Laura N. Medford-Davis

Factors Associated With Local and Distant Recurrence and Survival in Patients With Resected Nonsmall Cell Lung Cancer

This study assessed the impact of surgical, histopathologic and patient‐related factors on the risks of local and distant recurrence and overall survival for patients with stages I through IIIA nonsmall cell lung carcinoma (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy.

Matched-pair and propensity score comparisons of outcomes of patients with clinical stage i non-small cell lung cancer treated with resection or stereotactic radiosurgery

Stereotactic body radiotherapy (SBRT) is an alternative to surgery for clinical stage I non–small cell lung cancer (NSCLC), but comparing its effectiveness is difficult because of differences in patient selection and staging.

Should Large Cell Neuroendocrine Lung Carcinoma be Classified and Treated as a Small Cell Lung Cancer or with Other Large Cell Carcinomas

Background: To compare the presenting and prognostic characteristics of patients with large cell neuroendocrine lung cancer (LCNELC) with those of patients with small cell lung cancer (SCLC) or other large cell carcinomas (OLCs) and to compare overall survival (OS) and lung cancer-specific survival (LCSS) rates for patients undergoing definitive resection without radiotherapy (S-NoRT). Methods: The Surveillance Epidemiology and End Results Database-17 from 2001 to 2007 was used. Differences between population characteristics were compared using &khgr;2 and Wilcoxon tests. The log-rank test and Cox models were used to compare differences in OS and LCSS. Results: There were 1211 patients with LCNELC (324 in the S-NoRT group), 8295 patients with OLC (1120 S-NoRT), and 35,304 patients with SCLC (355 S-NoRT). The proportion of all large cell carcinomas constituted by LCNELC increased from 8 to 21% during the study period; and the proportion of patients with large cell carcinoma undergoing S-NoRT increased from 16 to 26%. Presenting and histopathologic characteristics and treatment factors of patients undergoing S-NoRT for patients with LCNELC were more similar to those of patients with OLC than to those with SCLC. OS and LCSS rates for patients with LCNELC undergoing resection without radiation were similar to those of patients with OLC and better than those for patients with SCLC, but the differences were not statistically significant on multivariate analysis. Conclusions: The clinical, histopathologic, and biologic features of LCNELC are more similar to OLC than to SCLC. Therefore, LCNELC should continue to be classified and treated as a large cell carcinoma.

Confirmation of the role of diabetes in the local recurrence of surgically resected non-small cell lung cancer

PURPOSE We recently demonstrated that diabetes mellitus was an independent risk factor for local recurrence (LR) for patients undergoing resection of non-small cell lung cancer (NSCLC). This investigation was performed to confirm or refute this finding in a different patient cohort. MATERIALS AND METHODS Patients were eligible if they did not have a second primary cancer within 5 years of the original diagnosis, had at least 3-month follow-up, and did not receive radiotherapy. There were 373 and 168 patients in the original (P1) and confirmatory (P2) cohorts, respectively, with 66 and 30 patients with diabetes. RESULTS The median follow-up was 33 months (range, 3-98 months). Diabetes was an independent risk factor for LR in a Cox model in both the P2 (p=0.05, hazard ratio [HR] 2.15) and P1 (p=0.008, HR 1.90) cohorts, separately from BMI, glucose control, and the presence of the metabolic syndrome. The rates of LR in the patients with diabetes after combining the cohorts at 2, 3, and 5 years were 23%, 33%, and 56%, respectively; these rates were 15%, 19%, and 26% in non-diabetics. In multivariate Cox regression and competing risk analysis of the combined cohorts, the HRs for LR in patients with diabetes exceeded those of more established risk factors for LR including a 1-cm increase in tumor size and lymphovascular invasion. CONCLUSIONS Diabetes was confirmed to be an independent predictor of the risk of LR following resection of NSCLC.

Lobectomy leads to optimal survival in early-stage small cell lung cancer: A retrospective analysis

