Histopathologic Cell Type Research Articles

Extended resections in the treatment of locally advanced lung cancer

Background: This study aims to evaluate surgical outcomes and prognosis in patients who underwent extended lung resection for locally advanced lung cancer. Methods: Between January 2015 and December 2019, a total of 61 patients (60 males, 1 female; mean age: 61.7±12.2 years; range, 32 to 90 years) with locally advanced non-small-cell lung cancer who underwent extended lung resection were retrospectively analyzed. Data including age, sex, comorbid diseases, symptoms, smoking status, pulmonary function test results, tumor location, methods used for preoperative tissue diagnosis, histopathological cell type, type of surgical resection, pathological stage, nodal involvement, postoperative complications, types of adjuvant therapy, and mortality rate were recorded. Survival and the factors affecting survival were examined. Results: Seven (11.4%) patients had Stage IIIB, 40 (65.5%) patients had Stage IIIA, and 14 (22.9%) patients had Stage IB disease. Intrapericardial pneumonectomy accounted for 30 (49.1%) of all extended lung resections. Chemotherapy was administered to 31 (50.8%) patients and chemoradiotherapy to 24 (39.3%) patients in the postoperative period. In the survival analysis, 70-month survival rate was calculated as 63.9% and the median survival was 48 months. There was a statistically significant association between survival with adjuvant chemotherapy and chemoradiotherapy (p=0.003). The mortality rate at 70 months of follow-up was 36.1%. Conclusion: Extended lung resection contributes significantly to the improvement of survival rates in carefully selected locally advanced cases. Particularly with adjuvant chemotherapy, local recurrences can be prevented, and survival rates can be improved.

Genetic Basis and Molecular Mechanisms of Uveal Melanoma Metastasis: A Focus on Prognosis.

Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.

Early-Stage Non-Small Cell Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Institution.

IntroductionThe gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution.Materials and methodsThis retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox’s proportional hazard regression analysis.ResultsThe median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk.The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE). ConclusionOur experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.

Clinicopathological Profile of Patients with Lung Carcinoma in a Tertiary Care Center

Abstract Introduction Among malignant diseases, lung carcinoma is the most common cancer in men worldwide in terms of both incidence and mortality. Its increasing incidence in developing countries like India is an important public health problem. This work aimed to study the demographic, clinical, radiological, and histological features of patients with confirmed lung cancer. Materials and Methods A total of 50 patients with histologically confirmed lung cancer at a tertiary care center in India from August 2016 to September 2018 were studied and analyzed. Results Out of 50 diagnosed lung cancer patients, 86% were men and 14% women; 31 (62%) patients were aged more than 60 years. Majority were smokers (84%) and all were men. Cough (94%) was the most common presenting symptom followed by dyspnea (68%), chest pain (48%), and hemoptysis (38%). Of the 50 patients, 29 (58%) had soft tissue density mass lesion on radiograph. Squamous cell carcinoma (SCC) was the diagnosed histological cell type in 24 (48%) patients and adenocarcinoma in 21 (42%) patients. Distant metastasis was observed in 20 (40%) patients. Conclusion In this study, the most common histopathological cell type is SCC. Patients aged more than 50 years and smokers are at high risk of lung cancer. Patients with a smoking history and persistent respiratory symptoms should be promptly evaluated for lung malignancy.

Non–small cell lung cancer in never- and ever-smokers: Is it the same disease?

ObjectivesTo investigate differences in presentation, pathology, and outcomes after resection of non–small cell lung cancer (NSCLC) in never-smokers versus ever-smokers. MethodsFrom January 2006 to July 2016, 172 never-smokers and 1376 ever-smokers with NSCLC underwent pulmonary resection. The 2 cohorts were matched on patient characteristics, histopathological cancer cell type, and pathological stage group using a weighted balancing score, and overall survival and cancer recurrence were compared by pathological stage. Random forests for survival was used to identify granular cancer characteristics with different survival and cancer recurrence importance between groups. ResultsIn never-smokers, the prevalence of NSCLC was more frequent in women than in men (63% [n = 109] vs 45% [n = 63]). Compared with ever-smokers, never-smokers had less upper-lobe disease (53% [n = 91] vs 62% [n = 855]) and more adenocarcinoma (88% [n = 151] vs 62% [n = 845]). Postoperative complications were similar. Never-smokers had a lower prevalence of non–lung cancer deaths than ever-smokers (13% vs 23% at 5 years; P = .006). Among matched pairs, never-smokers had better overall survival at 5 years in pathological stage I (96% vs 78%), but worse survival in stage II (54% vs 78%). Tumor size, N category, and histopathological cell type were more important drivers of mortality and cancer recurrence in never-smokers than in ever-smokers. ConclusionsNSCLC in never-smokers affects women more than men and presents with different anatomic and histopathological distributions. Matched never-smokers have better or equivalent outcomes than ever-smokers in pathological stage I cancer, but are less likely to survive and to be cured of cancer as tumor burden increases. These findings suggest that there might be unique tumor or host behaviors differentially impacting survival of never- and ever-smoking patients with NSCLC.

