Extrapleural pneumonectomy for malignant mesothelioma.
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Dissection↗
Biomedical subjects
D J Sugarbaker
Publications and source records attributed to D J Sugarbaker.
Immunoblastic lymphoma of donor origin in the allograft after lung transplantation.
Posttransplant lymphoproliferative disorders (PTLD) are EBV-associated lymphoid neoplasms that are caused by the uncontrolled growth of EBV-infected B lymphocytes. The clinical presentation of PTLD can range from benign polygonal lymphoproliferative disorders to aggressive monoclonal immunoblastic lymphomas. In this report, we describe a seronegative lung transplant recipient who developed an immunoblastic lymphoma 4 months after lung transplantation from a seropositive donor. The neoplastic cells expressed B lymphocyte markers (CD19+, CD20+, sIgM+, kappa+) as well as the EBV antigen EBNA-2. A cell line with similar cytologic features spontaneously grew from in vitro cultures of the patient's peripheral blood mononuclear cells. The cell line and the lymphoma were EBV+, expressed a similar spectrum of B cell surface proteins, and had the donor's HLA haplotype. Analysis of immunoglobulin gene rearrangements and viral terminal repeat sequences revealed that the cell line and the tumor represented distinct B cell clones. Cultured peripheral blood mononuclear cells were restimulated in vitro with the EBV transformed cell line and tested for cytolytic activity. The host T cells demonstrated high levels of cytolytic activity against the tumor cell line that was abrogated by the addition of a anti-monomorphic HLA class I monoclonal antibody (mAb) (W6/32). These studies indicate that cells of donor origin can persist in the transplanted organ and may lead to an EBV-associated posttransplant lymphoma.
Antibodies, Monoclonal↗
Patterns of disease failure after trimodality therapy of nonsmall cell lung carcinoma pathologic stage IIIA (N2). Analysis of Cancer and Leukemia Group B Protocol 8935.
BACKGROUND: The impact of sequential trimodality therapy on the pattern of first site disease failure in pathologic Stage IIIA (N2) nonsmall cell lung carcinoma (NSCLC) was analyzed. METHODS: Seventy-four eligible patients with histologically documented Stage IIIA (N2) NSCLC underwent sequential trimodality therapy on Cancer and Leukemia Group B (CALGB) Protocol 8935. Treatment consisted of 2 cycles of induction cisplatin at 100 mg/m2 intravenously (i.v.) (Days 1 and 29) and vinblastine at 5 mg/m2 i.v. weekly for 5 weeks followed by surgery. Surgery included a thoracotomy with resection of the primary tumor and hilar lymph nodes and a mediastinal lymph node dissection. Patients with resected disease then received an additional a cycles of cisplatin at 100 mg/m2 i.v. and vinblastine at 5 mg/m2 i.v. biweekly for 2 total of 4 doses followed by consolidative thoracic irradiation. Patients with completely resected disease received 54 Gray (Gy) whereas those with incompletely resected disease received 59.4 Gy at 1.8 Gy/fraction (fx) once a day. Patients with unresectable disease underwent thoracic radiation therapy (TRT) treatments only to 59.4 Gy at 1.8 Gy/fx without any additional chemotherapy. Disease recurrence was determined by clinical, radiographic, or histologic criteria. Pattern of disease failure was identified by site of involvement at first recurrence as indicated by the CALGB Respiratory Follow-Up Form. RESULTS: Sixty-three of the 74 patients completed the induction chemotherapy as planned. Forty-six of the 63 patients underwent resection of disease whereas the remaining 17 were unresectable. Thirty-three of the 46 resected patients completed the entire adjuvant postoperative chemoradiation treatment as planned. Ten of 17 patients with unresectable disease completed postsurgical TRT. At a median follow-up interval of 27 months (range, 4-43), the 3-year overall survival and failure-free survival were 23% and 18%, respectively, for all 74 eligible patients. Overall, disease failure has occurred in 52 (70%) of the 74 eligible patients: local only: 13 (25%); distant only: 16 (31%); and both local and distant: 23 (44%), (P = not significant [NS]). Ten patients progressed during induction chemotherapy: local only: six patients; and both local and distant failure: four patients. Twenty-eight of 46 resected patients recurred: local only: 1 (4%); both local and distant failure: 11 (39%); and distant only: 16 (57%); (P < 0.001). Disease progression occurred in 14 of 17 patients with unresectable disease: local