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Lung cancer, small cell: Treatment - Health Professional Information [NCI PDQ]
Purpose of This PDQ SummaryThis PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of small cell lung cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board. Information about the following is included in this summary:
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions. Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations. This summary is available in a patient version, written in less technical language, and in Spanish. General InformationNote: Separate PDQ summaries on Non-Small Cell Lung Cancer Treatment; Lung Cancer Prevention; and Lung Cancer Screening are also available. Note: Estimated new cases and deaths from lung cancer (small cell and non-small cell combined) in the United States in 2008:[1]
Without treatment, small cell lung cancer (SCLC) has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. Compared with other cell types of lung cancer, SCLC has a greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and radiation therapy. Because patients with small cell lung cancer tend to develop distant metastases, localized forms of treatment, such as surgical resection or radiation therapy, rarely produce long-term survival.[2] With incorporation of current chemotherapy regimens into the treatment program, however, survival is unequivocally prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. Furthermore, about 10% of the total population of patients remains free of disease during 2 years from the start of therapy, the time period during which most relapses occur. Even these patients, however, are at risk of dying from lung cancer (both small- and non-small cell types).[3] The overall survival at 5 years is 5% to 10%.[3,4,5] LIMITED-STAGE DISEASE At the time of diagnosis, approximately 30% of patients with SCLC will have tumor confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes. These patients are designated as having limited-stage disease, and most 2-year disease-free survivors come from this group. In limited-stage disease, median survival of 16 to 24 months with current forms of treatment can reasonably be expected.[6,7,8] A small proportion of patients with limited-stage disease may benefit from surgery with or without adjuvant chemotherapy; these patients have an even better prognosis. EXTENSIVE-STAGE DISEASE Patients with tumors that have spread beyond the supraclavicular areas are said to have extensive-stage disease and have a worse prognosis than patients with limited-stage disease. Median survival of 6 to 12 months is reported with currently available therapy, but long-term disease-free survival is rare. PROGNOSTIC FACTORS The pretreatment prognostic factors that consistently predict for prolonged survival include good performance status, female gender, and limited-stage disease.[4,9,10] Patients with involvement of the central nervous system or liver at the time of diagnosis have a significantly worse outcome.[4,9,10,11] In general, patients who are confined to bed tolerate aggressive forms of treatment poorly, have increased morbidity, and rarely attain 2-year disease-free survival; however, patients with poor performance status can often derive significant palliative benefit and prolongation of survival from treatment. Regardless of stage, the current prognosis for patients with SCLC is unsatisfactory even though considerable improvements in diagnosis and therapy have been made during the past 10 to 15 years. All patients with this type of cancer may appropriately be considered for inclusion in clinical trials at the time of diagnosis. Information about ongoing clinical trials is available from the NCI Web site.
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Cellular ClassificationReview of pathologic material by an experienced lung cancer pathologist is important prior to initiating treatment of any patient with small cell lung cancer (SCLC). The intermediate subtype of SCLC and the more readily recognized lymphocyte-like or oat cell subtype are equally responsive to treatment. The current classification of subtypes of SCLC is:[1]
Neuroendocrine carcinomas of the lung represent a spectrum of disease. At one extreme is SCLC, which has a poor prognosis. At the other extreme are bronchial carcinoids, which have an excellent prognosis after surgical excision.[2] Between these extremes is an unusual entity called well-differentiated neuroendocrine carcinoma of the lung.[3] It has been referred to as malignant carcinoid, metastasizing bronchial adenoma, pleomorphic carcinoid, nonbenign carcinoid tumor, and atypical carcinoid. Like SCLC, it occurs primarily in cigarette smokers, but it metastasizes less frequently. The 5-year survival rate is more than 50% in some series, and surgical cure appears possible in most stage I patients. Careful diagnosis is important, however, since the differential pathologic diagnosis from SCLC may be difficult.
