Search tips
Search criteria

Results 1-21 (21)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
1.  Symptom recovery after thoracic surgery: measuring patient-reported outcomes with the MD Anderson Symptom Inventory 
Measuring patient-reported outcomes (PROs) has become increasingly important for assessing quality of care and guiding patient management. However, PROs have yet to be integrated with traditional clinical outcomes (such as length of hospital stay) to evaluate perioperative care. This study aimed to utilize longitudinal PRO assessments to define the postoperative symptom-recovery trajectory in patients undergoing thoracic surgery for lung cancer.
Newly diagnosed patients (N=60) with stage I or II non-small cell lung cancer who underwent either standard open thoracotomy or video-assisted thoracoscopic surgery (VATS) lobectomy reported multiple symptoms from presurgery to 3 months postsurgery using the MD Anderson Symptom Inventory (MDASI). We conducted Kaplan–Meier analyses to determine when symptoms returned to presurgical levels and to mild severity levels during recovery.
The most-severe postoperative symptoms were fatigue, pain, shortness of breath, disturbed sleep, and drowsiness. The median time to return to mild symptom severity for these 5 symptoms was shorter than return to baseline severity, with fatigue taking longer. Pain recovered more quickly for patients who underwent VATS lobectomy vs standard open thoracotomy (8 days vs 18 days, respectively; P = .022). Patients who had poor preoperative performance status or comorbidities reported higher postoperative pain (all P < .05).
Assessing symptoms from the patient's perspective throughout the postoperative recovery period is an effective strategy for evaluating perioperative care. This study demonstrates that the MDASI is a sensitive tool for detecting symptomatic recovery with an expected relationship among surgery type, preoperative performance status, and comorbid conditions.
PMCID: PMC4554973  PMID: 26088408
patient-reported outcome (PRO); MDASI; postoperative care; VATS; symptoms; enhanced recovery
3.  Gene mutations in primary tumors and corresponding patient-derived xenografts derived from non-small cell lung cancer 
Cancer letters  2014;357(1):179-185.
Molecular annotated patient-derived xenograft (PDX) models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. We established 23 PDXs from 88 surgical specimens of lung cancer patients and determined gene mutations in these PDXs and their paired primary tumors by ultradeep exome sequencing on 202 cancer-related genes. The numbers of primary tumors with deleterious mutations in TP53, KRAS, PI3KCA, ALK, STK11, and EGFR were 43.5%, 21.7%, 17.4%, 17.4%, 13.0%, and 8.7%, respectively. Other genes with deleterious mutations in ≥3 (13.0%) primary tumors were MLL3, SETD2, ATM, ARID1A, CRIPAK, HGF, BAI3, EP300, KDR, PDGRRA and RUNX1. Of 315 mutations detected in the primary tumors, 293 (93%) were also detected in their corresponding PDXs, indicating that PDXs have the capacity to recapitulate the mutations in primary tumors. Nevertheless, a substantial number of mutations had higher allele frequencies in the PDXs than in the primary tumors, or were not detectable in the primary tumor, suggesting the possibility of tumor cell enrichment in PDXs or heterogeneity in the primary tumors. The molecularly annotated PDXs generated from this study could be useful for future translational studies.
PMCID: PMC4301580  PMID: 25444907
Lung cancer; Gene mutations; Tumor models; Patient-derived xenografts; Biomarkers
4.  Telomere length and recurrence risk after curative resection in patients with early-stage non-small cell lung cancer: a prospective cohort study 
We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non-small cell lung cancer (NSCLC).
This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative resection at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time PCR. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model.
Median duration of follow-up was 61 months and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared to those without recurrence (1.13 vs 1.07, P=0.046). A subgroup analysis indicates that women had longer RTL compared to males (1.12 vs 1.06, P=0.025), and the patients with adenocarcinoma demonstrated longer RTL compared to those with other histologic types (1.11 vs 1.05, P=0.042). To determine if longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, gender, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in female (HR=2.25; 95% CI, 1.02-4.96, P=0.044) and adenocarcinoma subgroups (HR=2.19; 95% CI, 1.05-4.55, P=0.036). The increased risk of recurrence due to long RTL was more apparent in females with adenocarcinoma (HR=2.67; 95% CI, 1.19-6.03, P=0.018).
