complete or partial (PR) response in the chest.[29]

In a phase III randomized controlled trial, Slotman et al showed that patients with extensive-stage SCLC who had responded to chemotherapy may benefit from thoracic radiotherapy (30 Gy in 10 fractions). Although overall survival at 1 year was not significantly different in the patients who received thoracic radiotherapy, 2-year overall survival was 13% with radiotherapy versus 3% without (P=0.004). At 6 months, progression-free survival was 24% with radiotherapy versus 7% without (P=0.001). No severe toxic effects from radiotherapy were noted.[53]

Prophylactic cranial irradiation

As with limited-stage disease, offer prophylactic cranial irradiation (PCI) to all responding patients with extensive stage SCLC[25, 29, 15] ; this treatment should be considered standard therapy for this stage of the disease in these patients. Brain metastases at the time of initial diagnosis in extensive SCLC are present in about 18% of patients and increase to about 80% at 2 years.

A study by the European Organization for Research and Treatment of Cancer (EORTC) that randomized patients responding to systemic chemotherapy into 2 groups, those who received PCI and those who did not, found that the 1-year survival rate for the PCI-treated group was 27.1%, compared with 13.3% for patients who did not receive PCI.[49]

In the study, PCI not only reduced the incidence of brain metastases but also improved disease-free and overall survival rates.

However, the 2010 European Society for Medical Oncology (ESMO) practice guidelines noted that safety data on PCI administered concurrently with chemotherapy are lacking; therefore, this combination is not recommended outside of a clinical trial.[15]

Gamma knife stereotactic radiosurgery

Gamma knife stereotactic radiosurgery is a salvage option for patients with brain metastases for whom previous whole-brain irradiation has failed.[54]

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Management of Relapsed SCLC

Patients with relapsed small cell lung cancer (SCLC) have an extremely poor prognosis. Individuals whose disease does not respond to or that progresses on initial treatment (ie, patients with refractory disease) or those whose SCLC relapses within 6 months of completion of therapy have little chance of responding to additional chemotherapy.

In general, the administration of cisplatin and etoposide (PE) after vincristine (CAV) failure produces better response rates than does CAV given after PE.

Topotecan received US Food and Drug Administration (FDA) approval in 2007 for use in chemotherapy-sensitive disease after failure of front-line chemotherapy.[55] Because of the lack of long-term benefit of this therapy, however, patients with relapsed or refractory SCLC should be encouraged to enroll in clinical trials, if their condition permits.[56]

The American College of Chest Physicians (ACCP) recommends offering second-line, single-agent chemotherapy to patients with relapsed or refractory SLCL. For patients who relapse more than 6 months after completion of initial chemotherapy, the ACCP recommends reusing the previously administered first-line chemotherapy regimen. Enrollment in a clinical trial is encouraged.[29]

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Management of Brain Metastases and Spinal Cord Compression

Brain metastases

Management of symptomatic brain metastases includes high-dose corticosteroids (eg, intravenous [IV] dexamethasone 10 mg initially, followed by an IV or oral [PO] dose of 4-6 mg q6h) and immediate whole brain radiation therapy.

For patients with asymptomatic brain metastases, systemic chemotherapy may be initiated, with plans for close surveillance of the central nervous system (CNS) metastases and initiation of brain radiation after completion of systemic treatment.

In patients with small cell lung cancer (SCLC), brain metastases usually respond to systemic chemotherapy, but radiation can be sandwiched between cycles of chemotherapy if there is any clinical or radiographic evidence of progression of CNS disease.

Spinal cord compression

Spinal cord compression is an oncologic emergency, because patients rarely regain neurologic function once it has been lost. New onset of back pain in patients known to have malignant disease should raise the suspicion of cord compression.

A thorough neurologic examination and radiologic evaluation of the spine are indicated with any suspicion of spinal cord compression. The goal is to prevent the development of neurologic deficit, since such a deficit, once present, can progress within hours to cause complete paraplegia. Any delay in instituting appropriate therapy may result in permanent neurologic deficit.

Patients in whom spinal cord compression is suspected should receive IV corticosteroids even before being sent for magnetic resonance imaging (MRI). The typical dose is 10 mg of dexamethasone IV, followed by 4-6 mg IV/PO every 6 hours.

If spinal cord compression occurs in a patient with known SCLC, definitive management consists of radiation therapy and/or neurosurgical decompression, which should be undertaken without delay.

