Phase II study of perioperative chemotherapy with cisplatin and pemetrexed in non-small-cell lung cancer.

INTRODUCTION: Pathologic complete response (pCR) with neoadjuvant chemotherapy is associated with improved survival in many solid tumors. We evaluated pCR rate of cisplatin with pemetrexed in non-small-cell lung cancer. METHODS: Patients with stages IB to IIIA non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1 were enrolled in this single-arm phase II trial using two-stage design with 90% power to detect pCR rate of more than or equal to 10%. Pretreatment mediastinal lymph node biopsy was required. Patients received three cycles of cisplatin 75 mg/m with pemetrexed 500 mg/m (day 1 every 21 days) preoperatively and additional two cycles within 60 to 80 days after surgery. The primary end point was pCR. Polymorphisms in FPGS, GGH, SLC19A1, and TYMS genes were correlated with treatment outcomes. RESULTS: Thirty-eight patients were enrolled, with median age of 62.5 years. Preoperatively, 26% had squamous histology, and 34% had biopsy-proven N2 involvement. R0 resection was achieved in 94% of the 34 patients who underwent surgery, and 54% had documented N2 clearance. There was no pCR seen. Median disease-free survival (DFS) and overall survival of these patients have not yet been reached in contrast to median of 13.8 and 24.2 months, respectively, in patients with persistent N2 disease (p = 0.3241 and p = 0.1022, respectively). There was a statistically significant association between DFS and postoperative tumor, node, metastasis stage (p = 0.0429), SLC19A1 rs3788189 TT genotype (p = 0.0821), and viable tumor defined as less than or equal to 10% of resected specimen (p = 0.026). CONCLUSION: The primary end point was not met. Patients with N2 clearance, less than or equal to 10% viable tumor in the resected specimen, and SLC19A1 rs3788189 TT genotype have favorable DFS outcomes.

Objective review of mediastinal lymph node examination in a lung cancer resection cohort.

BACKGROUND: Accurate staging of resected lung cancer requires mediastinal lymph node (MLN) examination. MLN dissection (MLND) and systematic sampling (SS) are acceptable procedures; random sampling (RS) and no sampling (NS) are not. Forty percent of US lung cancer resections have NS. We closely examined the pattern of MLN examination in a lung resection cohort. METHODS: This is a retrospective review of all lung cancer resections in Memphis, TN, from 2004 to 2007. We compared operating surgeons' claims to the pathology report and an audit of the operation narrative by an independent surgeon. RESULTS: Forty-five percent of resections were reported by surgeons as MLND, 8% RS, and 48% NS. None met pathology criteria for MLND, 9% were SS, 50% were RS, and 42% were NS. The concordance rate between the operating surgeon and pathology report was 39%. The surgeon audit suggested 29% of resections had MLND, 26% RS, and 45% NS. Concordance between operating and auditing surgeons was 71%. Sublobar resection, T1 stage, and age were associated with NS. CONCLUSIONS: Most resections had suboptimal MLN examination. Concordance was poor between surgeon claims, objective review of pathology reports, and an independent surgeon audit. The higher concordance between operating and auditing surgeons may suggest incomplete pathology examination of MLN material. The terms used by operating surgeons to describe MLN retrieval were often inaccurate.

Pathologic lymph node staging practice and stage-predicted survival after resection of lung cancer.

BACKGROUND: Lymph node status is the most important prognostic factor in resectable nonsmall-cell lung cancer (NSCLC). We examined the relationship between the pattern of lymph node examination (including the number and anatomic location of resected lymph nodes), pathologic nodal stage, and survival after NSCLC resection. METHODS: Retrospective review of all NSCLC resections in the Memphis Metropolitan Area from January 1, 2004, to December 31, 2007. RESULTS: In 656 resections, the number of lymph nodes examined differed significantly between patients grouped by pathologic nodal stage (p<0.0001) and extent of resection (p<0.001). Thirty-seven percent of "mediastinal node-negative" patients had no mediastinal lymph nodes examined. Patients with pN1 and no mediastinal lymph node examination had better [corrected] survival than patients with mediastinal lymph node examination (p < 0.02) . Approximately 10% of patients with pN0 and pN2 disease had no hilar/intrapulmonary lymph nodes examined. CONCLUSIONS: Suboptimal lymph node staging was prevalent in this cohort. Large proportions of pN1 and pN0 patients were probably understaged. In patients with pathologic positive pulmonary/hilar lymph nodes, mediastinal lymph node examination was associated with poorer survival [corrected]. Interventions are needed to improve lymph node staging of NSCLC.

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

BACKGROUND: 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. METHODS: Medical records of patients who underwent curative-intent resection for NSCLC in the Memphis, TN metropolitan area from January 1, 2004 to December 31, 2007 were retrospectively reviewed (N = 746 patients). GQR criteria were obtained from the National Comprehensive Cancer Network (NCCN), the RADIANT adjuvant study of erlotinib, and the American College of Surgeons Oncology Group (ACOSOG) Z0030 study. Factors associated with or without achievement of GQR were evaluated. Categorical variables were compared using chi-square or Fisher exact test, and survival curves by the log-rank test. RESULTS: Twenty-three and one-half percent of patients met GQR criteria as established by RADIANT, 8.2% by NCCN, and 0.9% by ACOSOG. The most common limiting factor in achieving GQR was inadequate lymph node sampling. The only patient factor associated with GQR was race (African-Americans were more likely than Caucasians to have GQR per RADIANT and NCCN criteria [P = .022 and P = .0489, respectively]). There was no significant survival difference between GQR and non-GQR patients. CONCLUSIONS: The vast majority of curative-intent resections did not achieve GQR standards. The greatest deficit is in surgical sampling of mediastinal (Level 2) lymph nodes, but evaluation of Level 1 lymph nodes is also suboptimal. Interventions are needed to improve current surgical practices and achieve minimum standards for accurate staging, prognostication, and eligibility for clinical trials.

Does race affect outcomes in triple negative breast cancer?

BACKGROUND: There is discordance among studies assessing the impact of race on outcome of patients with Triple Negative Breast Cancer (TNBC). We assessed survival outcomes for African American (AA) versus Caucasian (CA) women with TNBC treated at an urban cancer center in Memphis, TN with a predominant AA patient population. METHODS: Patients with Stage I-III TNBC were identified from our breast database. Event free survival (EFS) and Breast cancer specific survival (BCSS) were the primary outcome measures. Cox proportional hazards models were fitted for EFS and BCSS. RESULTS: Of the 124 patients, 71% were AA. No significant association between race and stage (P = 0.21) or menopausal status (P = 0.15) was observed. Median age at diagnosis was significantly lower for AA versus CA women (49.5 vs. 55 years, P = 0.024). 92% of the patients received standard neo/adjuvant chemotherapy, with no significant difference in duration and type of chemotherapy between the races. With a median follow up of 23 months, 28% of AA vs. 19% of CA women had an event (P = 0.37). 3 year EFS and BCSS trended favorably towards CA race (77% vs. 64%, log rank P = 0.20 and 92% vs. 76%, P = 0.13 respectively) with a similar trend noted on multiple variable modeling (EFS: HR 0.62, P = 0.29; BCSS: HR 0.36, P = 0.18). AA women >/=50 years at diagnosis had a significantly worse BCSS than the CA women in that age group (P = 0.012). CONCLUSION: Older AA women with TNBC have a significantly worse breast cancer specific survival than their CA counterparts. Overall, there is a trend towards lower survival for AA women compared to Caucasians despite uniformity of tumor phenotype and treatment. The high early event rate, irrespective of race, underscores the need for effective therapies for women with TNBC.

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.