Chemotherapy and radiotherapy are the keys of current management of SCLC. For many years, the diagnosis of small cell lung cancer has been considered a contraindication to surgery because radiotherapy was at least equivalent in terms of local control and the rate of resectability of SCLC patients was poor. The role of surgery has been defined by evidence accumulated in the last 30 years but conclusions are limited by the fact that the most important studies are dated and conducted when the main staging tool was exploratory thoracotomy. The rationale for surgery in the context of SCLC is based on 3 factors: 1) Several historical series on patients operated for limited SCLC reported some long term survivors, showing that permanent cure can be achieved. For this reason, it is now accepted that for the rare patients with very limited stage disease (T1-T2 tumors) surgical resection followed by platinum-based chemotherapy could be offered. 2) After chemotherapy and radiotherapy, the rate of local relapse is 20-30%. The assumption that surgery might be superior to radiotherapy in local control of limited SCLC has been suggested but not still proved. 3) Surgery can precisely assess pathological response to chemotherapy, identify carcinoids erroneously diagnosed as SCLC, treat the NSCLC component of tumors with a mixed histology. In the case of planned surgery, preoperative investigations should be completed by MRI of the brain, mediastinoscopy (to rule out subclinical N2/N3 patients) and probably PET scan. Even if some controversies exist, it is accepted that surgery can be proposed as the first treatment in patents with T1-T2 lesions without sign of lymph nodes involvement, followed by adjuvant chemotherapy. Surgery in stage II and III must be planned on a multidisciplinary basis, in the context of controlled clinical trials.
Attention to palliation is imperative in the management of patients with lung cancer, given the burden of symptoms and the incurable nature of the illness in a large proportion of patients. Focus on symptom control and enhancing quality of life can and should coexist with active treatment of the cancer process and attempts at prolongation of life. This article reviews some of the methodological issues in assessing palliation, and presents the evidence for the role of various therapeutic modalities in palliation of thoracic symptoms, including external beam radiotherapy, brachytherapy, chemotherapy, photodynamic therapy, and vascular stents. Palliation of metastatic disease, particularly bone and brain metastases, is also reviewed.
The majority of patients with non-small cell lung cancer have locally advanced and metastatic disease at diagnosis. Combination platinum-based chemotherapy is the standard treatment for patients with advanced disease who have a performance status of 0-1. Chemotherapy is superior to supportive care alone in terms of survival, palliation of symptoms, and in many studies, improving quality of life. Newer third generation therapies such as paclitaxel, docetaxel, vinorelbine, and gemcitabine have been proven effective as single agents with minimal toxicity, compared with supportive care alone. In combination with platinum, these agents produce higher response rates than older platinum-based regimens, are associated with additional survival benefits, and are generally more convenient and less toxic for patients. Newer nonplatinum doublets appear equivalent to newer platinum-regimens and have expanded the options available for patients. Targeted agents are promising and may soon offer patients more effective and less toxic therapies. Progress in treatment in the advanced setting has led to advances in the care of locally advanced disease. Combination chemoradiotherapy is a standard treatment for locally advanced disease, and studies with newer agents are in progress.
Seminars in Surgical OncologyVolume 21, Issue 4 p. 221-222 Foreword: Chemoradiation for GI cancers Tyvin A. Rich MD, Corresponding Author Tyvin A. Rich MD Guest Editor TAR4D@hscmail.mcc.virginia.edu Charlottesville, VirginiaDepartment of Radiation Oncology, Box 800383, University of Virginia Health System, Charlottesville, Virginia 22908.Search for more papers by this author Tyvin A. Rich MD, Corresponding Author Tyvin A. Rich MD Guest Editor TAR4D@hscmail.mcc.virginia.edu Charlottesville, VirginiaDepartment of Radiation Oncology, Box 800383, University of Virginia Health System, Charlottesville, Virginia 22908.Search for more papers by this author First published: 19 November 2003 https://doi.org/10.1002/ssu.10047AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issue4November 2003Pages 221-222 RelatedInformation
Seminars in Surgical OncologyVolume 21, Issue 1 p. 1-2 Foreword: TNM sixth edition: New developments† Leslie H. Sobin MD, Corresponding Author Leslie H. Sobin MD Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DCDepartment of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DCSearch for more papers by this author Leslie H. Sobin MD, Corresponding Author Leslie H. Sobin MD Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DCDepartment of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DCSearch for more papers by this author First published: 11 August 2003 https://doi.org/10.1002/ssu.10013 † This article is a U.S. Government work and, as such, is in the public domain in the United States of America. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue12003Pages 1-2 RelatedInformation
Substantial improvements in treatment outcome for limited-disease small-cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high-dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival.