OBJECTIVE Stage I or II small cell lung cancer is rare. We evaluated the contemporary incidence of early-stage small cell lung cancer and defined its optimal local therapy. METHODS We analyzed the incidence, treatment patterns, and outcomes of 2214 patients with early-stage small cell lung cancer (1690 with stage I and 524 with stage II) identified from the Surveillance, Epidemiology, and End Results database from 1988 to 2005. RESULTS Early-stage small cell lung cancer constituted a stable proportion of all small cell lung cancers (3%-5%), lung cancers (0.10%-0.17%), and stage I lung cancers (1%-1.5%) until 2003 but, by 2005, increased significantly to 7%, 0.29%, and 2.2%, respectively (P < .0001). Surgery for early-stage small cell lung cancer peaked at 47% in 1990 but declined to 16% by 2005. Patients treated with lobectomy or greater resections (lobe) without radiotherapy had longer median survival (50 months) than those treated with sublobar resections (sublobe) without radiotherapy (30 months, P = .006) or those treated with radiotherapy alone (20 months, P < .0001). Patients undergoing sublobe without radiotherapy also demonstrated superior survival than patients receiving radiotherapy alone (P = .002). The use or omission of radiotherapy made no difference after limited resection (30 vs 28 months, P = .6). Multivariable analysis found survival independently related to age, year of diagnosis, tumor size, stage, and treatment (lobe vs sublobe vs radiotherapy alone). CONCLUSIONS Surgery is an underused modality in the management of early-stage small cell lung cancer. Lobectomy provides optimal local control and leads to superior survival. Although sublobar resection proved inferior to lobectomy, it conferred a survival advantage superior to radiotherapy alone. The addition of radiotherapy to resection provided no additional benefit.

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer

The objective of this study was to examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients who undergo potentially curative resection for stage I nonsmall cell lung cancer (NSCLC).

FAILURE RATES AND PATTERNS OF RECURRENCE IN PATIENTS WITH RESECTED N1 NON-SMALL-CELL LUNG CANCER

PURPOSE To examine the local and distant recurrence rates and patterns of failure in patients undergoing potentially curative resection of N1 non-small-cell lung cancer. METHODS AND MATERIALS The study included 60 consecutive unirradiated patients treated from 2000 to 2006. Median follow-up was 30 months. Failure rates were calculated by the Kaplan-Meier method. A univariate Cox proportional hazard model was used to assess factors associated with recurrence. RESULTS Local and distant failure rates (as the first site of failure) at 2, 3, and 5 years were 33%, 33%, and 46%; and 26%, 26%, and 32%, respectively. The most common site of local failure was in the mediastinum; 12 of 18 local recurrences would have been included within proposed postoperative radiotherapy fields. Patients who received chemotherapy were found to be at increased risk of local failure, whereas those who underwent pneumonectomy or who had more positive nodes had significantly increased risks of distant failure. CONCLUSIONS Patients with resected non-small-cell lung cancer who have N1 disease are at substantial risk of local recurrence as the first site of relapse, which is greater than the risk of distant failure. The role of postoperative radiotherapy in such patients should be revisited in the era of adjuvant chemotherapy.

Derangements of Potassium

Changes in potassium elimination, primarily due to the renal and GI systems, and shifting potassium between the intracellular and extracellular spaces cause potassium derangement. Symptoms are vague, but can be cardiac, musculoskeletal, or gastrointestinal. There are no absolute guidelines for when to treat, but it is generally recommended when the patient is symptomatic or has ECG changes. Treatment of hyperkalemia includes cardiac membrane stabilization with IV calcium, insulin and beta-antagonists to push potassium intracellularly, and dialysis. Neither sodium bicarbonate nor kayexelate are recommended. Treatment of symptomatic hypokalemia consists of PO or IV repletion with potassium chloride and magnesium sulfate.

Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

PURPOSE Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. METHODS AND MATERIALS A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. RESULTS The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. CONCLUSIONS Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

Identification of Stage I Non-small Cell Lung Cancer Patients at High Risk for Local Recurrence Following Sublobar Resection

OBJECTIVE An increasing proportion of patients with stage I non-small cell lung cancer (NSCLC) is undergoing sublobar resection (L-). However, there is little information about the risks and correlates of local recurrence (LR) after such surgery, especially compared with patients undergoing lobectomy (L+). METHODS Ninety-three and 318 consecutive patients with stage I NSCLC underwent L- and L+, respectively, from 2000 to 2006. Median follow-up was 34 months. RESULTS In the L- group, the LR rates at 2, 3, and 5 years were 13%, 24%, and 40%, respectively. The risk of LR was significantly associated with tumor grade, tumor size, and T stage. The crude risk of LR was 33.8% (21 of 62) for patients whose tumors were grade ≥ 2. In the L+ group, the LR rates at 2, 3, and 5 years were 14%, 19%, and 24%, respectively. The risk of LR significantly increased with increasing tumor size, length of hospital stay, and the presence of diabetes. The L- group experienced a significant increase in failure in the bronchial stump/staple line compared with the L+ group (10% vs 3%; P = .04) and nonsignificant trends toward increased ipsilateral hilar and subcarinal failure rates. CONCLUSIONS Patients with stage I NSCLC who undergo L- have an increased risk of LR compared with patients undergoing L+, particularly when they have tumors grade ≥ 2 or tumor size > 2 cm. If L- is considered, additional local therapy should be considered to reduce this risk of LR, especially with tumors grade ≥ 2 or size > 2 cm.