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Surgical Resection

Historically, patients undergoing surgery for small cell lung cancer (SCLC) had a dismal prognosis. However, more recent data suggest that patients with true stage I SCLC may benefit from surgical resection. The American College of Chest physicians (ACCP) recommends that patients being considered for resection undergo invasive mediastinal staging and extrathoracic imaging, such as cranial computed tomography (CT) scanning or magnetic resonance imaging (MRI), abdominal CT scanning, and bone scanning.[29]

Fewer than 5% of patients with SCLC present with such early stage disease, but those who are found to have clinical stage T1/T2 N0 disease after initial staging work-up should undergo invasive mediastinal lymph node evaluation via mediastinoscopy, mediastinotomy, or endobronchial ultrasound-guided biopsy.[57, 15] If there is no evidence of mediastinal lymph node involvement, then surgical exploration with resection of the primary tumor and mediastinal lymph node sampling is a reasonable treatment option.

Due to the systemic nature of SCLC, all patients should receive adjuvant platinum-based chemotherapy and prophylactic cranial irradiation (PCI) after successful resection.[29]

In a review by Anraku and Waddel, the investigators indicated that surgical resection combined with chemotherapy for T1-2, N0, M0 SCLC may offer better local control of the disease than does chemotherapy alone.[58] In addition, curative resection following induction chemoradiotherapy has shown a control of local relapse in almost 100% of patients. Likewise, 5- and 10-year survival rates were 39% and 35%, respectively, for all included patients, resected or not, and they were 44% and 41%, respectively, for patients with stage IIB to IIIA disease treated with a trimodality approach that included adjuvant surgery.[58]

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Management of Complications

Physicians should be aware of potential complications in patients with small cell lung cancer (SCLC), including tumor lysis syndrome and electrolyte abnormalities.

Tumor lysis syndrome

Tumor lysis can occur rapidly in patients with SCLC on institution of chemotherapy, especially in cases of extensive-stage disease. The laboratory features of tumor lysis syndrome are hyperuricemia, hyperphosphatemia, hypocalcemia, and hyperkalemia. Patients should be well hydrated and, preferably, premedicated with allopurinol. The management of established tumor lysis syndrome is urinary alkalinization, correction of electrolyte abnormalities, and dialysis, if necessary.

Electrolyte abnormalities

SCLC is associated with a number of electrolyte abnormalities because of frequent production of peptide hormones. The most common abnormality is hyponatremia, which, if severe, may cause neurologic symptoms and signs, including seizures, coma, and death. Prompt recognition of hyponatremia and its severity is important.

Evidence that supports the prognostic value of this abnormality was shown in a retrospective study of 395 SCLC patients with limited and extensive disease in which patients with hyponatremia had a significantly shorter median survival time than did patients without hyponatremia.[59]

Hyponatremia results from inappropriate secretion of antidiuretic hormone (ADH), which results in the inability of the kidneys to excrete free water. Syndrome of inappropriate ADH (SIADH) is reported in 5-10% of patients with SCLC. The serum sodium level is usually less than 130 mEq/L. Other causes of hyponatremia (ie, volume depletion, abnormal renal function) must be excluded.

Fluid restriction and pharmacologic therapy in the form of demeclocycline (a tetracycline antibiotic that decreases the sensitivity of renal tubules to the action of ADH) are the usual forms of management.

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Consultations

Patients in whom lung cancer is suspected may require consultation with a pulmonologist to establish a diagnosis. Once a diagnosis has been made, medical and radiation oncologists should be consulted to complete the staging workup and devise a management plan. In addition, owing to the importance of weight loss as an indicator of poor prognosis in persons with small cell lung cancer (SCLC), obtain a dietary consultation for patients with persistent weight loss.

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Long-Term Monitoring

Patients with small cell lung cancer (SCLC) require close monitoring for adverse effects and response to therapy. Blood work, including a complete blood count (CBC) with differential, is needed before each cycle of chemotherapy to ensure marrow recovery before the next dose of chemotherapy is administered. Renal function should be monitored because of nephrotoxicity from cisplatin.

