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Raphael Bueno

Publications and source records attributed to Raphael Bueno.

At least 19 recordsLinked to original sources
PubMed2006

Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors.

The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to a lesser extent in other solid tumors, is important in understanding epigenetics in carcinogenesis and may be clinically useful for classification of neoplastic disease. Therefore, we investigated whether this putative phenotype exists in exposure-related solid tumors, where somatic gene alterations and enhanced clonal growth are selected for by carcinogens, and examined the ability of methylation profiles to classify malignant disease. We studied promoter hypermethylation of 16 tumor suppressor genes and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous cell carcinomas (HNSCC), 146 non-small-cell lung cancer (NSCLC), and 71 malignant pleural mesotheliomas (MPM). We employed rigorous statistical methods to examine the distribution of promoter methylation and the usefulness of these profiles for disease classification. In bladder cancer, HNSCC, and NSCLC, there was a significant correlation (P < 0.0001) between methylation of the three MINT loci and methylation index, although the distribution of methylated loci varied significantly across these disease. Although there was a significant (P < 0.001) association between gene methylation profile and disease, rates of misclassification of each disease by their methylation profile ranged from 28% to 32%, depending on the classification scheme used. These data suggest that a form of CIMP exists in these solid tumors, although its etiology remains elusive. Whereas the gene profiles of hypermethylation among examined loci could not unequivocally distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation in these cancers suggest that methylation analysis may be clinically useful as a targeted screening tool.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma.

PURPOSE: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. METHODS AND MATERIALS: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m(2)). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. RESULTS: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. CONCLUSIONS: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.

Adult↗
PubMed2006

Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma.

PURPOSE: To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. RESULTS: Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. CONCLUSION: Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.

Aged↗
PubMed2006

Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation.

OBJECTIVE: There is a strong association between reflux and end-stage lung disease, especially idiopathic pulmonary fibrosis. The presence of reflux after lung transplantation might predispose to the development of bronchiolitis obliterans. We evaluated the risk and physiologic effect of laparoscopic fundoplication in patients on the lung transplant waiting list. METHODS: One hundred forty-nine patients on the lung transplant waiting list between March 2001 and January 2005 were evaluated. Nineteen were found to have a history of reflux, continued symptoms, and severe reflux by means of pH and manometric studies and underwent laparoscopic fundoplication. The postoperative course of these 19 patients, including lung function, was retrospectively reviewed. Postoperatively, the lung function of the 14 patients with idiopathic pulmonary fibrosis who underwent the laparoscopic Nissen procedure was compared with that of 31 patients with idiopathic pulmonary fibrosis on the transplant waiting list who did not undergo fundoplication. RESULTS: There were no perioperative complications and no decrease in lung function over the 15-month average follow-up. Exercise capacity remained stable, as determined on the basis of 6-minute walk distance. Patients with idiopathic pulmonary fibrosis treated with fundoplication had stable oxygen requirements, whereas control patients with idiopathic pulmonary fibrosis on the waiting list had a statistically significant deterioration in oxygen requirement. CONCLUSIONS: Laparoscopic fundoplication can be performed safely in patients with end-stage lung disease awaiting lung transplantation. Overall, these patients maintained stable lung function during the follow-up period. When compared with a control group of patients with idiopathic pulmonary fibrosis not undergoing fundoplication, there was stabilization of oxygen requirement. A larger prospective trial evaluating the effect of laparoscopic fundoplication on underlying lung function in this patient population is warranted.

Bronchiolitis Obliterans↗
PubMed2006

Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma.

c-Met receptor tyrosine kinase (RTK) has not been extensively studied in malignant pleural mesothelioma (MPM). In this study, c-Met was overexpressed and activated in most of the mesothelioma cell lines tested. Expression in MPM tissues by immunohistochemistry was increased (82%) in MPM in general compared with normal. c-Met was internalized with its ligand hepatocyte growth factor (HGF) in H28 MPM cells, with robust expression of c-Met. Serum circulating HGF was twice as high in mesothelioma patients as in healthy controls. There was a differential growth response and activation of AKT and extracellular signal-regulated kinase 1/2 in response to HGF for the various cell lines. Dose-dependent inhibition (IC50 < 2.5 micromol/L) of cell growth in mesothelioma cell lines, but not in H2052, H2452, and nonmalignant MeT-5A (IC50 > 10 micromol/L), was observed with the small-molecule c-Met inhibitor SU11274. Furthermore, migration of H28 cells was blocked with both SU11274 and c-Met small interfering RNA. Abrogation of HGF-induced c-Met and downstream signaling was seen in mesothelioma cells. Of the 43 MPM tissues and 7 cell lines, we have identified mutations within the semaphorin domain (N375S, M431V, and N454I), the juxtamembrane domain (T1010I and G1085X), and an alternative spliced product with deletion of the exon 10 of c-Met in some of the samples. Interestingly, we observed that the cell lines H513 and H2596 harboring the T1010I mutation exhibited the most dramatic reduction of cell growth with SU11274 when compared with wild-type H28 and nonmalignant MeT-5A cells. Ultimately, c-Met would be an important target for therapy against MPM.