Prognostic significance of tumor size for primary invasive cutaneous melanoma: A population-based study, 2004-2016.

BackgroundThis study aimed to assess the independent prognostic value of tumor size compared with other clinical and pathologic features of primary invasive cutaneous melanoma (CM).MethodsThis study included 28,593 patients with primary invasive CM in Surveillance, Epidemiology, and End Results Program database diagnosed from 2004 through 2016. Tumor size was divided into five subgroups (≤6, 7‐12, 13‐30, 31‐42, and >42 mm). The primary endpoint was melanoma‐specific survival (MSS).ResultsThe relationship between tumor size and survival was piecewise. After adjusting for age, sex, primary site, histopathologic cell type, Breslow thickness, ulceration, mitotic rate, regional metastasis, and distant metastasis, the hazard ratio (HR) of MSS increased with increasing tumor size until a peak at 31‐42 mm (HRs, 1.33, 1.59, 2.41, respectively; all P < .0001), and then decreased when tumor size was larger than 42 mm using tumor size ≤ 6 mm as the reference (HR, 2.11; 95% confidence interval [CI], 1.84 −2.42; P < .0001). This pattern mostly remained after stratification by T subcategories from T1 to T4 in localized primary CM except that tumor size >42 mm subgroup had the shortest MSS in T4. In addition, tumor size with a cutoff value of 12 mm showed stronger prognostic value for MSS (HR, 2.32; 95% CI, 1.80‐2.98; P < .0001) than Breslow thickness and mitotic rate in primary CM with T1N0M0.ConclusionsTumor size was an important independent prognostic factor for MSS in patients with primary invasive CM. Tumor size larger than 30 mm would provide additional and important prognostic information in each T subcategory of localized CM. Furthermore, tumor size with a cutoff value of 12 mm has great potential in improving the accuracy of melanoma T1 substaging.

Imaging and Staging of Esophageal Malignancy

Squamous cell carcinoma (SCC) and adenocarcinoma are the two main cell types of esophageal cancer. Esophageal adenocarcinoma is rapidly increasing in incidence in Western countries, particular in elderly white males. Histopathologic cell type affects the survival of clinically and pathologically staged patients, but less so pathologically staged patients following neoadjuvant therapy. The survival of early- and intermediate-stage patients with SCC is worse than for those with similarly staged adenocarcinoma. Unfortunately, patients often present with either cell type of esophageal carcinoma at an advanced stage. Various imaging modalities are necessary to adequately stage patients with esophageal cancer due to the length of the esophagus and patterns of spread that frequently involve the neck, thorax, and abdomen. Despite advances in imaging, the accuracy of clinical staging is limited, which results in different survival profiles for clinical stage groups compared with pathologic stage groups. Since clinical staging based on imaging remains unpredictable and inaccurate, the eighth edition of the AJCC Cancer Staging Manual has now expanded staging to allow for three different opportunities. Separate classifications now include clinical (cTNM), pathologic (pTNM), and postneoadjuvant pathologic (ypTNM) staging. It is hoped that the use of these three stage groups will improve our ability to provide precise care to patients with esophageal cancer. This review contains 2 figures, 9 tables, and 23 references. Key words: Esophageal cancer, Esophagography, Endoscopic ultrasonography, Invasive esophageal cancer, Staging of esophageal cancer, Gastroesophageal junction carcinoma

Cancer of the esophagus and esophagogastric junction-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.

8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice.