This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma appear to be special subgroups in which telomere biology may play an important role.
PMCID: PMC4305022  PMID: 25299235
5.  Genetic variation in the TNF/TRAF2/ASK1/p38 kinase signaling pathway as markers for postoperative pulmonary complications in lung cancer patients 
Scientific Reports  2015;5:12068.
Post-operative pulmonary complications are the most common morbidity associated with lung resection in non-small cell lung cancer (NSCLC) patients. The TNF/TRAF2/ASK1/p38 kinase pathway is activated by stress stimuli and inflammatory signals. We hypothesized that genetic polymorphisms within this pathway may contribute to risk of complications. In this case-only study, we genotyped 173 germline genetic variants in a discovery population of 264 NSCLC patients who underwent a lobectomy followed by genotyping of the top variants in a replication population of 264 patients. Complications data was obtained from a prospective database at MD Anderson. MAP2K4:rs12452497 was significantly associated with a decreased risk in both phases, resulting in a 40% reduction in the pooled population (95% CI:0.43–0.83, P = 0.0018). In total, seven variants were significant for risk in the pooled analysis. Gene-based analysis supported the involvement of TRAF2, MAP2K4, and MAP3K5 as mediating complications risk and a highly significant trend was identified between the number of risk genotypes and complications risk (P = 1.63 × 10−8). An inverse relationship was observed between association with clinical outcomes and complications for two variants. These results implicate the TNF/TRAF2/ASK1/p38 kinase pathway in modulating risk of pulmonary complications following lobectomy and may be useful biomarkers to identify patients at high risk.
PMCID: PMC4499815  PMID: 26165383
6.  Preoperative chemotherapy prior to pulmonary metastasectomy in surgically resected primary colorectal carcinoma 
Oncotarget  2014;5(16):6584-6593.
The benefit of preoperative chemotherapy prior to pulmonary metastasectomy for patients with colorectal carcinoma (CRC) is unknown. Here, we identify outcomes of preoperative chemotherapy in patients with resected primary CRC who then underwent pulmonary metastasectomy.
We queried a prospective database to identify treatment characteristics. Multivariate analyses identified predictors of overall survival (OS) and progression-free survival (PFS).
229 patients underwent lung metastasectomy, of whom 115 proceeded to surgery without chemotherapy while 114 received preoperative regimen based on oxaliplatin (32%), irinotecan (46%), capecitabine (16%), or other (6%). Median PFS in preoperative chemotherapy vs. surgery alone arms were comparable (p=0.004). Patients on oxaliplatin-based therapy had an improved OS vs. an irinotecan, capecitabine, or alternate regimen (p=.019). On multivariate analysis, the irinotecan subset had a worse OS (HR 1.846; 95% CI 1.070, 3.185) vs. surgery alone arm (p=0.028). The OS of an oxaliplatin-based regimen vs. no chemotherapy was inconclusive (HR 0.57; 95% CI 0.237 to 1.389, p=0.218). Multivariate analysis demonstrated a worse PFS and OS for the male gender and an incomplete resection (R2).
Prospective trials on specific preoperative regimens and criteria for patient selection may identify a role for preoperative chemotherapy prior to a curative pulmonary metastasectomy.
PMCID: PMC4196147  PMID: 25051371
colorectal; carcinoma; neoadjuvant; chemotherapy; metastasectomy
7.  Does the Timing of Esophagectomy after Neoadjuvant Chemoradiation Affect Outcome? 
The Annals of thoracic surgery  2011;93(1):207-213.
After neoadjuvant chemoradiation (CXRT) for esophageal cancer, surgery has traditionally been recommended to be performed within 8 weeks. However, surgery is often delayed for various reasons. Data from other cancers suggests that delaying surgery may increase the pathologic complete response rate. However, there are theoretical concerns that waiting longer after radiation may lead to a more difficult operation and more complications. The optimal timing of esophagectomy after CXRT is unknown.
