Andrea Wolf

Lobectomy Versus Sublobar Resection for Small (2 cm or Less) Non-Small Cell Lung Cancers

BACKGROUND We evaluated a cohort of patients who underwent resection for small (2 cm or less) non-small cell lung cancer (NSCLC) to determine if there is an association between extent of resection (lobar versus sublobar resection) and local recurrence or survival. METHODS We reviewed 468 consecutive patients who underwent resection for small NSCLC at our institution between 2000 and 2005. We excluded patients who had neoadjuvant therapy, active noncutaneous malignancies, pure bronchioalveolar carcinoma, lymph node (n = 53) or distant metastases at diagnosis, or multicentric cancers. Clinicopathologic data, recurrence, and vital status as of June 15, 2010, were retrieved. Overall and recurrence-free survival from surgery rates were assessed. RESULTS Two hundred thirty-eight patients underwent resection for primary solitary small NSCLC. Lobectomy (n = 84) was associated with longer overall (p = 0.0027) and recurrence-free (p = 0.0496) survival. Patients who underwent sublobar resection were older (p < 0.0001) and had worse pulmonary function (p < 0.0014). While there was a trend toward increased rate of local recurrence for sublobar resection (16% versus 8%, p = 0.1117), there was no difference in distant recurrence. Moreover, when lymph nodes were sampled with sublobar resection, local recurrence rate and overall and recurrence-free survival distributions were similar to those for lobectomy. CONCLUSIONS Sublobar resection is reasonable in older patients with limited cardiopulmonary function. For healthy patients, however, lobectomy remains the standard therapy, with sublobar resection with lymph node sampling representing an alternative to consider. These findings support continued effort to conduct a randomized trial of lobar versus sublobar resection, such as CALGB 140503.

Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection

OBJECTIVE Local recurrence limits long-term survival in patients with malignant pleural mesothelioma. We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors. METHODS Using a preoperative risk assessment algorithm we had previously developed and validated, we retrospectively identified a cohort of patients treated with cytoreductive surgery from 2001 to 2009. The patients had epithelial histologic findings on biopsy and were characterized as having a low risk of early recurrence and death (ie, tumor volume ≤ 500 cm(3) and were either men with a hemoglobin level of ≥ 13 g/dL or were women). Those patients who had received hyperthermic intraoperative cisplatin chemotherapy were compared with a comparison group of those who had not. Fishers exact test was used to determine the balance of prognostic factors. The Kaplan-Meier method and log-rank tests were used to estimate and compare the interval to recurrence and overall survival. Cox proportional hazards regression was used for multivariate analysis. RESULTS The cohort criteria identified 103 patients: 72 who received hyperthermic intraoperative cisplatin chemotherapy and 31 who did not. The groups were balanced for prognostic factors, except for the use of neoadjuvant chemotherapy (more common in the comparison group). The hyperthermic intraoperative cisplatin chemotherapy group exhibited a significantly longer interval to recurrence (27.1 vs 12.8 months) and overall survival (35.3 vs 22.8 months) than the comparison group. The improved interval to recurrence and overall survival for the hyperthermic intraoperative cisplatin chemotherapy group were particularly evident among the subgroups of patients who had not received hemithoracic radiotherapy and who had pathologic stage N1 or N2 lymph node metastases. CONCLUSIONS A favorable outcome and minimal incremental morbidity support the incorporation of hyperthermic intraoperative cisplatin chemotherapy into multimodality treatment strategies for patients with low-risk epithelial malignant pleural mesothelioma.

CT Screening for Lung Cancer: Nonsolid Nodules in Baseline and Annual Repeat Rounds

PURPOSE To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International Early Lung Cancer Action Program. MATERIALS AND METHODS A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages. RESULTS A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 [66%] of 485 vs 628 [26%] of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range [IQR], 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months). CONCLUSION Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.

Surgery for malignant pleural mesothelioma

The role of surgery for malignant pleural mesothelioma encompasses the need for rapid diagnosis, preoperative staging and surgical resection, and also the need for a greater biological understanding of this rare and aggressive malignancy. In the multimodality treatment paradigm, the goal of surgery is to provide a macroscopic complete resection (i.e., complete removal of all grossly visible tumor). Two operations have evolved: extrapleural pneumonectomy and pleurectomy/decortication. The former is indicated for patients with advanced locally invasive disease; the latter for patients with more superficial spread of tumor that spares the lung and fissures. If critical mediastinal structures (e.g., aorta and vertebral bodies) are found to be involved at thoracotomy, the tumor is classified as T4, and pleurectomy/decortication is recommended. Despite having more advanced disease, a subset of patients with favorable prognostic factors can experience extended survival by undergoing trimodality therapy with extrapleural pneumonectomy, chemotherapy and/or radiation. The influence of surgery goes beyond diagnosis and resection. Much of what we know about the biology of mesothelioma has been gleaned from studying the surgical pathophysiology, including the delineation of histopathologic subtypes, disease stage stratification with survival, the propensity for local (in contrast to systemic) recurrence, as well as the prognostic effect of epithelial versus nonepithelial cell type, extrapleural nodal involvement, tumor bulk and surgical margins. Pending the discovery of new drugs, the focus of clinical research over the next 5 years will emphasize refinements in patient selection, pathologic staging, molecular staging and other novel adjuvant therapies.