Aged↗
PubMed2006

Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.

BACKGROUND: A well-known histone deacetylase inhibitor, trichostatin A, was applied to non-small-cell lung cancer cells to determine whether inhibition of histone deacetylase leads to the production of proteins that either arrest tumor cell growth or lead to tumor cell death. METHODS: Trichostatin A (0.01 to 1.0 micromol/L) was applied to one normal lung fibroblast and four non-small-cell lung cancer lines, and its effect was determined by flow cytometry, annexin-V staining, immunoprecipitation, and Western blot analysis. RESULTS: Trichostatin A demonstrated tenfold greater growth inhibition in all four non-small-cell lung cancer lines compared with normal controls, with a concentration producing 50% inhibition ranging from 0.01 to 0.04 micromol/L for the tumor cell lines and 0.7 micromol/L for the normal lung fibroblast line. Trichostatin A treatment reduced the percentage of cells in S phase (10% to 23%) and increased G1 populations (10% to 40%) as determined by flow cytometry. Both annexin-V binding assay and upregulation of the protein, gelsolin (threefold to tenfold), demonstrated that the tumor cells were apoptotic, whereas normal cells were predominantly in cell cycle arrest. Trichostatin A increased histone H4 acetylation and expression of p21 twofold to 15-fold without significant effect on p16, p27, CDK2, and cyclin D1. CONCLUSIONS: Collectively, these data suggest that inhibition of histone deacetylation may provide a valuable approach for lung cancer treatment. We evaluated trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer.

Antineoplastic Agents↗
PubMed2006

Differential diagnosis of solitary lung nodules with gene expression ratios.

OBJECTIVE: We have developed a new technique that uses the ratios of select gene expression levels to translate complex genomic data into simple clinically relevant tests for the diagnosis and prognosis of cancer. We determined whether select gene pair ratio combinations can be used to detect and diagnose lung cancer with high accuracy and sensitivity. METHODS: We used gene expression profiling data to train a ratio-based predictor model to discriminate among a set of samples (n = 145 total) composed of normal lung, small cell lung cancer, adenocarcinoma, squamous cell carcinoma, and pulmonary carcinoid (the training set). We then examined the optimal test in an independent set of samples (the test set, n = 122). Finally, we used one aspect of the test to determine whether the gene ratio technique was capable of detecting cancer in specimens from fine-needle aspirations performed ex vivo with normal lung (n = 14) and suspected tumor nodules (n = 15) acquired at our institution. RESULTS: We found that a ratio-based test with 23 genes could be used to classify training set samples with 90% accuracy. This same test was similarly accurate (88%) when applied to the test set of samples. We also found that this test was 87% and 100% accurate at detecting cancer in normal and tumorous fine-needle aspiration specimens, respectively. CONCLUSION: The gene expression ratio diagnostic technique is likely to aid in the differential diagnosis of solitary lung nodules in patients with suspected cancer and may also prove useful in developing lung cancer screening strategies that incorporate analysis of fine-needle aspiration specimens.

Biopsy, Needle↗
PubMed2005

Validation of genomics-based prognostic tests in malignant pleural mesothelioma.

PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with limited pretreatment prognostication strategies. In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme. EXPERIMENTAL DESIGN: Gene expression data using high-density oligonucleotide microarrays (approximately 22,000 genes) were obtained for a new cohort of human MPM tumors from patients undergoing similar treatments (n = 39). The relative expression levels for specific genes were also determined using real-time quantitative reverse transcription-PCR. We also used a subset of these tumors associated with widely divergent patient survival (n = 23) as a training set to identify new treatment-specific candidate prognostic molecular markers and gene ratio-based prognostic tests. The predictive nature of these newly discovered markers and gene ratio-based prognostic tests were then examined in an independent group of tumors (n = 52) using microarray data and quantitative reverse transcription-PCR. RESULTS: Previously described MPM prognostic genes and gene ratio-based prognostic tests predicted clinical outcome in 39 independent MPM tumor specimens in a statistically significant manner. Newly discovered treatment-specific prognostic genes and gene ratio-based prognostic tests were highly accurate and statistically significant when examined in an independent group of 52 tumors from patients undergoing similar treatment. CONCLUSIONS: The data support the use of gene ratios in translating gene expression data into easily reproducible, statistically validated clinical tests for the prediction of outcome in MPM.

Adult↗
PubMed2005

High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation.