The TNM Classification describes the anatomic extent of cancer. TNM's ability to separately classify the individual tumor (T), node (N), and metastasis (M) elements and then group them into stages differs from other cancer staging classifications (e.g., Dukes), which are only concerned with summarized groups. The objectives of the TNM Classification are to aid the clinician in the planning of treatment, give some indication of prognosis, assist in the evaluation of the results of treatment, and facilitate the exchange of information. During the past 50 years, the TNM system has evolved under the influence of advances in diagnosis and treatment. Radiographic imaging (e.g., endoscopic ultrasound for the depth of invasion of esophageal and rectal tumors) has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Developments in multimodality therapy have increased the importance of the "y" symbol and the R (residual tumor) classification. New surgical techniques have resulted in the elaboration of the sentinel node (sn) symbol. The use of immunohistochemistry has resulted in the classification of isolated tumor cells and their distinction from micrometastasis. The most important challenge facing users of the TNM Classification is how it should interface with the large number of non-anatomic prognostic factors that are currently in use or under study. As non-anatomic prognostic factors become widely used, the TNM system provides an inviting foundation upon which to build a prognostic classification; however, this carries a risk that the system will be overwhelmed by a variety of prognostic data. An anatomic extent-of-disease classification is needed to aid practitioners in selecting the initial therapeutic approach, stratifying patients for therapeutic studies, evaluating non-anatomic prognostic factors at specific anatomic stages, comparing the weight of non-anatomic factors with extent of disease, and communicating the extent of disease data in a uniform manner. Methods are needed to express the overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, while permitting the TNM system to remain intact and distinct. This article discusses examples of such approaches.
Gastric cancer has a poor prognosis. It is often diagnosed at an advanced stage, and potentially curative treatments often can not be exercised. Even when a curative surgical resection is possible, only a minority of patients survive beyond 5 years, and locoregional failures are frequent among patients undergoing curative resections. Recently, the use of postoperative adjuvant chemoradiotherapy has yielded some notable benefits. Earlier studies have shown survival benefits in patients undergoing chemoradiotherapy for locally advanced unresectable gastric cancer. The recently reported Intergroup 0116 trial compared surgery alone with surgery plus postoperative chemotherapy plus chemoradiotherapy. Superior overall and disease-free survival rates among patients given combined-modality postoperative therapy were observed. These results established a new standard of care for patients following resection of gastric carcinoma. Preoperative combined-modality chemoradiotherapy may improve resectability, and is under investigation at the University of Texas M. D. Anderson Cancer Center. The development of novel radioenhancers and the selection of therapy on the basis of molecular determinants of response may result in much-needed advances in this field.
Diagnosis, prognosis, and treatment are the three core elements of the art of medicine. Modern medicine pays more attention to diagnosis and treatment but prognosis has been a part of the practice of medicine much longer than diagnosis. Cancer is a heterogeneous group of disease characterized by growth, invasion and metastasis. To plan the management of an individual cancer patient, the fundamental knowledge base includes the site of origin of the cancer, its morphologic type, and the prognostic factors specific to that particular patient and cancer. Most prognostic factors literature describes those factors that directly relate to the tumor itself. However, many other factors, not directly related to the tumor, also affect the outcome. To comprehensively represent these factors we propose three broad groupings of prognostic factors: 'tumor'-related prognostic factors, 'host'-related prognostic factors, and 'environment'-related prognostic factors. Some prognostic factors are essential to decisions about the goals and choice treatment, while others are less relevant for these purposes. To guide the use of various prognostic factors we have proposed a grouping of factors based on their relevance in everyday practice; these comprise 'essential,' 'additional,' and 'new and promising factors.' The availability of a comprehensive classification of prognostic factors assures an ordered and deliberate approach to the subject and provide safeguard against skewed approaches that may ignore large parts of the field. The current attention to tumor factors has diminished the importance of 'patient' (i.e., 'host'), and almost completely overshadows the importance of the 'environment'. This ignores the fact that the latter presents the greatest potential for immediate impact. The acceptance of a generic prognostic factor classification would facilitate communication and education about this most important subject in oncology.