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Stage InformationStaging procedures are important in distinguishing patients who have disease limited to their thorax from those who have distant metastases. Determining the stage of cancer by nonsurgical means allows a better assessment of prognosis and identifies sites of tumor that can be evaluated for response. Also, the choice of treatment is usually influenced by stage, particularly when chest radiation therapy or surgical excision is added to chemotherapy for patients with limited-stage disease. Staging procedures commonly used to document distant metastases include bone marrow examination, computed tomographic (CT) or magnetic resonance imaging scans of the brain, CT scans of the chest and the abdomen, and radionuclide bone scans. Because occult or overt metastatic disease is present at diagnosis in most patients, survival is usually not affected by small differences in the amount of locoregional tumor involvement. The detailed TNM staging system developed for lung cancer by the American Joint Committee on Cancer is not commonly employed in patients with small cell lung cancer (SCLC). (Refer to the PDQ summary on Non-Small Cell Lung Cancer Treatment for more information.) A simple two-stage system developed by the Veterans Administration Lung Cancer Study Group is more commonly used for staging SCLC patients. LIMITED-STAGE DISEASE Limited-stage SCLC means tumor confined to the hemithorax of origin, the mediastinum, and the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. No universally accepted definition of this term is available, and patients with pleural effusion, massive pulmonary tumor, and contralateral supraclavicular nodes have been both included within and excluded from limited stage by various groups. EXTENSIVE-STAGE DISEASE Extensive-stage SCLC means tumor that is too widespread to be included within the definition of limited-stage disease above. Patients with distant metastases (M1) are always considered to have extensive-stage disease.[1,2]
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Treatment Option OverviewNote: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.) The majority of patients with small cell lung cancer (SCLC) die of their tumor despite the best available treatment. Most of the improvements in the survival of patients with SCLC are attributable to clinical trials that have attempted to improve on the best available and most accepted therapy. Patient entry into such studies is highly desirable. Treatments under clinical evaluation in SCLC include studies of the timing of thoracic radiation therapy (for patients with limited-stage disease) and studies evaluating the role of surgery for stage I patients in conjunction with varying drug doses in current regimens, using different schedules of chemotherapeutic agents, and using new drug regimens composed of standard and new agents.[1] Information about ongoing clinical trials is available from the NCI Web site. Chemotherapy improves the survival of patients with limited-stage or extensive-stage SCLC, but it is curative in only a minority of patients.[1,2] Prospective randomized trials have not demonstrated a consistent survival advantage for patients treated with higher doses of chemotherapy.[3,4] One retrospective review of chemotherapy trials did not show consistent evidence for improved response rates or survival with more dose-intensive chemotherapy regimens.[5][Level of evidence: 1iiA] Even chemotherapy of the intensity used in autologous bone marrow transplant regimens has not clearly been shown to improve survival in patients with SCLC.[6] An intergroup study that compared the combination of dose-intensive cisplatin, vincristine, doxorubicin, and etoposide with standard doses of cyclophosphamide, doxorubicin, vincristine/etoposide, and cisplatin found that the more dose-intensive regimen produced a higher response rate but at the cost of increased treatment-related mortality and did not result in improved progression-free or overall survival.[7][Level of evidence: 1iiA]
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Limited-Stage Small Cell Lung CancerNote: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.) In patients with limited-stage small cell lung cancer (SCLC), combination chemotherapy produces results that are clearly superior to single-agent treatment, and moderately intensive doses of drugs are superior to doses that produce only minimal or mild hematologic toxic effects. Current programs yield overall objective response rates of 65% to 90% and complete response rates of 45% to 75%. Because of the frequent presence of occult metastatic disease, chemotherapy is the cornerstone of treatment for patients with limited-stage SCLC. Combinations containing two or more drugs are needed for maximal effect. Mature results of prospective randomized trials suggest that combined modality therapy produces a modest but significant improvement in survival compared with chemotherapy alone. Two meta-analyses showed an improvement in 3-year survival rates of about 5% for those receiving chemotherapy and radiation therapy compared with those receiving chemotherapy alone.[1,2] Most of the benefit occurred in patients younger than 65 years. Combined modality treatment is associated with increased morbidity and, in some trials, increased treatment-related mortality from pulmonary and hematologic toxic effects; proper administration requires close collaboration between medical and radiation oncologists.