PURPOSE: Lung cancer is the leading cause of cancer mortality in the United States. We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000. PATIENTS AND METHODS: The records of 177 patients were reviewed. Collected data included stage, histology, use of chemotherapy and radiation, initial and subsequent sites of failure, and survival. One hundred twenty-four patients have died; follow-up time is 35 months among the remaining patients. RESULTS: The median survival from the time of surgery was 21.0 months, with a 3-year overall survival (OS) of 34%. Nodal downstaging to N0 disease correlated with OS and progression-free survival (PFS; P < .001). The most common site of recurrence was the brain. Thirty-four percent of patients recurred in the brain as their first site of failure, and 40% of patients developed brain metastases at some point in their course. In patients with nonsquamous histology and residual nodal involvement after neoadjuvant therapy, the risk of brain metastases was 53% at 3 years. CONCLUSION: Patients treated with neoadjuvant therapy for N2-positive stage IIIA NSCLC enjoy an advantage in both OS and PFS if their lymph node status is downstaged to N(0). Because brain metastases constitute the most common site of failure in these patients, future studies focusing on prophylaxis of brain metastases may improve the outcome in patients with stage IIIA NSCLC.

Adult↗
PubMed2005

Antireflux operation for gastroesophageal reflux after Roux-en-y gastric bypass for obesity.

Gastroesophageal reflux disease (GERD) affects many morbidly obese patients. The Roux-en-y gastric bypass operation often achieves the simultaneous aims of weight reduction as well as reflux correction. However, some patients continue to suffer from severe gastroesophageal symptoms after successful postoperative weight reduction. There are no reports describing surgical treatments for these patients. Here we report our management of intractable postoperative reflux with a Belsey Mark IV fundoplication performed one year after a successful Roux-en-y gastric bypass operation. The patient tolerated the operation without problems and experienced successful resolution of her reflux symptoms.

Adult↗
PubMed2005

Multimodality treatments in the management of malignant pleural mesothelioma: an update.

Malignant pleural mesothelioma (MPM) is relatively unique among cancers because the local and regional disease rather than the systemic disease usually contributes to death. Because of its multifocal distribution in the chest, MPM progresses locally by compressing the lung, heart, and major vessels and causes death by cardiac tamponade and lung collapse physiology. The therapy for this aggressive local malignancy is currently inadequate. In most cases there is no sufficient time for systemic disease to develop or contribute to mortality. The first order of therapy in MPM is currently, as it has been for decades, to control effectively the tumor's locoregional spread and then deal with controlling the distant disease.

Combined Modality Therapy↗
PubMed2005

Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.

Blotting, Western↗
PubMed2005

Lung resection in patients with preoperative FEV1 < 35% predicted.

OBJECTIVES: To determine the morbidity, mortality, and feasibility of lung resection in patients with tumors and preoperative FEV1 < 35% predicted. DESIGN: Retrospective review. SETTING: A 734-bed, tertiary care, academic hospital with a dedicated general thoracic surgery unit performing > 2,000 operations per year. PATIENTS: One hundred consecutive patients with discrete lung tumors and with preoperative FEV1 < 35% predicted undergoing lung resection between September 1997 and May 2003. Only operations with curative intent were included. Average preoperative predicted FEV1 was 26%. Sixteen percent of the patients were oxygen dependent prior to the operation. RESULTS: Open and thoracoscopic wedge resections, segmentectomies, lobectomies, and combined lung resections with lung volume reduction were performed. Sixty-six of the lesions were malignant, and 57 were primary lung cancers. Only one patient left the operating room with positive margins. There was one in-hospital or 30-day mortality. Thirty-six percent of the patients had one or more complications. Twenty-two percent of the patients had prolonged air leaks requiring a chest tube for > 7 days. One patient left the hospital ventilator dependent, 3 additional patients required intubation > 48 h, and 11 patients were discharged with a new oxygen requirement. There were four pneumonias, one myocardial infarction, and two reoperations for bleeding. Male gender (p = 0.003), preoperative oxygen dependence (p = 0.03), and pack-year history (p = 0.006) were associated with a higher overall incidence of complications, while age, incision, diabetes, coronary artery disease, duration of smoking cessation, amount of lung resected, size of lesion, and preoperative percentage of predicted FEV1 did not correlate with the overall incidence of complications. CONCLUSIONS: In a large academic center, minimally invasive surgical techniques, intensive pulmonary care, and advanced anesthetic techniques allow for curative lung tumor resections in patients with very low preoperative FEV1 with a very low mortality and very low incidence of ventilator dependence. Other serious complications such as pneumonia, myocardial infarction, and bleeding are uncommon. An extended hospital stay and a high incidence of prolonged air leak should be expected, especially in patients with preoperative FEV1 < or = 20% predicted.