From a prospective database, we analyzed 266 patients with resected esophageal cancer who were treated with neoadjuvant CXRT from 2002–2008. Salvage resections were excluded from this analysis. We compared patients who had surgery within 8 weeks of CXRT and those who had surgery after 8 weeks. We used multivariable analysis to determine whether increased interval between chemoradiation and surgery was independently associated with perioperative complication, pathologic response, or overall survival.
150 patients were resected within 8 weeks and 116 were resected greater than 8 weeks after completing CXRT. Mean length of operation, intraoperative blood loss, anastomotic leak rate, and perioperative complication rate were similar for the two groups. Pathologic complete response rate and overall survival were also similar for the two groups (p=NS). In multivariable analysis, timing of surgery was not an independent predictor of perioperative complication, pathologic complete response, or overall survival.
The timing of esophagectomy after neoadjuvant CXRT is not associated with perioperative complication, pathologic response, or overall survival. It may be reasonable to delay esophagectomy beyond 8 weeks for patients who have not yet recovered from chemoradiation.
PMCID: PMC4041623  PMID: 21962263
Adjuvant/neoadjuvant therapy; Esophageal Cancer; Radiation Therapy; Esophageal Surgery
8.  Outcome of Trimodality-Eligible Esophagogastric Cancer Patients Who Declined Surgery after Preoperative Chemoradiation 
Oncology  2012;83(5):10.1159/000341353.
For patients with localized esophageal cancer (EC) who can withstand surgery, the preferred therapy is chemoradiation followed by surgery (trimodality). However, after achieving a clinical complete response [clinCR; defined as both post-chemoradiation endoscopic biopsy showing no cancer and physiologic uptake by positron emission tomography (PET)], some patients decline surgery. The literature on the outcome of such patients is sparse.
Between 2002 and 2011, we identified 622 trimodality-eligible EC patients in our prospectively maintained databases. All patients had to be trimodality eligible and must have completed preoperative staging after chemoradiation that included repeat endoscopic biopsy and PET among other routine tests.
Out of 622 trimodality-eligible patients identified, 61 patients (9.8%) declined surgery. All 61 patients had a clinCR. The median age was 69 years (range 47–85). Males (85.2%) and Caucasians (88.5%) were dominant. Baseline stage was II (44.2%) or III (52.5%), and histology was adenocarcinoma (65.6%) or squamous cell carcinoma (29.5%). Forty-two patients are alive at a median follow-up of 50.9 months (95% CI 39.5–62.3). The 5-year overall and relapse-free survival rates were 58.1 ± 8.4 and 35.3 ± 7.6%, respectively. Of 13 patients with local recurrence during surveil-lance, 12 had successful salvage resection.
Although the outcome of 61 EC patients with clinCR who declined surgery appears reasonable, in the absence of a validated prediction/prognosis model, surgery must be encouraged for all trimodality-eligible patients.
PMCID: PMC3832345  PMID: 22964903
Esophageal cancer; Trimodality; Surgery; Chemoradiation; Outcomes
9.  Perioperative blood transfusions and survival in patients with non-small cell lung cancer: a retrospective study 
BMC Anesthesiology  2013;13:42.
Perioperative blood transfusions have been associated with poor clinical outcomes in the context of oncological surgery. Current literature is inconclusive whether blood transfusions are linked to shorter recurrence free and overall survival after lung cancer surgery. We hypothesize that blood transfusions in patients undergoing surgery for non-small cell lung cancer are associated with poor oncological survival.
After IRB approval, perioperative data from 636 patients who underwent lung cancer surgery was collected. Patients were evaluated for time to tumor recurrence and overall survival.
60 patients were transfused and 576 subjects were not. Patients who received transfusion were more likely to have more advanced disease (p = 0.018), and preoperative low hemoglobin concentrations (p < 0.0001) compared to non-transfused patients. In the multivariable Cox regression analysis, blood transfusion was associated with a significant reduction in recurrence free survival (p = 0.025), HR: 1.55 (95% CI: 1.06-2.27) and overall survival (p = 0.0002) HR: 2.04 (95% CI: 1.41-2.97). However, analysis after propensity score matching between the two groups revealed that the effect of blood transfusion was significant for reduction in overall survival (p = 0.0356), HR: 1.838 (95% CI: 1.04-3.22) but not for recurrence free survival (p = 0.1460), HR: 1.493 (95% CI: 0.87-2.56).
