Raymond U. Osarogiagbon

Mediastinal Lymph Node Examination and Survival in Resected Early-Stage Non–Small-Cell Lung Cancer in the Surveillance, Epidemiology, and End Results Database

Background: Pathologic nodal stage is the key prognostic factor in resectable non–small-cell lung cancer (NSCLC). Mediastinal lymph node (MLN) metastasis connotes a poor prognosis. Yet, some NSCLC resections exclude MLN examination. Methods: We analyzed U.S. Surveillance, Epidemiology, and End Results program data from 1998 to 2002 to quantify the long-term survival impact of failure to examine MLN in resected NSCLC. We used Kaplan–Meier methods to compare the unadjusted survival difference between patients with, and without, MLN examination, and Cox proportional hazards and competing risk models to serially adjust for the impact of risk factors on survival differences. Results: Sixty-two percent of patients with pathologic N0 or N1 NSCLC had no MLN examined. Overall 5-year survival rates were 52% for those with, versus 47% for those without, MLN examination; lung cancer-specific survival rates were 63% versus 58% respectively (p < 0.001); nonlung cancer mortality was identical between cohorts. Adjusting for potential confounders, MLN examination was associated with a 7% reduction in all-cause mortality (hazard ratio, 0.93; confidence interval, 0.88–0.97; p = 0.002), and 11% reduction in lung cancer-specific mortality (hazard ratio, 0.89; 95% confidence interval, 0.84–0.95; p < 0.001) rates. The excess risk in 1 year’s cohort of U.S. lung resections was 3150 lives over 5 years. Conclusions: Failure to examine MLN was a common practice in MLN-negative NSCLC resections, which significantly impaired long-term survival. Efforts to understand the etiology of this quality gap, and measures to eliminate it, are warranted.

Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

PURPOSE Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. PATIENTS AND METHODS We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. RESULTS We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. CONCLUSION Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

Number of Lymph Nodes Associated With Maximal Reduction of Long-Term Mortality Risk in Pathologic Node-Negative Non–Small Cell Lung Cancer

BACKGROUND Forty-four percent of patients with pathologic node negative (pN0) non-small cell lung cancer (NSCLC) die within 5 years of curative-intent surgical procedures. Heterogeneity in pathologic nodal examination practice raises concerns about the accuracy of nodal staging in these patients. We hypothesized a reciprocal relationship between the number of lymph nodes examined and the probability of missed lymph node metastasis and sought to identify the number of lymph nodes associated with the lowest mortality risk in pN0 NSCLC. METHODS We analyzed resections for first primary pN0 NSCLC in the United States Surveillance, Epidemiology, and End Results (SEER) database from 1998 to 2009, with survival updated to December 31, 2009. RESULTS In 24,650 eligible patients, there was a significant sequential reduction in mortality risk with examination of more lymph nodes. The lowest mortality risk occurred in those with 18 to 21 lymph nodes examined. The hazard ratio for all-cause mortality was 0.65 and the 95% confidence interval (CI) was 0.57 to 0.73; for lung cancer-specific mortality, hazard ratio was 0.62 and CI was 0.53 to 0.73 (p<0.001 for both). The median number of lymph nodes examined was only 6. CONCLUSIONS Lymph node evaluation falls far short of optimal in patients with resected pN0 NSCLC, raising the odds of underestimation of long-term mortality risk and failure to identify candidates for postoperative adjuvant therapy. This represents a major quality gap for which corrective intervention is warranted.

A Transition Pilot Program for Adolescents With Sickle Cell Disease

INTRODUCTION Transition from pediatric to adult care is challenging for adolescents with chronic illnesses, including those with sickle cell disease (SCD). We describe a pilot program created to facilitate transition from pediatric to adult care by helping adolescents with SCD identify an adult medical home. METHODS We investigated the feasibility of this program by evaluation of overall participation, satisfaction, and acceptance. A secondary objective was to compare the proportion of adolescents who fulfilled a first appointment with an adult hematologist among participants and nonparticipants. RESULTS During the first 18 months of the program, 83 adolescents were invited and 34 (41%) agreed to participate; 25 (74%) completed their first visit within 3 months after leaving the pediatric program, compared with 16 of 49 (33%) of nonparticipants (p = .0002). Overall, 41 of 83 adolescents (49%) completed an appointment with an adult SCD program, regardless of program participation, in contrast with 11 of 75 adolescents (15%) who did so during the 18 months before the program was created (p < .0001). DISCUSSION This transition pilot program was feasible, and most adolescent participants with SCD established an adult medical home.

Quality of surgical resection for nonsmall cell lung cancer in a US metropolitan area

Curative treatment of early stage nonsmall cell lung cancer (NSCLC) requires good quality surgical resection (GQR). The degree of compliance with national recommendations for GQR is poorly defined. We sought to quantitatively define the degree of compliance in a consecutive series of NSCLC resections.

Colorectal Cancers from Distinct Ancestral Populations Show Variations in BRAF Mutation Frequency

It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer.