The depiction of prognosis is one of the main activities and a mainstay in medical practice. In cancer, as in other diseases, the prognosis differs for a variety of situations and evolves with time and with medical interventions. Although most commonly described at diagnosis, prognosis may be defined at any time during the course of the disease and for any endpoint including response to therapy, failure of treatment, survival, or preservation of function, and so forth. To facilitate the accurate portrayal of the future, the prognosis should be defined within a specific setting, referred to as a 'management scenario'. In the concept of a management scenario, the prognosis is defined using systematically considered prognostic factors, interventions and the outcome of interest. A deliberate and careful determination of prognosis is essential to clinical decision making and patient care. We illustrate the use of the concept of management scenario in several clinical examples.
Locally advanced non-small cell lung carcinoma (NSCLC) presents enormous challenges to clinicians and researchers. Because of the absence of metastatic disease, it is a potentially curable condition, greatly differentiating it from stage IV NSCLC. The median and actuarial survival rates are poor, though clearly improved in the past decade, and clearly better than several other types of locally advanced malignancies (e.g., pancreatic cancer, glioblastoma). As demonstrated in Table I, the combination of chemotherapy and radiotherapy has earned the designation of "standard of care" for most good-performance-status patients with locally advanced NSCLC. It is likely that improvements in radiotherapy have also contributed to the enhanced survival and local control rates in this disease. With concurrent chemoradiotherapy, the majority of patients can receive a substantial local response (Fig. 1). Many achieve durable local control, only to succumb to eventual distant metastatic failure. There remains much room for improvement, and there are several avenues for clinical and translational research that offer promise. These include new systemic chemotherapy options (and newer ways of combining these drugs with radiotherapy), improvements in radiotherapy fractionation and dose intensity, methods of protection from chemoradiotherapy toxicity, specific therapies to prevent brain metastatic failure, and the integration of biologically targeted molecules into chemoradiation programs. This article summarizes the advances in the treatment of locally advanced NSCLC over the past several decades and explores some of the many remaining controversies and areas for future investigation.
Positron emission tomography (PET) represents a dramatic advance in the imaging of lung cancer. It is valuable for the diagnosis, staging, prognosis, and restaging of disease, and is most useful in patients considered for potentially curative therapy for non-small-cell lung cancer (NSCLC). In this work the current status and potential future applications of PET scanning in lung cancer are discussed. The relevant literature is also discussed, with an emphasis on studies with clinical applicability. Most of these studies involved the use of 18F-fluorodeoxyglucose (FDG). Numerous studies of the use of PET to assess undiagnosed pulmonary nodules have reported significant improvements in accurate diagnosis or exclusion of malignancy compared to conventional structural imaging alone. All of these studies, including metaanalysis, have shown that PET is more accurate than CT-based structural imaging in staging the mediastinum in surgical candidates. PET may have value in radiotherapy planning, and PET-based staging more accurately predicts survival in radiotherapy-treated patients than conventional staging. The rate of unsuspected distant metastasis detection in stage III disease exceeds 20%. PET also facilitates an accurate assessment of response in patients treated with radical chemoradiation or neoadjuvant therapy prior to surgery. PET has rapidly become an indispensable part of the evaluation of patients with potentially curable lung cancer; however, more work is required to define its role.
Recent research advances in cancer and molecular biology have furthered our understanding of the etiology and natural history of lung cancer. Through translational research, a growing understanding of the molecular changes that underlie cancer progression has contributed to the development of novel molecular approaches for early detection, further defining prognosis, refining treatment schedules, identifying new therapeutic targets, and identifying patients at risk for treatment-related toxicity from aggressive therapy, such as pneumonitis and esophagitis. In this article, we review progress in molecular/gene screening and prognosis, and we present a clinical study, based on preclinical research, in which we apply low-dose radiosensitizing paclitaxel for locally advanced non-small-cell lung cancer (NSCLC); this resulted in superior local tumor control while keeping treatment toxicity low. We also review progress made in identifying cytokines: interleukin [IL]-1alpha, IL-6, and transforming growth factor [TGF] beta as markers for lung cancer treatment-related radiation pneumonitis. Finally, we summarize different targeted therapy approaches and discuss their application to clinical trials. Irrespective of the slow progress toward clinical improvements, we have gained much knowledge through translational research using new molecular and biologic technology. We believe that knowledge of lung cancer biology will continue to provide the foundation for future improvements in lung cancer treatment.
In preparation for the 6th edition of the UICC and AJCC publications on TNM staging, all data regarding sites of the digestive system (gastrointestinal and hepatobiliary) were reviewed by expert site teams. Although the information for several sites (esophagus, small bowel, and anal canal) required no change from the 5th editions, significant changes were recommended for the pancreas, liver, extrahepatic biliary system, colon, and rectum. Minor but important changes were made regarding gastric and peri-ampullary malignancies. The changes were made based on new prognostic information and analysis of available data sets. The importance of large national registries, such as the National Cancer Data Base (NCDB; American College of Surgeons Commission on Cancer), is stressed.