The 8th edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects survival of clinically and pathologically staged patients, requiring separate groupings for each cell type, but ypTNM groupings are identical for both cell types. Clinical categories, typically obtained by imaging with minimal histologic information, are limited by resolution of each method. Strengths and shortcomings of clinical staging methods should be recognized. Complementary cytology or histopathology findings may augment imaging and aid initial treatment decision-making. However, prognostication using clinical stage groups remains coarse and inaccurate compared with pTNM. Pathologic staging is losing its relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains relevant for early-stage cancers and as a staging and survival reference point. Although pathologic stage could facilitate decision-making, its use to direct postoperative adjuvant therapy awaits more effective treatment. Prognostication using pathologic stage groups is the most refined of all classifications. Postneoadjuvant staging (ypTNM) is introduced by the AJCC but not adopted by the Union for International Cancer Control (UICC). Drivers of this addition include absence of equivalent pathologic (pTNM) categories for categories peculiar to the postneoadjuvant state (ypT0N0-3M0 and ypTisN0-3M0), dissimilar stage group compositions, and markedly different survival profiles. Thus, prognostication is specific for patients undergoing neoadjuvant therapy. The role of ypTNM classification in additional treatment decision-making is currently limited. Precision cancer care advances are necessary for this information to be clinically useful.

ED05.04 What’s New in Esophageal Cancer Staging?

ED05.04 What’s New in Esophageal Cancer Staging?

Cancer of the Esophagus and Esophagogastric Junction: An Eighth Edition Staging Primer.

This primer for eighth edition staging of esophageal and esophagogastric epithelial cancers presents separate classifications for the clinical (cTNM), pathologic (pTNM), and postneoadjuvant pathologic (ypTNM) stage groups, which are no longer shared. For pTNM, pT1 has been subcategorized as pT1a and pT1b for the subgrouping pStage I adenocarcinoma and squamous cell carcinoma. A new, simplified esophagus-specific regional lymph node map has been introduced. Undifferentiated histologic grade (G4) has been eliminated; additional analysis is required to expose histopathologic cell type. Location has been removed as a category for pT2N0M0 squamous cell cancer. The definition of the esophagogastric junction has been revised. ypTNM stage groups are identical for both histopathologic cell types, unlike those for cTNM and pTNM.

New TNM staging system for esophageal cancer: what chest radiologists need to know.

Esophageal cancer is a leading cause of cancer-related deaths worldwide, and the 5-year relative survival rate remains less than 20% in the United States. The treatment of esophageal cancer should be stage specific for better clinical outcomes. Recent treatment paradigms tend to involve a multimodality approach to management, which includes surgical resection and preoperative or definitive chemoradiation therapy. Accurate pretreatment staging of esophageal cancer is integral for assessing operability and determining a suitable treatment plan. The American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) have published the seventh edition of the staging manual for cancer in the esophagus and esophagogastric junction. Unlike the sixth edition, the revised staging manual is data driven and harmonized with the staging of stomach cancer. Improvements include new definitions for the anatomic classifications Tis, T4, regional lymph node, N, and M and the addition of nonanatomic cancer characteristics (histopathologic cell type, histologic grade, and cancer location). Given the recent increase in the incidence of adenocarcinoma of the distal esophagus, esophagogastric junction, and gastric cardia, the staging of tumors in the esophagogastric junction has been addressed. Radiologists must understand the details of the seventh edition of the AJCC-UICC staging system for esophageal cancer and use appropriate imaging modalities, such as computed tomography (CT), endoscopic ultrasonography, and positron emission tomography/CT, for initial staging.

Metabolic activity of primary uveal melanoma on PET/CT scan and its relationship with monosomy 3 and other prognostic factors

PurposeTo correlate the metabolic activity of primary uveal melanoma on positron emission tomography (PET)/CT scan with known clinical and pathological prognostic factors.MethodsA retrospective cohort analysis of eyes enucleated for uveal...

Esophageal submucosa: The watershed for esophageal cancer

Submucosal esophageal cancers (pT1b) are considered superficial, implying good survival. However, some are advanced, metastasizing to regional lymph nodes. Interplay of cancer characteristics and lymphatic anatomy may create a watershed, demarcating low-risk from high-risk cancers. Therefore, we characterized submucosal cancers according to depth of invasion and identified those with high likelihood of lymph node metastases and poor survival. From 1983 to 2010, 120 patients underwent esophagectomy for submucosal cancers at Cleveland Clinic. Correlations were sought among cancer characteristics (location, dimensions, histopathologic cell type, histologic grade, and lymphovascular invasion [LVI]), and their associations with lymph node metastasis were identified by logistic regression. Associations with mortality were identified by Cox regression. As submucosal invasion increased, cancer length (P < .001), width (P<.001), area (P<.001), LVI (P=.007), and grade (P=.05) increased. Invasion of the deep submucosa (P < .001) and LVI (P=.06) predicted lymph node metastases: 45% (23/51) of deep versus 10% (3/29) of middle-third and 7.5% (3/40) of inner-third cancers had lymph node metastases, as did 46% (12/26) with LVI versus 18% (17/94) without. Older age and lymph node metastases predicted worse 5-year survival: 94% for younger pN0 patients, 62% for older pN0 patients, and 36% for pN1-2 patients regardless of age. Submucosal cancer characteristics and lymphatic anatomy create a watershed for regional lymph node metastases in the deep submucosa. This previously unrecognized divide distinguishes superficial submucosal cancers with good survival from deep submucosal cancers with poor survival. Aggressive therapy of more superficial cancers is critical before submucosal invasion occurs.