[3] In general, those studies (SWOG-S0124) showing a positive effect for combined modality therapy employed thoracic radiation therapy early in the course of treatment and concurrently with chemotherapy.[3,4,5,6] Studies strongly suggest that minimal tumor doses in the range of 40 Gy to 45 Gy or more (standard fractionation) are necessary to effectively control tumors in the thorax. The combination of etoposide and cisplatin chemotherapy with concurrent chest radiation therapy has now been used in multiple single institutional studies and in cooperative group studies. These studies have consistently achieved median survivals of 18 to 24 months and 40% to 50% 2-year survival with less than a 3% treatment-related mortality.[3,4,5,6,7] Once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. One randomized study showed a modest survival advantage in favor of twice-daily radiation therapy given for 3 weeks, compared with once-daily radiation therapy given for 5 weeks (26% vs. 16% at 5 years, P = .04). Although single daily fractions to higher doses are feasible, their clinical benefits are yet to be defined.[8][Level of evidence: 3iiiA] Esophagitis was increased with twice-daily treatment.[9][Level of evidence: 1iiA] The current standard treatment of patients with limited-stage SCLC should be a combination containing etoposide and cisplatin plus chest radiation therapy administered during the first or second cycle of chemotherapy administration. The relative effectiveness of two- to five-drug regimens and different schedules of chest radiation therapy appear to be similar. A representative selection of regimens incorporating chemotherapy plus chest radiation therapy are listed below. The use of alternating chemotherapy regimens has not proven more effective than the consistent administration of a single regimen.[3,6,7,10,11,12] The optimal duration of chemotherapy for patients with limited-stage SCLC is not clearly defined, but no improvement exists in survival after the duration of drug administration exceeds 3 to 6 months.[3,7,13] No evidence is available from randomized trials EORTC-LCCG and European Lung Cancer Working Party that maintenance chemotherapy prolongs survival for patients with limited-stage SCLC.[10,14] Patients presenting with superior vena cava syndrome are treated with combination chemotherapy with or without radiation therapy.[15,16] (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.) A small minority of limited-stage patients with adequate pulmonary function and with tumor pathologically confined to the lung of origin, or the lung and ipsilateral hilar lymph nodes, may possibly benefit from surgical resection with or without adjuvant chemotherapy.[17,18,19,20] Patients treated with chemotherapy with or without chest radiation therapy who have achieved a complete remission can be considered for administration of prophylactic cranial irradiation (PCI). Patients whose cancer can be controlled outside the brain have a 60% actuarial risk of developing central nervous system metastases within 2 to 3 years after starting treatment.[21,22] The majority of these patients relapse only in their brain, and nearly all of those who relapse in their central nervous system die of their cranial metastases.[3,7,22] The risk of developing central nervous system metastases can be reduced by more than 50% by the administration of PCI in doses of 24 Gy.[22] A meta-analysis of seven randomized trials evaluating the value of PCI in patients in complete remission reported improvement in brain recurrence, disease-free survival, and overall survival (OS) with the addition of PCI. The 3-year OS was improved from 15% to 21% with PCI.[22][Level of evidence: 1iiA] Retrospective studies have shown that long-term survivors of SCLC (>2 years from the start of treatment) have a high incidence of central nervous system impairment.[23,24,25] Prospective studies have shown that patients treated with PCI do not have significantly worse neuropsychological function than patients not treated.[22] In addition, the majority of patients with small cell lung cancer have neuropsychological abnormalities present before the start of cranial irradiation and have no detectable decline in their neurological status for as long as 2 years after the start of their cranial irradiation.[26] Patients treated for SCLC continue to have declining neuropsychologic function after 2 years from the start of treatment.[23,24,25] Additional neuropsychologic testing of patients beyond 2 years from the start of treatment will be needed before concluding that PCI does not contribute to the decline in intellectual function. STANDARD TREATMENT OPTIONS:
TREATMENT OPTIONS UNDER CLINICAL EVALUATION: Areas of active clinical evaluation for patients with limited-stage SCLC include new drug regimens, variation of drug doses in current regimens, surgical resection of the primary tumor, new radiation therapy schedules and techniques (e.g., three-dimensional treatment planning), and timing of thoracic radiation.[27,28] Information about ongoing clinical trials is available from the NCI Web site. Current Clinical Trials Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with limited stage small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria. General information about clinical trials is also available from the NCI Web site.