Perioperative administration of red blood cells appears be associated with a decreased overall survival but not recurrence free survival after lung cancer surgery. Our study has the limitations of a retrospective review. Hence, our results should be confirmed by a prospective randomized control trial.
PMCID: PMC3832885  PMID: 24228905
10.  Genetic Variations in Epigenetic Genes Are Predictors of Recurrence in Stage I or II Non–Small Cell Lung Cancer Patients 
Clinical Cancer Research  2012;18(2):585-592.
Early-stage non–small cell lung cancer (NSCLC) is potentially curable, however, many patients develop recurrent disease. Therefore, identification of biomarkers that can be used to predict patient’s risk of recurrence and survival is critical. Genetic polymorphisms or single-nucleotide polymorphisms (SNP) of DNA- and histone-modifying genes, particularly those of O6-methylguanine DNA-methyltransferase (MGMT), have been linked to an increased risk of lung cancer as well as treatment outcomes in other tumors.
Experimental Design
We assessed the association of 165 SNPs in selected epigenetic enzyme genes, DNA methyltransferases, and methyl-CpG–binding proteins with cancer recurrence in 467 patients with stage I or II NSCLC treated with either surgery alone (N = 340) or surgery plus (neo)-adjuvant chemotherapy (N = 127).
We found several SNPs to be strongly correlated with tumor recurrence. We identified 10 SNPs that correlated with the outcome in patients treated with surgery alone but not in patients treated with surgery and adjuvant chemotherapy, which suggested that the addition of platinum-based chemotherapy could reverse the high genetic risk of recurrence. We also identified 10 SNPs that predicted the risk of recurrence in patients treated with surgery plus adjuvant chemotherapy but not in patients treated with surgery alone. The cumulative effect of these SNPs significantly predicted outcomes with P-values of 10−9and 10−6, respectively.
The first set of genotypes may be used as novel predictive biomarkers to identify patients with stage I NSCLC, who could benefit from adjuvant chemotherapy, and the second set of SNPs might predict response to adjuvant chemotherapy.
PMCID: PMC3373176  PMID: 22252258
11.  Predictors for Locoregional Recurrence for Clinical Stage III-N2 Non-small Cell Lung Cancer with Nodal Downstaging After Induction Chemotherapy and Surgery 
Annals of Surgical Oncology  2012;20(6):1934-1940.
Pathologic downstaging following chemotherapy for stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown.
Between 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery. All had pathologic N0-1 disease, and none received postoperative radiotherapy. LRR were defined as recurrence at the surgical site, lymph nodes (levels 1–14 including supraclavicular), or both.
Median follow-up was 39.3 months. Pretreatment N2 status was confirmed pathologically (18.2 %) or by PET/CT (81.8 %). Overall, the 5-year LRR rate was 30.8 % (n = 38), with LRR being the first site of failure in 51 % (22/+99877943). Five-year overall survival for patients with LRR compared with those without was 21 versus 60.1 % (p < 0.001). Using multivariate analysis, significant predictors for LRR were pN1 disease at time of surgery (p < 0.001, HR 3.43, 95 % CI 1.80–6.56) and a trend for squamous histology (p = 0.072, HR 1.93, 95 % CI 0.94–3.98). Five-year LRR rate for pN1 versus pN0 disease was 62 versus 20 %. Neither single versus multistation N2 disease (p = 0.291) nor initial staging technique (p = 0.306) were predictors for LRR. N1 status also was predictive for higher distant recurrence (p = 0.021, HR 1.91, 95 % CI 1.1–3.3) but only trended for poorer survival (p = 0.123, HR 1.48, 95 % CI 0.9–2.44).
LRR remains high in resected stage III-N2 NSCLC patients after induction chemotherapy and nodal downstaging, particularly in patients with persistent N1 disease.
Electronic supplementary material
The online version of this article (doi:10.1245/s10434-012-2800-x) contains supplementary material, which is available to authorized users.
PMCID: PMC3656229  PMID: 23263700
12.  The Role of Consolidation Therapy for Stage III Non-Small Cell Lung Cancer With Persistent N2 Disease After Induction Chemotherapy 
The Annals of thoracic surgery  2012;94(3):914-920.