Node-Negative Non-small Cell Lung Cancer: Pathological Staging and Survival in 1765 Consecutive Cases

This study aimed to evaluate prognostic factors in patients with node-negative non-small cell lung cancer and to assess revised International Association for the Study of Lung Cancer staging recommendations for this group. A retrospective analysis of 1765 consecutive pathologically node-negative patients treated by surgical resection between 1984 and 2007 was performed. Survival analysis was conducted using the Kaplan-Meier method. The independence of prognostic factors was analyzed using multivariate Cox proportional hazards modeling. The median age of patients was 68 years, and the average length of follow-up was 6.3 years. Perioperative mortality was 1.7%. The median survival was 6.5 years, with a 56% of the cohort surviving 5 years. Factors associated with poorer prognosis were male gender (hazard ratio [HR]: 1.30, p = <0.001), age (HR: 1.04 per year of increase, p < 0.001), limited resection (HR: 1.30, p = 0.002) tumor size (HR: 1.10 per 10 mm increase, p < 0.001), large cell histopathological cell type (HR: 1.35, p < 0.001), and positive resection margins (HR: 1.58, p = 0.002). T stage was a superior predictor of survival than tumor size (p < 0.001). There was no difference in survival by T-stage descriptor within stage T2 or T3. In surgically treated, node-negative non-small cell lung cancer, revised International Association for the Study of Lung Cancer staging criteria stratify survival well. Age, gender, and extent of resection are also important predictors of survival. Current T-stage descriptor groupings are appropriate.

SU-E-I-155: Esophageal Squamous Cell Carcinoma: Relationship Between 18F-FDG PET-CT Maximum Standardized Uptake Value, Metabolic Tumour Volume and TNM Classification

Purpose: The prognosis for patients with esophageal squamous cell cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade and cancer location. Few reports have discussed the relationships of both MTV and SUV max measured by PET/CT and stage in esophageal cancer, especially which classified by the last edition staging system. We aimed to evaluate the relationships between primary tumour maximum standardized uptake value, metabolic tumour volume and 7th edition American Joint Committee on Cancer (AJCC) classification in esophageal squmous cell carcinoma (ESCC) patients. Methods: Fluorine‐18 fluorodeoxyglucose positron emission tomography‐computed tomograhy (18F‐FDG PET/CT) scans of 41 consecutive newly diagnosed ESCC patients were retrospectively reviewed. Maximum standard uptake value (SUV max) and metabolic tumour volume (MTV) were recorded. Two‐tailed spearman's correlation was used to analyse the relationships between the metabolic parameters and AJCC stageing system. Results: Positive correlations were observed between SUVmax, MTV and N stage stage (P=0.002, R=0.477; P<0.001, R=0.563) in additon to AJCC stage (P=0.002, R=0.460; P<0.001, R=0.539). Both metabolic parameters were independent variables that significantly affected N stage and AJCC stage by the multiple analysis (P<0.001, adjusted R2=0.348; P=0.002, adjusted R2=0.238), and only SUVmax was independent variables that sinificantly affected T stage (P=0.003, R=0.459; P=0.004, adjusted R2=0.464). Conclusions: The metabolic parameters derived from 18F‐FDG PET/CT were positively correlated with T, N and AJCC stage in primary ESCC. Our findings may suggest a complementary role of these parameters to last 7th edition AJCC staging in prognostication of ESCC patients.

Staging of esophageal cancer: TNM and beyond

Previous staging of esophageal cancer was based on a simple, orderly arrangement of increasing anatomic T, then N, then M classifications. This system is consistent with neither data nor cancer biology. Recent worldwide collaboration has provided data for unique, modern machinelearning analysis that has resulted in a new, data-driven staging system for cancer of the esophagus and esophagogastric junction. This new system is presented in the seventh editions of the AJCC and UICC Cancer Staging Manuals. It is more representative of and consistent with the clinical reality of survival of patients with esophageal cancer. Changes address problems of empiric stage grouping and lack of harmonization with stomach cancer. In addition, for the first time, nonanatomic cancer characteristics such as tumor location, histologic grade, and histopathologic cell type are incorporated. The new era of data-driven staging of esophageal cancer promises a bright future for staging of all cancers. However, more extensive worldwide collaboration is required to refine and broaden TNM classifications and identify cancer and patient characteristics that influence esophageal cancer stage and impact survival.