References:
Extensive-Stage Small Cell Lung CancerNote: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.) As in limited-stage small cell cancer (SCLC), chemotherapy should be given as multiple agents in doses associated with at least moderate toxic effects to produce the best results in patients with extensive-stage disease. Doses and schedules used in current programs yield overall response rates of 70% to 85% and complete response rates of 20% to 30% in patients with extensive-stage disease. Since overt disseminated disease is present, combination chemotherapy is the cornerstone of treatment of this stage of SCLC. Combinations containing two or more drugs are needed for maximal benefit. The relative effectiveness of most two- to four-drug combination programs appears similar, and a large number of potential combinations are available. Some studies (ECOG-7593) have administered two of these or other regimens in alternating sequences, but no proof exists that this strategy yields substantial survival improvement.[1,2,3,4] A phase III study conducted in Japan compared a standard two-drug regimen of cisplatin and etoposide with a combination of cisplatin and irinotecan.[5][Level of evidence: 1iiA] The planned enrollment was 230 patients younger than 70 years, however, the trial was stopped early with a total of 154 patients when an interim analysis found a significant difference favoring the irinotecan arm. The median survival in the cisplatin and irinotecan group was 12.8 months (95% confidence interval [CI], 11.7–15.2 months), while it was 9.4 months in the cisplatin and etoposide arm (95% CI, 8.1–10.8 months). The 2-year survival was 19.5% versus 5.2%. Hematologic toxic effects were more severe in the etoposide and cisplatin treated patients, while gastrointestinal toxic effects were worse in the irinotecan-treated and cisplatin-treated patients. However, no difference in response rate, median time-to-progression, or overall survival (OS) was reported from a second study that involved 331 patients with extensive disease and compared cisplatin and etoposide with a modified weekly regimen of cisplatin and irinotecan.[6][Level of evidence: 1iiA] The modified weekly irinotecan/cisplatin regimen resulted in less myelosuppression but more diarrhea and vomiting.[6][Level of evidence: 1iiA] A third study (SWOG-S0124) comparing irinotecan versus etoposide with cisplatin using doses and schedules similar to the original Japanese study is under way. In a randomized trial of 784 patients, the combination of oral topotecan given with cisplatin for 5 days was not found to be superior to etoposide and cisplatin.[7] The 1-year survival rate was 31% (95% CI, 27%–36%) and was deemed to be noninferior as the difference of -0.03 met the predefined criteria of no more than10% absolute difference in 1-year survival. The optimal duration of chemotherapy is not clearly defined, but no obvious improvement in survival occurs when the duration of drug administration exceeds 6 months.[8,9] No clear evidence is available from reported data that maintenance chemotherapy will improve survival duration.[10,11,12,13] Combination chemotherapy plus chest radiation therapy does not appear to improve survival compared with chemotherapy alone in patients with extensive-stage SCLC. Radiation therapy, however, plays an extremely important role in palliation of symptoms of the primary tumor and of metastatic disease, particularly brain, epidural, and bone metastases. Chest radiation therapy is sometimes given for superior vena cava syndrome, but chemotherapy alone, with irradiation reserved for nonresponding patients, is appropriate initial treatment. (Refer to the PDQ summary on Cardiopulmonary Syndromes for more information.) Brain metastases are appropriately treated with whole-brain radiation therapy. Intracranial metastases from small cell carcinoma, however, may respond to chemotherapy as readily as metastases in other organs.[13,14] Patients with small cell lung cancer treated with chemotherapy with or without chest irradiation, who have achieved a complete remission, can be considered for administration of prophylactic cranial irradiation (PCI). Patients whose cancer can be controlled outside the brain have a 60% actuarial risk of developing central nervous system metastases within 2 to 3 years after starting treatment.[15,16] The majority of these patients relapse only in their brain, and nearly all of those who relapse in their central nervous system die of their cranial metastases.[16,17,18] The risk of developing central nervous system metastases can be reduced by more than 50% by the administration of PCI in doses of 24 Gy.[16] A meta-analysis of seven randomized trials evaluating the value of PCI in patients in complete remission reported improvement in brain recurrence, disease-free survival, and OS with the addition of PCI. The 3-year OS was improved from 15% to 21% with PCI.[16][Level of evidence: 1iiA] Retrospective studies have shown that long-term survivors of SCLC (>2 years from the start of treatment) have a high incidence of central nervous system impairment.[19,20,21] Prospective studies, however, have shown that patients treated with PCI do not have detectably different neuropsychological function than patients not treated.[16] In addition, the majority of patients with SCLC have neuropsychological abnormalities present before the start of cranial irradiation and have no detectable decline in their neurological status for as long as 2 years after the start of their cranial irradiation.