Persistent pathologic mediastinal nodal involvement after induction chemotherapy and surgical resection is a negative prognostic factor for stage III-N2 non-small cell lung cancer patients. This population has high rates of local-regional failure and distant failure, yet the effectiveness of additional therapies is not clear. We assessed the role of consolidative therapies (postoperative radiation therapy and chemotherapy) for such patients.
In all, 179 patients with stage III-N2 non-small cell lung cancer at MD Anderson Cancer Center were treated with induction chemotherapy followed by surgery from 1998 through 2008; 61 patients in this cohort had persistent, pathologically confirmed, mediastinal nodal disease, and were treated with postoperative radiation therapy. Local-regional failure was defined as recurrence at the surgical site or lymph nodes (levels 1 to 14, including supraclavicular), or both. Overall survival was calculated using the Kaplan-Meier method, and survival outcomes were assessed by log rank tests. Univariate and multivariate Cox proportional hazards models were used to identify factors influencing local-regional failure, distant failure, and overall survival.
All patients received postoperative radiation therapy after surgery, but approximately 25% of the patients also received additional chemotherapy: 9 (15%) with concurrent chemotherapy, 4 (7%) received adjuvant sequential chemotherapy, and 2 (3%) received both. Multivariate analysis indicated that additional postoperative chemotherapy significantly reduced distant failure (hazard ratio 0.183, 95% confidence interval: 0.052 to 0.649, p = 0.009) and improved overall survival (hazard ratio 0.233, 95% confidence interval: 0.089 to 0.612, p = 0.003). However, additional postoperative chemotherapy had no affect on local-regional failure.
Aggressive consolidative therapies may improve outcomes for patients with persistent N2 disease after induction chemotherapy and surgery.
PMCID: PMC3468148  PMID: 22819472
13.  Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy 
We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) treated with or without neoadjuvant chemotherapy.
Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed.
The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ≤10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001).
The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies.
PMCID: PMC3465940  PMID: 22481232
Lung cancer; Neoadjuvant chemotherapy; Histopathology
14.  Variations in the Vascular Endothelial Growth Factor Pathway Predict Pulmonary Complications 
The Annals of thoracic surgery  2012;94(4):1079-1085.
Clinical factors predicting pulmonary complications after lung resection have been well described, whereas the role of genetics is unknown. The vascular endothelial growth factor (VEGF) signaling pathway has been linked to acute lung injury. We hypothesized that genetic variations in this pathway may be associated with postoperative pulmonary complications after lung resection.
One hundred ninety-six single nucleotide polymorphisms (SNPs) in 17 genes in the VEGF pathway were genotyped in a discovery set of 264 patients and a replication set of 264 patients who underwent lobectomy for lung cancer. Multivariable analysis adjusting for baseline clinical factors was used to identify SNPs associated with pulmonary complications. Cumulative and classification and regression tree (CART) analyses were used to further stratify risk groups.
The overall number of pulmonary complications was 164/528 (31%). The effects of 6 SNPs were consistent in the discovery and replication sets (pooled p value < 0.05). The rs9319425 SNP in the VEGF receptor gene FLT1 resulted in a 1.50-fold increased risk (1.15–1.96; p = 0.003). A cumulative effect for the number of risk genotypes and complications was also evident (p < 0.01). Patients carrying 5 risk genotypes had a 5.76-fold increase in risk (2.73–12.16; p = 4.44 × 10−6). Regression tree analysis identified potential gene-gene interactions between FLT1:rs9319425 and RAF1:rs713178. The addition of the 6 SNPs to the clinical model increased the area under the receiver operating characteristic curve by 6.8%.
Genetic variations in the VEGF pathway are associated with risk of pulmonary complications after lobectomy. This may offer insight into the underlying biological mechanisms of pulmonary complications.
PMCID: PMC3466075  PMID: 22795057
15.  Prognostic Significance of Ataxia-Telangiectasia Mutated, DNA-dependent Protein Kinase Catalytic Subunit, and Ku Heterodimeric Regulatory Complex 86-kD Subunit Expression in Patients With Nonsmall Cell Lung Cancer 
Cancer  2008;112(12):2756-2764.