Serum lactate dehydrogenase (LDH), if elevated before the start of therapy, is a good marker for response and should be monitored. In addition, computed tomography (CT) scans should be obtained after 2 cycles of therapy to assess response before chemotherapy is continued. In general, patients who are asymptomatic require follow-up only as clinically needed.[15]

Patients who smoke cigarettes should be encouraged to quit. A meta-analysis by Parsons et al suggested that smoking cessation after diagnosis of early stage lung cancer may improve prognosis, probably by reducing cancer progression. Evaluation of data from 9 studies showed that the estimated 5-year survival rate in limited-stage SCLC was 63% in patients who quit smoking, versus 29% in those who continued to smoke.[6]

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Contributor Information and Disclosures
Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, Texas Medical Association, American Society of Clinical Oncology, Philippine Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Irfan Maghfoor, MD Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Acknowledgements

Michael Perry, MD, MS, MACP† Former Nellie B Smith Chair of Oncology Emeritus, Former Director, Division of Hematology and Medical Oncology, Former Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

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High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the image.
This coronal positron emission tomogram shows a large, focal, hypermetabolic area on the right that is consistent with a large mass in the central portion of the right upper pulmonary lobe. Multiple other smaller hypermetabolic areas suggest lymph-node metastatic disease in the chest, abdomen, and right supraclavicular region.
Table 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC
Organ System Syndrome Mechanism Frequency
Endocrine SIADH Antidiuretic hormone 15%[20]
Ectopic secretion of ACTH ACTH 2-5%[21]
     
Neurologic Eaton-Lambert reverse myasthenic syndrome   3%[22]
Subacute cerebellar degeneration    
Subacute sensory neuropathy    
Limbic encephalopathy Anti-Hu, anti-Yo antibodies  
ACTH = adrenocorticotropic hormone; SCLC = small cell lung cancer; SIADH = syndrome of inappropriate antidiuretic hormone.



Sources:  (1) Campling BG, Sarda IR, Baer KA, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. May 15, 1995;75(10):2442-51[20] ; (2) Shepherd FA, Laskey J, Evans WK, et al. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. Jan 1992;10(1):21-7[21] ; (3) Sher E, Gotti C, Canal N, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. Sep 16, 1989;2(8664):640-3.[22]



Table 2. AJCC TNM Categories for Lung Cancer
Primary Tumor (T) Tumor Size Location of Involvement
TX Primary tumor can’t be assessed, or sputum cytology reveals tumor cells but the tumor is not seen on radiologic or bronchoscopic evaluation
T0 No evidence of a primary tumor
Tis Carcinoma in situ
T1 ≤3 cm in diameter Surrounded by lung or visceral pleura; no invasion more proximal than lobar bronchus
T2
  • >3 cm but ≤7 cm diameter, or
  • (see right column)
  • Main bronchus, ≥2 cm distal to carina, or
  • Visceral pleura, or
  • Hilar region, but not entire lung, associated with atelectasis/obstructive pneumonitis
T2a >3 cm but ≤5 cm diameter  
T2b >5 cm but ≤7 cm diameter  
T3
  • >7 cm diameter, or
  • (see right column)
Direct invasion of:
  • Parietal pleural chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or
  • Main bronchus < 2 cm distal to carina (but not carina itself), or
  • Entire lung with associated atelectasis/obstructive pneumonitis, or
  • Same lobe, separate tumor nodule(s)
T4 Any size Invasion of:
  • Mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina
  • Different ipsilateral lobe, separate tumor nodule(s)
Node (N) Location of Regional Metastatic Involvement
NX Regional lymph nodes can’t be assessed
N0 No regional lymph node metastasis
N1
  • Ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and
  • Intrapulmonary nodes, including direct extension
N2 Ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Contralateral mediastinal, contralateral hilar, ipsilateral/contralateral scalene, or supraclavicular lymph node(s)
Metastasis (M) Location of Distant Metastatic Involvement
M0 No distant metastasis
M1 Distant metastasis
  M1a
  • Contralateral lobe tumor with separate tumor nodule(s), or
  • Malignant pleural effusion, or
  • Malignant pericardial effusion
  M1b Distant metastasis
AJCC = American Joint Committee on Cancer.



Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:299-330[26] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2013;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 5, 2011.[25]



Table 3. AJCC Stage Groupings for Lung Cancer
  Primary Tumor (T) Regional Node (N) Metastasis (M)
Occult Cancer TX N0 M0
Stage 0 Tis N0 M0
Stage I A T1 N0 M0
B T2a N0 M0
Stage IIA T2b N0 M0
T1 N1 M0
T2a N1 M0
Stage IIB T2b N1 M0
T3 N0 M0
Stage IIIA T1-2 N2 M0
T3 N1-2 M0
T4 N0-1 M0
Stage IIIB T1-2 N3 M0
T3 N3 M0
T4 N2-3 M0
Stage IV Any T Any N M1a
Any T Any N M1b
AJCC = American Joint Committee on Cancer.



Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:299-330[26] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2013;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 5, 2011.[25]



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