[22] Patients treated for SCLC continue to have declining neuropsychologic function after 2 years from the start of treatment.[19,20,21] Additional neuropsychologic testing of patients beyond 2 years from the start of treatment will be needed before concluding that PCI does not contribute to the decline in intellectual function. Many more patients with extensive-stage SCLC have greatly impaired performance status at the time of diagnosis when compared with patients with limited-stage disease. Such patients have a poor prognosis and tolerate aggressive chemotherapy or combined modality therapy poorly. Single-agent intravenous, oral, and low-dose biweekly regimens have been developed for these patients.[23,24,25,26] Prospective randomized studies, however, have shown that patients with a poor prognosis who are treated with conventional regimens live longer than those treated with the single-agent or low-dose regimens.[25,26,27] STANDARD TREATMENT OPTIONS:
TREATMENT OPTIONS UNDER CLINICAL EVALUATION: Areas of active clinical evaluation in extensive-stage SCLC include evaluation of new drug regimens, dose intensity, alternative drug schedules, and high-dose chemotherapy. A meta-analysis of long-term outcomes in extensive-stage disease did not show consistent evidence for improved response rates or survival for more intense chemotherapy regimens.[44][Level of evidence: 1iiA] Information about ongoing clinical trials is available from the NCI Web site. Current Clinical Trials Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with extensive stage small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria. General information about clinical trials is also available from the NCI Web site.
References:
Recurrent Small Cell Lung CancerNote: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.) The prognosis for patients with small cell lung cancer (SCLC) that has progressed despite chemotherapy is exceedingly poor regardless of stage. Expected median survival is 2 to 3 months. These patients should be considered for palliative therapy or clinical trials. Patients who are primarily resistant to chemotherapy, and those who have received multiple chemotherapy regimens, rarely respond to additional treatment. Patients who have initially responded and relapsed more than 6 months following initial treatment, however, are more likely to respond to additional chemotherapy. While no single chemotherapy regimen should be considered standard, those that have shown activity as second line treatment include oral etoposide, etoposide/cisplatin, cyclophosphamide/doxorubicin/vincristine (CAV), lomustine/methotrexate, paclitaxel, and topotecan.[1,2,3,4,5,6,7,8,9][Level of evidence: 3iiiDiv] A randomized comparison of second-line treatment with either CAV or topotecan reported no significant difference in response rates or survival, but palliation of common lung cancer symptoms was better with topotecan.[8][Level of evidence: 1iiC] Some patients with intrinsic endobronchial obstructing lesions or extrinsic compression caused by tumor have achieved successful palliation with endobronchial laser therapy (for endobronchial lesions only) and/or brachytherapy.[10] Expandable metal stents can be safely inserted under local anesthesia via the bronchoscope, which results in improved symptoms and pulmonary function in patients with malignant airways obstruction.[11] Patients with progressive intrathoracic tumor after failing initial chemotherapy can achieve significant tumor responses, palliation of symptoms, and short-term local control with external-beam radiation therapy. Only the rare patient, however, will experience long-term survival following salvage radiation therapy.[12] Patients with central nervous system recurrences can often obtain palliation of symptoms with radiation therapy and/or additional chemotherapy. The majority of patients treated with radiation therapy obtain objective responses and improvement following radiation therapy.[13] A retrospective review showed that 43% of patients treated with additional chemotherapy at the time of central nervous system relapse respond to second-line chemotherapy.[14] STANDARD TREATMENT OPTIONS:
Current Clinical Trials Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent small cell lung cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria. General information about clinical trials is also available from the NCI Web site.
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Get More Information From NCICALL 1-800-4-CANCER For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions. CHAT ONLINE The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer. WRITE TO US For more information from the NCI, please write to this address:
SEARCH THE NCI WEB SITE The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results. There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment. FIND PUBLICATIONS The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615. Changes to This Summary (02/22/2008)The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. GENERAL INFORMATION Updated statistics with estimated new cases and deaths for 2008 (cited American Cancer Society). More InformationABOUT PDQ
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IMPORTANT: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). Date Last Modified: 2008-02-22
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