Seminars in Surgical OncologyVolume 21, Issue 2 p. 61-63 Foreward: Cancer of the lung in the new millenium Branislav Jeremic MD, PhD, Corresponding Author Branislav Jeremic MD, PhD bjeremic@lrz.tu-muenchen.de Department of Radiation Oncology, Klinikum rechts der Isar, Munich, GermanyDepartment of Radiation Oncology, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, D-81675 Munich, Germany.Search for more papers by this author Branislav Jeremic MD, PhD, Corresponding Author Branislav Jeremic MD, PhD bjeremic@lrz.tu-muenchen.de Department of Radiation Oncology, Klinikum rechts der Isar, Munich, GermanyDepartment of Radiation Oncology, Klinikum rechts der Isar, Technical University Munich, Ismaninger Strasse 22, D-81675 Munich, Germany.Search for more papers by this author First published: 18 September 2003 https://doi.org/10.1002/ssu.10022AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue2September 2003Pages 61-63 RelatedInformation
Extensive-stage small-cell lung cancer (ES-SCLC) continues to be a difficult management issue. While response rates to therapy are relatively high, durable responses are rare, and long-term survival rates are dismal. Although many attempts have been made to develop new therapies, cisplatin-based combination chemotherapy remains the mainstay in the management of these patients. In this review we highlight recent developments in the treatment and management of this malignancy, and discuss future prospects in treatment.
Lung cancer is a common disease in elderly patients, and the increase in the size of the elderly population will lead to an increased proportion of elderly among lung cancer patients in the future. The prognosis of lung cancer is still poor, but curative approaches are feasible for patients with local stage NSCLC and for some patients with limited disease (LD) SCLC. The evidence for these curatively-intended approaches is derived from studies that are usually performed with highly selected patients. Elderly patients are underrepresented, and in daily clinical practice elderly patients are less likely to be treated with full standard approaches. We used the data from studies that focused particularly on the elderly, or provided subgroup information on age, to analyze the feasibility of applying current standard approaches to the elderly. We also discuss alternative approaches. Age alone is a very uncertain prognostic criterion for outcome or tolerability of treatment. It is much more important to obtain a comprehensive geriatric assessment of each individual patient. When adequate patient selection is provided, standard treatment approaches appear to be feasible for elderly (>70 years) patients with good performance status.
Recurrence is a common event after treatment of lung cancer. Retreatment options depend on previous therapies, location of recurrence, and physical condition of the patient. Locoregional relapse can be treated the same way as initial lung cancer, including surgery, radiotherapy (RT), and chemotherapy (CHT), or combined treatment. Approximately 1% to 2% of all recurrent lung cancer is treated with curative reoperation, with somewhat dismal results. RT has been used for either postsurgical or post-RT locoregional recurrences. In the former case, external beam RT was particularly effective in isolated bronchial stump recurrences, with median survival time of approximately 28.5 months and a 5-year survival of approximately 31.5%. In the latter case, reirradiation, generally with endobronchial brachytherapy, was successful in palliation of intrathoracic symptoms (in at least two-thirds of cases), carrying a low incidence of radiation pneumonitis (up to 5%) although cumulative doses went up to 120-150 Gy. Besides external beam RT, endobronchial RT was used to treat symptomatic intraluminal recurrences, with the vast majority of studies using high-dose rate brachytherapy. Finally, CHT has been used in relapsed/refractory advanced or metastatic non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with the major emphasis on the third-generation drugs that show good response after previously used platinum-based CHT.
Conventional radiation therapy has had limited success in curing inoperable lung cancer due to poor local control. There is evidence to suggest that higher doses of radiation will improve local control. In order to safely deliver higher doses of thoracic radiation, advanced treatment techniques are required. Different biologic indices have been utilized to determine whether dose escalation can be safely accomplished, and the results have been reported from many institutions. Tumor motion control aids in treatment since it allows radiation oncologists to more accurately target tumors and therefore to spare more normal tissue from the radiation field. The imaging information from 18-FDG-PET scans also improves target delineation. Advanced treatment delivery techniques, such as three-dimensional conformal radiation therapy, intensity modulated radiation therapy, and stereotactic radiosurgery are also being used to safely escalate the radiation dose. This article explores the current literature on these issues and other advanced radiation therapy techniques.