Epithelial Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy: Stratification of Survival With CT-Derived Tumor Volume

OBJECTIVE The purpose of this study was to assess the usefulness of CT-derived tumor volume, with control for other prognostic factors, for stratifying survival after surgery-based multimodality treatment of a large cohort of patients with epithelial malignant pleural mesothelioma. MATERIALS AND METHODS We retrospectively reviewed 338 patients with mesothelioma who underwent extrapleural pneumonectomy between 2001 and 2007. The study cohort comprised 88 patients with epithelial subtype tumors, DICOM-format CT scans, and data regarding neoadjuvant and adjuvant therapy. Tumor volume was calculated, and Kaplan-Meier survival and Cox regression analyses were performed to compare the estimated survival functions of patient subgroups based on volume and other covariates related to outcome (sex, age, preoperative platelet count, hemoglobin concentration, WBC count, clinical and pathologic TNM category, and administration of neoadjuvant and adjuvant therapy). A multivariate regression model was derived on the basis of the most significant univariate predictors. RESULTS The median estimated tumor volume was 319 cm(3) (range, 4-3256 cm(3)). In univariate analysis, tumor volume, hemoglobin concentration, platelet count, pathologic TNM category, and administration of adjuvant chemotherapy or radiation therapy met the criteria for inclusion in the reverse stepwise regression analysis. In the final model, tumor volume, hemoglobin concentration, and administration of adjuvant chemotherapy or radiotherapy were identified as independently associated with overall survival. CONCLUSION With control of prognostic covariates, CT-derived tumor volume can be used to stratify survival of patients with epithelial mesothelioma after extrapleural pneumonectomy and should be included in prognostic evaluation of patients for whom resection is being considered.

Clinical and pathological features of three-year survivors of malignant pleural mesothelioma following extrapleural pneumonectomy.

OBJECTIVE Surgery-based multimodality therapy is associated with long-term survival in a significant number of pleural mesothelioma patients. We explored factors associated with 3-year survival in patients with malignant pleural mesothelioma, who underwent extrapleural pneumonectomy, to help refine patient selection criteria for surgery and other therapies. METHODS With Institutional Review Board approval, we reviewed records in the International Mesothelioma Program Patient Data Registry to identify all patients, who underwent extrapleural pneumonectomy for malignant pleural mesothelioma between 1 January 1988 and 31 May 2007. Vital status as of 31 May 2010 was confirmed. Fishers exact test was used to compare dichotomous variables for patients who survived at least 3 years with those who did not. Kaplan-Meier analysis was used to estimate the cumulative survival probability for all 3-year survivors. RESULTS Among 636 patients who underwent extrapleural pneumonectomy, 117 (18%) survived at least 3 years following surgery, including 26 remaining alive and four lost to follow-up. Of the 3-year survivors, 39 (33%) were female, 61 (52%) had left-sided disease, and the median age was 56 years (range 27-77). Relatively more 3-year survivors were younger than, or at the median age (p=0.0005), or female (p=0.0007), had epithelial tumor histology (p<0.0001) and/or had normal white blood cell count (p=0.0001), hemoglobin (p<0.0001), or platelet count (p<0.0001) preoperatively. The median survival of the 117 patients who survived 3-years was 59 months. Among these patients, a significant association between age and survival was found only for women. CONCLUSIONS A significant proportion of patients undergoing extrapleural pneumonectomy for pleural mesothelioma experienced extended survival. Although favorable prognostic features were more common, the cohort of 3-year survivors included a substantial number of patients with late-stage disease. The longest survival (median greater than 7 years) was experienced by women under the median age of 56 years. These data support the role of macroscopic cytoreduction through extrapleural pneumonectomy in the context of multimodality therapy to extend survival for malignant pleural mesothelioma. Further efforts to treat micrometastatic disease and improve patient selection are warranted.