only: 6; both local and distant sites: 8. Among the 52 total patients experiencing disease relapse, isolated or combined local failure occurred commonly among patients during induction chemotherapy (n = 10, [28%]), in those with unresectable disease (n = 14, [39%]), or in those with resected disease (n = 12, [33%]), (P = NS). However, isolated or combined distant failure was more likely to occur among patients with resected disease (n = 27, [69%]) than either during induction chemotherapy (n = 4, [10%]) or in those with unresected disease (n = 8, [21%]), (P < 0.05). Among patients who relapsed, brain metastases occurred in 13 of 52 (25%) patients overall and in 12 of 28 (43%) patients with resected disease. CONCLUSIONS: Overall, disease failure was just as likely to occur in local, distant, or combined sites on CALGB Protocol 8935 using sequential trimodality therapy in the treatment of pathologic Stage IIIA (N2) NSCLC: Isolated or combined local failure occurred commonly during sequential tri-modality therapy whereas isolated or combined distant relapse was prevalent among patients with resected disease. In addition, isolated local failure was rare among patients with resected disease. The pattern of disease failure on CALGB Protocol 8935 reflects the biology of locoregional NSCLC as much as the therapeutic impact of trimodality therapy.
Adenocarcinoma↗
Chest wall invasive non-small cell lung cancer: patterns of failure and implications for a revised staging system.
BACKGROUND: To assess outcomes and patterns of failure for chest wall invasive non-small cell lung cancer (T3 or IIIA NSCLC), data were acquired prospectively on 47 consecutive patients at a single institution over 6 years. METHODS: Preresectional stagings included bone scan, head and chest/abdominal computed tomography, and mediastinoscopy. There were 25 superior sulcus tumors (radiation and/or chemotherapy followed by resection) and 22 other chest wall invasive NSCLCs (resection alone). RESULTS: There were no perioperative deaths. Seventeen patients (36%) had an operative complication (median length of stay increased from 7 to 12 days; p < 0.05). A complete pathologic resection was achieved for 44 of 47 patients (94%). The median survival was 38 months (actuarial 2- and 5-year survival rates of 62% and 50%, respectively). Median lengths of survival for superior sulcus and other chest wall tumors were 36 and > 60 months, respectively. Significant univariate predictors of decreased overall and cancer-free survival were poor performance status, positive margins, and positive lymph nodes. Recurrence was observed in 22 of 47 patients (46%) at a median of 8 months (range 2-24); patterns of failure were in the ipsilateral chest (n = 2; 4%) and at a distant site (n = 15; 32%) or both (n = 5; 11%). CONCLUSIONS: The operative risk for chest wall invasive NSCLC is acceptable, even after neoadjuvant therapy, allowing for a 94% complete resection rate. The survival of this subset of stage IIIA patients may warrant a reappraisal of the international staging system.
Adult↗
Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias.
BACKGROUND: Data were acquired prospectively on 136 consecutive patients undergoing pneumonectomy for cancer from 1988 to 1993, to define factors that increase the risk of major morbidity and postoperative cardiac dysrhythmias. METHODS: There were 81 patients (60%) with non-small cell lung cancer (standard pneumonectomy) and 55 patients (40%) with malignant pleural mesothelioma (extrapleural pneumonectomy). RESULTS: Four perioperative deaths occurred (3%) with no identifiable associated risk factors. Twenty-three patients (17%) had a major complication with an increase in the median length of stay from 7 to 11 days (p < 0.01). Age greater than 65 years, right-sided procedures, and dysrhythmias were associated with an increased risk of a major complication (p < 0.05). Thirty-two patients (24%) had supraventricular dysrhythmias, which occurred on postoperative days 1 to 2 (n = 8), 3 to 4 (n = 13), 5 to 6 (n = 6), and 7 to 12 (n = 5). The median length of stay increased from 8 to 11 days with dysrhythmias (p < 0.05). Factors associated with an increased risk of dysrhythmias included age greater than 65 years, intrapericardial or extrapleural pneumonectomy, right-sided procedure, and any major complication. CONCLUSIONS: Pneumonectomy can be performed safely in selected patients with cancer. Supraventricular dysrhythmia was the most common complication noted with a peak incidence at 3 to 4 days after resection.