Adult↗
PubMed2005

Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database.

STUDY OBJECTIVES: To determine the effect of age and type of surgery on long-term survival in patients with early-stage non-small cell lung cancer (NSCLC). DESIGN AND PATIENTS: A total of 14,555 patients who were > or = 20 years of age with stage I or II primary NSCLC and had been registered in the Surveillance, Epidemiology, and End Results Database from 1992 to 1997 were analyzed. Age was grouped into the following three categories: < 65 years (n = 5,057; 35%); 65 to 74 years (n = 6,073; 42%); and > or = 75 years (n = 3,425; 23%). Log-rank tests and Cox regression models were used for crude and adjusted survival analyses. MEASUREMENTS AND RESULTS: A total of 8,080 men (55%) and 6,475 women (mean [+/- SD] age, 67.3 +/- 9.8 years) with stage I NSCLC (83%) or stage II NSCLC were analyzed. Curative surgery was performed in 4,669 patients (92%) who were < 65 years of age (youngest), 5,219 patients (86%) who were 65 to 74 years of age (intermediate age), and 2,382 patients (70%) who were > or = 75 years of age (elderly) [p < 0.0001]. Thirty percent of the elderly patients were denied surgery or were offered only palliative surgery, in contrast with 8% among the youngest patients (p < 0.0001). Limited resections increased from 8% in young patients to 17% in the elderly (p < 0.0001). Survival decreased with age. The median survival times were 71, 47, and 28 months, respectively, for patients < 65, 65 to 74, and > or = 75 years of age (p < 0.0001). The results were unchanged after adjusting for sex, type of surgery, histology, and stage of disease. For the young patients, lobectomies conferred better survival times than limited resections after 2 years. However, there was no difference in survival between lobectomies and limited resections in terms of survival time for the elderly patients. The statistical difference in long-term survival between those patients undergoing lobectomies and those undergoing limited resections disappeared at 71 years. CONCLUSIONS: Age is an independent predictor of postsurgical survival in NSCLC patients, even after adjustment for significant covariates. Curative surgery is performed less frequently in elderly patients. Among younger patients undergoing curative surgery, lobectomies are more commonly performed and confer a significant survival benefit over limited resections. This benefit, however, is not evident for patients > 71 years of age.

Aged↗
PubMed2005

Diameter of non-small cell lung cancer correlates with long-term survival: implications for T stage.

STUDY OBJECTIVES: To determine the effect of tumor diameter on the long-term survival of patients with stage I non-small cell lung cancer (NSCLC) within a large multi-institutional database, and to assess the accuracy of the T-descriptor threshold of 3 cm. DESIGN AND PATIENTS: A total of 9,191 patients > or = 20 years old with surgically treated stage I NSCLC < or = 6 cm registered in the Surveillance, Epidemiology, and End Results database from 1992 to 1997 were included. The size of the nodule was grouped into six categories: < 1 cm (n = 191, 2%), 1 to 1.9 cm (n = 2,130, 23%), 2 to 2.9 cm (n = 2,851, 31%), 3 to 3.9 cm (n = 1,984, 22%), 4 to 4.9 cm (n = 1,161, 13%), and 5 to 6 cm (n = 874, 9%). Due to its limited sample size, subcentimeter nodules were not included in the survival analysis. Survival analyses were performed with Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards models. MEASUREMENTS AND RESULTS: A total of 4,904 (53%) men and 4,287 women (mean +/- SD age, 66.6 +/- 9.4 years) with stage I NSCLC were analyzed. The use of lobectomies and pneumonectomies as surgical treatment instead of limited resections increased with the size of the tumor, from 62% in subcentimeter nodules to 96% in 5- to 6-cm tumors (p < 0.0001). Survival decreased with increasing size of the tumor (p < 0.0001). There was a significant survival difference when size groups were compared to tumors 1.0 to 1.9 cm: 2.0 to 2.9 cm (hazard ratio [HR], 1.3; 95% confidence interval [CI], 1.16 to 1.47), 3.0 to 3.9 cm (HR, 1.49; 95% CI, 1.32 to 1.69), 4.0 to 4.9 cm (HR, 1.82; 95% CI, 1.59 to 2.08), and 5.0 to 6.0 cm (HR, 2.04; 95% CI, 1.77 to 2.36). Survival was similar in tumors between 2.0 to 2.9 cm and 3.0 to 3.9 cm, and in tumors between 4.0 to 4.9 cm and 5.0 to 6.0 cm. CONCLUSIONS: The T descriptor should be changed so that T1 is reserved for tumors < 2 cm. Further refinement of larger tumors into T2a (2 to 3.9 cm) and T2b (> or = 4 cm) should be considered.

Adenocarcinoma↗