The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.
Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned.
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.
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.
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.
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.
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.