The double-strand break (DSB) repair capacity has been implicated in the survival of patients in several cancer types. However, little is known about the prognostic importance of the key DSB repair genes—ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the Ku heterodimeric regulatory complex 86-kD subunit (Ku80)—in nonsmall cell lung cancer (NSCLC). To address this issue, the authors determined the messenger RNA (mRNA) expression of these genes in patients NSCLC and assessed their prognostic relevance.
mRNA expression levels of ATM, DNA-PKcs, and Ku80 were measured in tumor and adjacent normal tissues from 140 patients with NSCLC by using quantitative real-time polymerase chain reaction analysis. Then, a Cox proportional hazards regression model and Kaplan-Meier plots were used to evaluate the association between the tumor:normal (T/N) expression ratios of the 3 genes and the overall survival rate and duration in patients with NSCLC.
mRNA expression of ATM and DNA-PKcs, but not of Ku80, was significantly higher in tumor tissues than in adjacent normal tissues (P = .003 and P < .001, respectively). The high T/N expression ratios of ATM and DNA-PKcs were associated significantly with a 1.82-fold increased risk of death (95% confidence interval, 1.05–2.70) and a 2.13-fold increased risk of death (95% confidence interval, 1.21–3.76), respectively. However, no significant association with risk was observed for Ku80. Kaplan-Meier analyses revealed that patients with high T/N expression ratios of ATM or DNA-PKcs had notably shorter median survival than patients with low ratios.
The current findings suggested that the T/N expression ratios of ATM and DNA-PKcs may be useful for identifying NSCLC patients with a poor prognosis who may benefit from more aggressive therapy.
PMCID: PMC3384998  PMID: 18457328
DNA repair; DNA double-strand break; nonsmall cell lung cancer; prognosis
16.  Automated detection of genetic abnormalities combined with cytology in sputum is a sensitive predictor of lung cancer 
Modern Pathology  2008;21(8):950-960.
Detection of lung cancer by sputum cytology has low sensitivity but is noninvasive and, if improved, could be a powerful tool for early lung cancer detection. To evaluate whether the accuracy of diagnosing lung cancer by evaluating sputa for cytologic atypia and genetic abnormalities is greater than that of conventional cytology alone, automated scoring of genetic abnormalities for 3p22.1 and 10q22.3 (SP-A) by fluorescence in situ hybridization (FISH) and conventional cytology was done on sputa from 35 subjects with lung cancer, 25 high-risk smokers, and 6 healthy control subjects. Multivariate analysis was performed to select variables that most accurately predicted lung cancer. A model of probability for the presence of lung cancer was derived for each subject. Cells exfoliated from patients with lung cancer contained genetic aberrations and cytologic atypias at significantly higher levels than in those from control subjects. When combined with cytologic atypia, a model of risk for lung cancer was derived that had 74% sensitivity and 82% specificity to predict the presence of lung cancer, whereas conventional cytology achieved only 37% sensitivity and 87% specificity. For diagnosing lung cancer in sputum, a combination of molecular and cytologic variables was superior to using conventional cytology alone.
PMCID: PMC3377448  PMID: 18500269
surfactant protein A gene; 3p22.1; FISH; cytology; field cancerization effect; sputum
17.  3p22.1 and 10q22.3 Deletions Detected by Fluorescence In Situ Hybridization (FISH) 
Journal of Thoracic Oncology  2008;3(9):979-984.
Our objective was to study the feasibility of detecting chromosomal deletions at 3p22.1 and 10q22.3 by fluorescent in situ hybridization (FISH) and to examine their distribution in different areas of the airway in patients with non-small cell lung cancer.
Brush biopsies from the mainstem bronchus on the normal side contralateral to the tumor (NBB) and mainstem bronchus on the tumor side (TBB) were obtained from 122 patients who underwent surgical resection. Touch preparations from the tumor (TTP), normal lung parenchyma, and bronchi adjacent to the tumor were also obtained. Two FISH assays using probes complementary to 3p22.1 and 10q22.3 were used to detect deletions.