Surgical Techniques for Multimodality Treatment of Malignant Pleural Mesothelioma: Extrapleural Pneumonectomy and Pleurectomy/Decortication

Trimodality treatment of malignant pleural mesothelioma with cytoreductive surgery followed by radiation and chemotherapy has resulted in long-term survival for a select group of patients. Knowledge of the similarities and differences between the two operations that have evolved-extrapleural pneumonectomy and pleurectomy/decortication-is prerequisite to understanding the complex issues associated with patient selection, diagnosis, pathologic staging, preoperative assessment, perioperative management, and adjuvant treatment. Both operations are technically complex and should only be performed at experienced high-volume centers.

Characteristics of Malignant Pleural Mesothelioma in Women

BACKGROUND The incidence of malignant pleural mesothelioma (MPM) is higher in men than in women, likely due to increased occupational asbestos exposure among men. Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM. METHODS We reviewed 715 cases of MPM treated with extrapleural pneumonectomy at our institution between July 1987 and December 2008. Data for patients with epithelial and nonepithelial tumors were analyzed separately. Kaplan-Meier and Cox regression analyses were used to estimate survival for various cohorts to assess the relationship between gender and survival independent of age at surgery, stage, side, and preoperative laboratory studies. RESULTS Of the 702 patients with complete data available, 114 out of 450 patients with epithelial tumors and 31 out of 252 patients with nonepithelial histology were women. Women with epithelial (and not nonepithelial) disease were found to differ significantly from men with respect to younger age, higher rate of thrombocytosis, and longer survival after surgery. The effect of gender on survival of patients with epithelial disease persisted when controlling for age, stage, thrombocytosis, leukocytosis, and anemia with a multivariable analysis. No significant differences in survival were seen among patients with nonepithelial disease with regard to gender, age, or anemia. CONCLUSIONS In the absence of other negative prognostic factors, women with epithelial MPM demonstrated a survival advantage. These findings support an aggressive approach to treating MPM including extrapleural pneumonectomy in individuals with favorable prognostic predictors, particularly women with epithelial histology and no other risk factors.

Current Treatment of Mesothelioma: Extrapleural Pneumonectomy Versus Pleurectomy/Decortication

The role of surgical resection in malignant pleural mesothelioma (MPM) is based on the principle of macroscopic resection of a solid tumor with adjuvant therapy to treat micrometastatic disease. Extrapleural pneumonectomy (EPP) and pleurectomy decortication (P/D) have been developed in this context. Cancer-directed surgery for MPM is associated with a 5-year survival rate of 15%. Evidence indicates that P/D is better tolerated by patients and suggests survival is no worse when compared with EPP. Although EPP is still performed in highly selected cases, the authors advocate radical P/D whenever possible for patients with MPM.

CT Screening for Lung Cancer: Part-Solid Nodules in Baseline and Annual Repeat Rounds

OBJECTIVE The purpose of this study was to assess the frequencies of identifying participants with part-solid nodules, of diagnostic pursuit, of diagnoses of lung cancer, and long-term lung cancer survival in baseline and annual repeat rounds of CT screening in the International Early Lung Cancer Action Project. MATERIALS AND METHODS Screenings were performed under a common protocol. Participants with solid, nonsolid, and part-solid nodules and the diagnoses of lung cancer were documented. RESULTS Part-solid nodules were identified in 2892 of 57,496 (5.0%) baseline screening studies; 567 (19.6%) of these nodules resolved or decreased in size. Diagnostic pursuit led to the diagnosis of adenocarcinoma in 79 cases, all clinical stage I. At resection, one nodule (12-mm solid component) had a single N2 metastasis. A new part-solid nodule was identified in 541 of 64,677 (0.8%) annual repeat screenings; 377 (69.7%) of these nodules resolved or decreased in size. In eight cases among the 541, the diagnosis of adenocarcinoma manifesting as a part solid nodule was made; on retrospective review the nodule originally had been a nonsolid nodule. In another 20 cases, the cancer originally had manifested as a nonsolid nodule but had progressed to become part-solid at annual repeat screening before any diagnosis was pursued. These 28 annual repeat cases of lung cancer were all pathologic stage IA. Of the 107 cases of lung cancer (79 baseline cases and 28 annual repeat cases), 106 were surgically resected, and one baseline case was followed up with imaging for 4 years. The lung cancer survival rate was 100% with a median follow-up period from diagnosis of 89 months (interquartile range, 52-134 months). CONCLUSION Lung cancers manifesting as part-solid nodules at repeat screening studies all started as nonsolid nodules. Among 107 cases of adenocarcinoma manifesting as a part-solid nodule, a single lymph node metastasis was found in a single case (solid component, 12 mm).