Adult↗
Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer.
BACKGROUND: Although complete surgical resection remains the primary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identify, a subset of patients using molecular factors that contribute to tumour aggressiveness, one might improve prognosis in this group with additional treatment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we examined its relation to survival with non-small lung cancer. METHODS: We examined angiogenesis using immunohistochemistry on paraffin blocks of tumour from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration. RESULTS: Measurements in the central area were inconsistent due to prominent necrosis. However, microvessel number recorded at the periphery and at the "hottest" are correlated well (r2 = 0.952; p = 0.001), and a significant survival advantage was noted for low-level expression at both areas (peripheral, p = 0.046; "hottest", p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene p53, and the proliferation marker KI-67 defined angiogenesis as the most significant prognostic factor in stage I lung cancer. CONCLUSIONS: This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of several biologic markers (5-year survival: no marker [n = 51] 81%, 1 marker [n = 82] 71%, 2 markers [n = 84] 54%, and 3 to 4 markers [n = 58] 49%; p = 0.0001).
Adult↗
Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.
OBJECTIVE: The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors. BACKGROUND: Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. METHODS: From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. RESULTS: The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04). CONCLUSIONS: Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.
Combined Modality Therapy↗
Video-assisted thoracic surgery in the elderly. A review of 307 cases.
STUDY OBJECTIVE: The objective of the study was to investigate the impact of video-assisted thoracic surgery (VATS) on age-related morbidity and mortality for thoracic surgical procedures. DESIGN: Prospective data were collected on 896 consecutive VATS procedures from July 1991 to June 1994. Daily in-hospital, postoperative data collection by a full-time thoracic surgical nurse and postdischarge follow-up in a thoracic surgery clinic at 1 and 6 weeks were done. PATIENTS: On 296 patients aged 65 or older, 307 procedures were performed. One hundred nine procedures were performed on patients between 65 and 69 years, 110 on patients between 70 and 74 years, 55 on patients between 75 and 79 years, and 33 on those between 80 and 90 years. MEASUREMENTS AND RESULTS: The population was divided into four cohorts of 5-year age spans for analysis. Comparison was made with Fisher's Exact Test. Overall, 61% of the 307 procedures were for pulmonary disease. There were 32 anatomic lung resections (VATS lobectomies or segmentectomies), 156 extra-anatomic lung resections (thoracoscopic wedge or bullectomy), 78 procedures for pleural disease (25%), 27 mediastinal dissections (9%), and 14 pericardial windows (5%). There was a trend toward a lower mean FEV1 with increasing age. There were 3 deaths; overall mortality was less than 1%. There were 4 conversions to open thoracotomy (1%). Complications occurred with 45 procedures (15% morbidity). Twenty-two operations (7%) were associated with major complications adding to the length of stay and 27 procedures (9%) had minor complications. Median length of stay after VATS was 4 days for patients aged 65 to 79 years and 5 days for those aged 80 to 90 years. Morbidity and mortality were unrelated to age. CONCLUSIONS: The 30-day operative mortality is superior to previous reports of standard thoracotomy. Morbidity is low and length of hospital stay appears improved. VATS techniques may be safer than open thoracotomy in the aged. Age alone should not be a contraindication to operative intervention.
Aged↗
NCCN Non-Small-Cell Lung Cancer Practice Guidelines. The National Comprehensive Cancer Network.
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Carcinoma, Non-Small-Cell Lung↗
Stromelysin-3 is overexpressed by stromal elements in primary non-small cell lung cancers and regulated by retinoic acid in pulmonary fibroblasts.