NBB showed a relatively low deletion rate of 3p22.1 and 10q22.3 compared with TTP (p < 0.0001). TBB showed a significantly higher rate of deletions compared with NBB but lower than TTP from the tumor (p < 0.05) for both 3p22.1 and 10q22.3. A significantly higher deletion rate was seen at TTP compared with normal lung parenchyma at both the 3p22.1 and 10 q22.3 (p < 0.0001). Correlations were seen between the deletion rates of TTP and TBB at 3p22.1 (ρ = 0.61, p < 0.0001) and between TTP and bronchi adjacent to the tumor at 10q22.3 (ρ = 0.64, p < 0.0001).
Deletions of the 3p22.1 and 10q22.3 regions can be reliably detected by FISH. As one progresses from the contralateral normal bronchus to the bronchus on the side of tumor and the tumor itself, the percentage of chromosomal deletions increases in a statistically significant fashion. This suggests that, FISH analysis of bronchoscopic brushes may be useful for identifying patients at high risk for developing non-small cell lung cancer.
PMCID: PMC3370669  PMID: 18758299
Lung; Cancer; Non-small cell; Screening; Fluorescent in situ hybridization; Bronchial brushes
18.  Automated Symptom Alerts Reduce Postoperative Symptom Severity After Cancer Surgery: A Randomized Controlled Clinical Trial 
Journal of Clinical Oncology  2011;29(8):994-1000.
Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery. This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control.
Patients and Methods
We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm randomized controlled trial; 79 patients completed the study. After hospital discharge, patients rated symptoms twice weekly for 4 weeks via automated telephone calls. For intervention group patients, an e-mail alert was forwarded to the patient's clinical team for response if any of a subset of symptoms (pain, disturbed sleep, distress, shortness of breath, or constipation) reached a predetermined severity threshold. No alerts were generated for controls. Group differences in symptom threshold events were examined by generalized estimating equation modeling.
The intervention group experienced greater reduction in symptom threshold events than did controls (19% v 8%, respectively) and a more rapid decline in symptom threshold events. The difference in average reduction in symptom interference between groups was −0.36 (SE, 0.078; P = .02). Clinicians responded to 84% of e-mail alerts. Both groups reported equally high satisfaction with the automated system and with postoperative symptom control.
Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery. Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery. These results should be confirmed in a larger study.
PMCID: PMC3068055  PMID: 21282546
19.  The Influence of Pretreatment Body Mass Index on Long-Term Prognosis of Patients With Esophageal Carcinoma After Surgery 
Obesity, which is one of the most serious health problems in United States, is considered a risk factor for lower esophageal and gastric cardia adenocarcinoma. However, the influence of obesity on esophageal cancer survival has not been determined. The aim of this study is to examine the impact of obesity on the long-term mortality outcomes for patients with esophageal cancer after surgery.
A retrospective review was performed of 243 consecutive esophageal cancer patients undergoing surgery who did not receive neoadjuvant therapy. Patients were grouped according to pretreatment body mass index, as normal/underweight (<25 kg/m2) and overweight (≥25 kg/m2). Overall and recurrence-free survivals were investigated using Kaplan-Meier method, and Cox regression model was used to determine the significant prognostic factors on univariate and multivariate analysis.
There were 67 patients (28%) who were classified as normal/underweight and 176 patients (72%) as overweight. In the overweight group, the numbers of patients who were male (P < .001), with adenocarcinoma (P < .001), and pathologic stage I (p=0.003) were significantly higher than in the normal/underweight group. There was no significant difference in postoperative morbidity rates between the two groups. Both local/regional and distant recurrence rates were significantly higher in the normal/underweight group (P = .027 and P = .039, respectively). The 5-year overall survival rates were 41% in the normal/underweight group, and 67% in the overweight group (P = .002). The 5-year disease free survival rates were 37% in the normal/underweight group, and 65% in the overweight group (P = .001). In univariate analysis, BMI ≥25 and lower esophagus tumor were factors associated with longer survival. Factors including older age, weight loss before treatment, smoking history, squamous cell carcinoma, tumor size>3 cm, pathologic stage III, and poorly differentiated carcinoma were significantly associated with shorter patient survival. In multivariate analysis, age, pathologic stage and tumor location ultimately remained as prognostic factors. Lower esophageal tumor (P = .015; HR, 0.386; 95% CI, 0.179–0.833) was related with better survival, and older age (P = .014; HR, 1.032; 95% CI, 1.006–1.057) and stage III disease (P = .015; HR, 6.162; 95% CI, 1.744–21.766) were related with poor survival.