Outcome of Surgical Resection for Pathologic N0 and Nx Non-small Cell Lung Cancer

Purpose: Metastasis to lymph nodes (LNs) connotes poor prognosis in non-small cell lung cancer (NSCLC). Sufficient LNs must be examined to accurately determine LN negativity. Patients with no LNs examined (pNx) have an indeterminate stage, may have undetected disease and erroneous assignment to a low-risk group. To evaluate this possibility, we compared the survival of patients with node-negative disease and at least one LN examined (pN0) to those with pNx. Methods: Retrospective analysis of all resections for NSCLC from January 1, 2004 to December 31, 2007 at hospitals in the Memphis Metropolitan Area. Results: Of 746 resections, 90 (12.1%) were Nx; 506 (67.8%) N0. Demographic and histologic characteristics were similar. A total of 54.4% Nx patients had sublobar resection, compared with 5.5% N0 (p < 0.0001). In the N0 cohort, the median (range) number of LNs was 5 (1-45); N1 LNs, 3 (0-38); N2 LNs, 1 (0-29); 35.4% had no mediastinal LNs examined; 9.1% had only mediastinal LNs. Eighty- five percent of N0 patients had less than 10 LNs. The 3-year survival estimate for the T1NxM0 versus T1N0M0 patients was 70% versus 79% (p = 0.17); for T2NxM0 versus T2N0M0, it was 25% versus 65% (p < 0.01). Conclusions: A high percentage of patients undergoing surgical resection for NSCLC have no LNs examined, most of these patients have had sublobar resection. Majority with node-negative disease have fewer than 10 LNs, a large proportion have no mediastinal LNs, raising the possibility of understaging. Patients with pT2Nx do significantly worse than those with pT2N0.

Use of a Surgical Specimen-Collection Kit to Improve Mediastinal Lymph-Node Examination of Resectable Lung Cancer

Introduction: Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non–small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non–small-cell lung cancer by using a prelabeled specimen-collection kit. Methods: Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. Results: The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. Conclusions: The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.

'One-stop shop': lung cancer patients' and caregivers' perceptions of multidisciplinary care in a community healthcare setting.

BACKGROUND Multidisciplinary care is rarely practiced in community healthcare settings where the majority of patients receive lung cancer care in the US. We sought direct input from patients and their informal caregivers on their experience of lung cancer care delivery. METHODS We conducted focus groups of patient and caregiver dyads. Patients had received care for lung cancer in or out of a multidisciplinary thoracic oncology clinic coordinated by a nurse navigator. Focus groups were audiotaped, transcribed, and analyzed using Creswells 7-step process. Recurring overlapping themes were developed using constant comparative methods within the Grounded Theory framework. RESULTS A total of 46 participants were interviewed in focus groups of 5 patient-caregiver dyads. Overlapping themes were a perception that multidisciplinary care improved physician collaboration, patient-physician communication, and patient convenience, while reducing redundancy in testing. Improved coordination decreased confusion, stress, and anxiety. Negative experience of serial care included poor communication among physicians, insensitive communication about illness, delays in diagnosis and treatment, misdiagnosis, and mistreatment. Physician-to-physician communication and patient education were suggested areas for improvement in the multidisciplinary model. CONCLUSIONS Multidisciplinary care was perceived as more patient-centered, effective, safe, and efficient than standard serial care. It was also believed to improve the timeliness of care and equitable access to high quality care. Additional studies to compare these perspectives to those of other key stakeholders, including clinicians, hospital administrators and representatives of third party payers, will facilitate better understanding of the role of multidisciplinary care programs in lung cancer care delivery.

Erlotinib therapy after initial platinum doublet therapy in patients with EGFR wild type non-small cell lung cancer: results of a combined patient-level analysis of the NCIC CTG BR.21 and SATURN trials

BACKGROUND The clinical benefit of erlotinib in treating epidermal growth factor receptor (EGFR) wildtype non-small cell lung cancer (NSCLC) has been questioned. We examined the impact of erlotinib in confirmed EGFR wildtype patients in two placebo-controlled phase III trials: the National Cancer Institute of Canada Clinical Trials Group BR.21 (BR.21) and Sequential Tarceva in Unresectable Non-Small Cell Lung Cancer (SATURN) trials. METHODS Combined re-analysis of progression-free survival (PFS) and overall survival (OS) in patients with known wildtype EGFR, estimated by Kaplan-Meier curves and compared by two-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Additional analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations. RESULTS Mutation status was known in 25% (n=184 of 731) of the BR.21, and 49% (n=437 of 889) of the SATURN populations, of which 82% (n=150) and 89% (n=388) respectively had wildtype EGFR. HR for PFS was 0.71 (95% CI, 0.59-0.85; P<0.01) and for OS was 0.72 (95% CI, 0.59-0.88; P<0.01). Baseline characteristics and outcome (PFS and OS) distributions were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR wildtype data. Erlotinib benefit was sustained in all clinical subsets. CONCLUSIONS Erlotinib provided a consistent and significant improvement in survival for patients with EGFR wildtype NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating mutations of EGFR.