Stromelysin-3 (STR-3) is a recently characterized matrix metalloproteinase (MMP) that was cloned on the basis of differential expression in benign and malignant breast tumors. This MMP has a unique processing mechanism and substrate specificity. Unlike previously characterized MMPs that are secreted as inactive zymogens, STR-3 is processed within the constitutive secretory pathway and secreted as an active enzyme. Although STR-3 has a characteristic MMP structure, the enzyme does not hydrolyze many of the extracellular matrix components that are substrates for other MMPs. However, STR-3 cleaves certain serine protease inhibitors (serpins), including the alpha 1 proteinase inhibitor (alpha 1 anti-trypsin). Because alpha 1 proteinase inhibitor deficiency has a known pathogenetic role in pulmonary disease, the role of STR-3 in non-small cell lung carcinomas (NSCLC) is of great interest. STR-3 transcripts and protein were significantly more abundant in primary NSCLC than in adjacent normal lung specimens in an extensive panel of stage I-III squamous cell and adenocarcinomas. The major form of STR-3 detectable in the primary NSCLC was the mature fully processed active enzyme. STR-3 transcripts and protein were primarily localized to NSCLC stromal elements, prompting analysis of STR-3 induction in normal pulmonary fibroblasts. Although STR-3 could be induced in normal pulmonary fibroblasts with growth factors (basic fibroblast growth factor and platelet-derived growth factor) and/or 12-O-tetradecanoylphorbol-13-acetate, STR-3 induction was inhibited by all-trans retinoic acid, a commonly used chemopreventive agent for aerodigestive tract malignancies. Taken together, these data suggest that STR-3 may be a novel marker and potential therapeutic target in NSCLC.
Base Sequence↗
Codeletion of p15 and p16 in primary malignant mesothelioma.
The p15 and p16 CDK4 inhibitor genes map within the chromosome band 9p21 region deleted frequently in malignant mesothelioma and other cancers. p16 has been implicated recently as a potential target of 9p21 deletions in mesothelioma, but the role of this gene is uncertain because deletions have been detected more often in established cell lines than in primary tumor specimens. We determined p15 and p16 copy number by fluorescence in situ hybridization with a P1 contig in 50 primary mesotheliomas. Codeletion of p15 and p16 was found in 72% of mesotheliomas, including all cases with spindle-cell components (n = 21) and total deletion of p15 and p16 was found in several mesotheliomas that lacked cytogenetic deletion of the chromosome 9 short arm. Point mutations were not found, however, in exon 2 of retained p15 and p16 alleles from seven mesotheliomas. These findings demonstrate that p15, p16 and/or a closely neighboring gene, are the targets of frequent chromosome 9p deletion in primary malignant mesothelioma.
Base Sequence↗
Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited by p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rb negative. Most NSCLC and SCLC resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16, while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.
Blotting, Southern↗
Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: evidence for a pathogenetic relationship with lipomas and leiomyomas.
Pulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.
Adult↗
Thoracoscopic staging of esophageal cancer: a prospective, multiinstitutional trial. Cancer and Leukemia Group B Thoracic Surgeons.
BACKGROUND: Lymph node metastasis has been shown to be an important prognosticator in esophageal cancer. A prospective, multiinstitutional study of thoracoscopic lymph node staging in patients with biopsy-proven esophageal cancer was undertaken at University of Maryland, Medical University of South Carolina, and Brigham and Women's Hospital. METHODS: Forty-nine patients underwent thoracoscopic staging between September 1991 and August 1993. Five procedures were incomplete due to adhesions. Preoperative computed tomography, magnetic resonance imaging, esophageal ultrasound, and bronchoscopy were performed. After our initial experience with the left side of the chest, thoracoscopic staging was done through the right side of the chest unless specific indications dictated otherwise. Beginning in January 1993 routine laparoscopic/mini-laparotomy lympho node staging of the celiac axis was performed. RESULTS: Satisfactory thoracoscopic lymph node staging was achieved in 44 patients (95%). Of 33 patients undergoing esophageal resection, 29 were correctly staged (88%). Since initiating concomitant laparoscopic lymph node staging, we have correctly staged all of the last 9 patients with regard to celiac lymph nodes as well. Information regarding T status obtained at thoracoscopy was as follows: 3 patients were correctly "downstaged" to T3 despite preoperative noninvasive tests suggesting T4. In 2 patients thoracoscopy correctly predicted T4 invasion, whereas in 2 patients, thoracoscopy missed T4 lesions. CONCLUSIONS: Thoracoscopy is a valuable tool for staging intrathoracic tumors. Preoperative staging of esophageal cancer may allow better allocation of adjuvant therapy. This pilot study suggests that thoracoscopic staging can correctly predict thoracic lymph node status with high accuracy and aid in better defining T status.