Pretreatment BMI cannot be recognized as an independent predictor of long-term prognosis in esophageal cancer patients after surgery. However, high BMI tends to be associated with better prognosis.
This work was supported in part by grants from UT M. D. Anderson Cancer Center, Dallas, Park, Cantu, Smith, and Myers families and by the River Creek Foundation.
PMCID: PMC3056311
20.  Application of the revised lung cancer staging system (IASLC Staging Project) to a cancer center population 
The International Association for the Study of Lung Cancer (IASLC) proposed a revision to the Union Internationale Contre le Cancer (UICC-6) staging system for non–small cell lung cancer. The goal of our study was to compare these systems in patients undergoing surgery for non–small cell lung cancer to determine whether one system is superior in staging operable disease.
Pathologic stages in 1154 patients undergoing complete resection over a 9-year period were analyzed. Patients were assigned a stage based on both IASLC and UICC-6 systems. We tested for statistically meaningful differences between the two staging systems using the Wilcoxon signed rank test and the permutation test.
The IASLC system is more effective than the UICC-6 system at ordering and differentiating patients (P = .009). Application of the IASLC system resulted in 202 (17.5%) patients being reassigned to a different stage (P = .012), with the most common shifts occurring from IB to IIA and IIIB to IIIA. The 5-year and median survivals of the IASLC IIIA patients including those shifted from the UICC-6 IIIB were 37% and 35 months, respectively. Reclassifying UICC-6 IIIB to IASLC IIIA did not reduce survival for the newly characterized IIIA cohort.
Our data confirm that the proposed IASLC staging system is more effective at differentiating stage than the UICC-6 system. Reclassifying patients from UICC-6 IIIB to IASLC IIIA will shift some patients from a stage previously considered unresectable to a stage frequently offered surgical resection. Further study and validation of the IASLC system are warranted.
PMCID: PMC2731793  PMID: 19619787
21.  Cardiac Autotransplantation for Malignant or Complex Primary Left-Heart Tumors 
Texas Heart Institute Journal  2008;35(3):296-300.
Malignant or complex benign tumors of the left heart can present a formidable challenge for complete resection, due to anatomic inaccessibility. Cardiac autotransplantation (cardiac explantation, ex-vivo tumor resection, reconstruction, and reimplantation) was introduced for complex benign primary left-heart cardiac tumors by Cooley and for malignant left-heart tumors by Reardon. Herein, we update our previously reported experience.
From April 1998 through July 2008, 20 patients underwent 21 cardiac autotransplantations for complex left-sided cardiac tumors that were nonresectable by traditional means. Demographics, tumor histology, operative data, and mortality rates were analyzed. Follow-up was complete in all patients.
Of the 20 patients, 17 had malignant lesions, and 3 had benign disease. Two patients had left ventricular lesions and the rest had left atrial lesions. Histology showed 7 malignant fibrous histiocytomas, 5 undifferentiated sarcomas, 3 leiomyosarcomas, 1 malignant osteosarcoma, 1 myxoid sarcoma, 2 paragangliomas, and 1 myxoma. Fourteen patients had previous resection of their cardiac tumors, and 1 patient had repeat autotransplantation for recurrent disease. There were no operative deaths in patients undergoing autotransplantation alone (0/15), and 3 operative deaths in patients undergoing combined cardiac autotransplantation and pneumonectomy (3/6, 50%). All 3 patients with benign disease survived surgery and are alive without recurrent disease. Local recurrence occurred in 3/18 patients with malignant disease: 1 underwent successful repeat autotransplantation and 2 are receiving chemotherapy. The mean survival for all patients with sarcoma is 22 months.
Cardiac autotransplantation enables complete resection and accurate reconstruction in many primary malignant and complex benign left-heart tumors.
PMCID: PMC2565530  PMID: 18941651
Heart neoplasms/mortality/surgery; heart transplantation/methods; replantation/methods; sarcoma/surgery; transplantation, autologous

Results 1-21 (21)