Cancer of the esophagus and esophagogastric junction

Previous American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) stage groupings for esophageal cancer have not been data driven or harmonized with stomach cancer. At the request of the AJCC, worldwide data from 3 continents were assembled to develop data-driven, harmonized esophageal staging for the seventh edition of the AJCC/UICC cancer staging manuals. All-cause mortality among 4627 patients with esophageal and esophagogastric junction cancer who underwent surgery alone (no preoperative or postoperative adjuvant therapy) was analyzed by using novel random forest methodology to produce stage groups for which survival was monotonically decreasing, distinctive, and homogeneous. For lymph node-negative pN0M0 cancers, risk-adjusted 5-year survival was dominated by pathologic tumor classification (pT) but was modulated by histopathologic cell type, histologic grade, and location. For lymph node-positive, pN+M0 cancers, the number of cancer-positive lymph nodes (a new pN classification) dominated survival. Resulting stage groupings departed from a simple, logical arrangement of TNM. Stage groupings for stage I and II adenocarcinoma were based on pT, pN, and histologic grade; and groupings for squamous cell carcinoma were based on pT, pN, histologic grade, and location. Stage III was similar for histopathologic cell types and was based only on pT and pN. Stage 0 and stage IV, by definition, were categorized as tumor in situ (Tis) (high-grade dysplasia) and pM1, respectively. The prognosis for patients with esophageal and esophagogastric junction cancer depends on the complex interplay of TNM classifications as well as nonanatomic factors, including histopathologic cell type, histologic grade, and cancer location. These features were incorporated into a data-driven staging of these cancers for the seventh edition of the AJCC/UICC cancer staging manuals.

Prevalence of in vitro chemotherapeutic drug resistance in primary malignant pleural mesothelioma: Result in a cohort of 203 resection specimens

Optimizing the multimodality treatment of malignant pleural mesothelioma depends on many factors including an adequate chemotherapeutic response. Currently, chemotherapy regimens for patients with mesothelioma are empirically selected. In vitro chemotherapy resistance in human mesothelioma has not been reported. Our goal was to determine the prevalence of drug resistance in a large sample of malignant pleural mesothelioma using a commercially available assay. Tumors specimens (n = 203) were cultured for analysis of chemoresistance using the extreme drug resistance assay. Evaluable results were obtained in 168 (168/203 = 83%) specimens. Each specimen was tested with 3 drugs: cisplatin, gemcitabine, and vinorelbine. Drug resistance was characterized as low, intermediate, or extreme. Median age was 64 years (30-85 years). Forty-four (26%) patients received neoadjuvant chemotherapy before sampling and testing. The distribution of histopathologic cell types was epithelial (103; 61%), mixed (57; 34%), and sarcomatoid (8; 5%). A significant proportion of tumors had extreme/intermediate drug resistance to cisplatin (27%), gemcitabine (31%), or vinorelbine (59%). Nineteen tumors (11%) had extreme/intermediate resistance to all 3 drugs. Resistance (extreme/intermediate) to cisplatin was more prevalent in epithelial tumors than in nonepithelial (33% vs 18%; P = .0394). No significant differences in chemoresistance were found in tumors of patients who had received neoadjuvant chemotherapy compared with those who had not. The feasibility of performing off-site in vitro drug resistance assays on resected malignant mesothelioma specimens is reported. A significant proportion of mesothelioma tumors exhibited extreme/intermediate resistance to cisplatin, gemcitabine, or vinorelbine.

Optimum lymphadenectomy for esophageal cancer.

Using Worldwide Esophageal Cancer Collaboration data, we sought to (1) characterize the relationship between survival and extent of lymphadenectomy, and (2) from this, define optimum lymphadenectomy. What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals, analytic methodology, and generalizability of the underpinning data. A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration database. Patient-specific risk-adjusted survival was estimated using random survival forests. Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored. Optimum number of nodes that should be resected to maximize 5-year survival was determined by random forest multivariable regression. For pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+) cancers, 5-year survival improved with increasing extent of lymphadenectomy. In pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for pT3/T4. Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and >or=7 regional lymph nodes positive for cancer) and well-differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pT1, 20 for pT2, and >or=30 for pT3/T4 is recommended.