Adenocarcinoma↗
Role of nitric oxide in human esophageal circular smooth muscle in vitro.
The role of nitric oxide in human esophageal smooth muscle was examined. Immunostaining for constitutive nitric oxide synthase labeled nerve fibers and bundles within longitudinal and circular smooth muscle layers of resected tissue samples. Strips of circular muscle mounted in organ baths exhibited spontaneous contractions and active tone. When exposed to 5-second trains of electric field stimulation at 20 Hz, most strips exhibited intrastimulus "on" and poststimulus "off" contractions. Exposure to a 0.1 mumol/L (or greater) concentration of atropine converted "on" contractions to "on" relaxations and reduced "off" contractions by 63%. Exposure to NG-nitro-L-arginine resulted in concentration-dependent enhancement of "on" contractions and abolition of "off" contractions. Excess L-arginine enhanced the reversal of these effects. Sodium nitroprusside inhibited both spontaneous and evoked contractions. These results suggest that nitric oxide synthesis is a mediator of neural inhibition of human esophageal circular smooth muscle and is necessary for the occurrence of "off" contractions.
Amino Acid Oxidoreductases↗
Results of cancer and leukemia group B protocol 8935. A multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer. Cancer and Leukemia Group B Thoracic Surgery Group.
From October 1989 to February 1992, 74 patients with mediastinoscopically staged IIIA (N2) non-small-cell lung cancer from 30 CALGB-affiliated hospitals received two cycles of preresectional cisplatin and vinblastine chemotherapy. Patients with responsive or stable disease underwent standardized surgical resection and radical lymphadenectomy. Patients who underwent resection received sequential adjuvant therapy with two cycles of cisplatin and vinblastine, followed by thoracic irradiation (54 Gy after complete resection and 59.4 Gy after incomplete resection or no resection at 1.8 Gy per fraction). There were no radiographic complete responses to the neoadjuvant chemotherapy, although 65 (88%) patients had either a response or no disease progression. During induction chemotherapy, disease progressed in seven patients (9%). Sixty-three patients (86%) had exploratory thoracotomy, and 46 of those (75%) had resectable lesions. A complete surgical resection was accomplished in 23 patients, and 23 patients had an incomplete resection with either a diseased margin or diseased highest node resected. Operative mortality was 3.2% (2/63). In 10 patients (22% of the 46 having resection) the disease was pathologically downstaged. There was no correlation between radiographic response to the induction chemotherapy and downstaging at surgical resection. The full protocol was completed by 33 patients (45% of original cohort). Overall survival at 3 years was 23%. Patients undergoing resection had significantly improved survival at 3 years compared with patients not having resection: 46% for complete resection (median 20.9 months), 25% for incomplete resection (median 17.8 months), and 0% for no resection (median 8.5 months). Five deaths occurred during the treatment period. A total of 18 of the 46 (39%) patients who underwent resection are either alive and disease-free or have died without recurrence.
Aged↗
An historical perspective of multi-modality treatment for resectable non-small cell lung cancer.
We examine the origins of surgical therapy, radiotherapy, and chemotherapy as they were applied to lung cancer in the mid-portion of this century. Surgical therapy for lung cancer started in the 1930s with pneumonectomies. The prognostic significance of nodal metastases was soon recognized, and surgical staging procedures became an important part of patient workup. Radical radiotherapy for potential cure of lung cancer began in the 1950s with megavoltage linear accelerators. The first application of chemotherapy for lung cancer was the use of nitrogen mustards in the 1940s. Single modality surgical therapy has become the treatment of choice for Stages I and II non-small cell lung cancer, but 50% of clinical Stage I patients die of recurrent disease, and 70% of those recur outside the chest. Biologic markers may identify high risk subgroups of Stage I and II patients who may benefit from adjuvant chemo- or radiotherapy. Within the last decade, several single and multi-institutional Phase II trials and two single institution Phase III trials have reported improved survival in Stage IIIA patients treated with cisplatin-based neoadjuvant chemotherapy prior to surgical resection. These trials have reported high response and resectability rates, but at a substantial toxicity. A new standard of care for Stage IIIA disease has not been conclusively established.
Antineoplastic Agents↗
Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.
PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.
Biomarkers↗